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j Jv miJr IVl tV i lL M~d INDUSTRIAL 
TOXICOLOGY 
BY 
ALICE HAMILTON, A.M, M.D. 
Assistant Professor of Industrial Medicine, 
Emeritus, Harvard University, 
Boston, Mass. 
AND 
RUTHERFORD T. JOHNSTONE, M.D. 
Formerly Assistant Professor of Medicine, University of Pittsburgh School 
of Medicine; Director of Department of Occupational Diseases, 
Golden State Hospital, California 
EDITED BY 
HENRY A. CHRISTIAN, A.M., M.D., LL.D., Sc.D. (Hon.), 
F.A.C.P., Hon. F.R.C.P. (Can.) 
Hersey Professor of the Theory and Practice of Physic, Emeritus, 
Harvard University; Clinical Professor of Medicine, Tufts 
College Medical School; Physician-in-Chief, Emeritus, 
Peter Bent Brigham Hospital; Visiting Physician, 
Beth Israel Hospital, Boston, Mass. 
[Reprinted from Oxford Loose-Leaf Medicine with the 
same page numbers as in that work~\ 
NEW YORK 
OXFORD UNIVERSITY PRESS Copyright, 1945, by Oxford University Press, New York, Inc. 
Printed in the United States of America FOREWORD 
A characteristic of American industry, a potent factor that has been re- 
sponsible for its great success in increasing production, improving the product 
and decreasing its cost, has been the continued development of new methods 
involving the utilization of hitherto unused, often hitherto unknown, materials 
and chemicals. Whenever a new material or chemical comes into use, considera- 
tion has to be given to its possible or probable effect on those in contact with 
it during the processes of its manufacture and in the subsequent use of the 
product. Is it in any way harmful to those who come into contact with it? 
Can this harm be prevented or so minimized as not to be a danger? What 
effects can be expected from any material or chemical newly introduced into 
industry? How can any injurious effects that may occur be recognized? 
What can be done to prevent them from causing injury? How should they 
be treated when they occur? These are questions that must be answered by 
those responsible for the health of workers and by those responsible for the 
health of those who will use the manufactured product. The physician 
of the worker often is the first to see evidences of injury to the worker. 
The subject of industrial toxicology, i.e., knowledge of injurious actions 
of substances used in industry, always has been important. Now with rapid 
changes being made in the methods of industry, this importance has been 
enhanced very greatly. Many physicians are confronted with the problems 
of the diagnosis and treatment of injuries and diseases developing in workers 
by reason of conditions associated with their work; this applies both to the 
physician employed by a given industry to care for its employees and to the 
general practitioner, who may be consulted by a worker. All of this makes 
very timely the publication of this concise volume on Industrial Toxicology 
written by Drs. Alice Hamilton and Rutherford T. Johnstone, who have 
had very extended experience in industrial toxicology as indicated by the 
data following their names on the title page of this volume. The editor be- 
lieves that this book will be found very useful' to many practitioners of 
medicine. 
Henry A. Christian 
Editor of Oxford Medicine CHAPTER XIX 
INDUSTRIAL TOXICOLOGY 
By ALICE HAMILTON and RUTHERFORD T. JOHNSTONE 
Table oe Contents 
Part I 
PATHOLOGY AND DIAGNOSIS 
By ALICE HAMILTON 
Introduction ' 600 
Inorganic Acids 604 
Sulphuric Acid and S02 604 
Hydrochloric Acid and Chlorine 605 
Nitric Acid and the Oxides of Nitrogen 606 
Hydrogen Fluoride and the Fluorides 608 
Chromic Acid and the Chromates 609 
Alkalies 609 
Barium 610 
Lead 610 (1) 
* Mercury 611 
Manganese 6r3 
Metal Fume Fever 614 
Cadmium 615 
Beryllium 617 
Magnesium 618 
Vanadium 619 
Zinc 619 
Antimony 620 
Copper 620 
Nickel . 621 
Silver 621 
Arsenic 621 
Arsine or Hydrogen Arsenide 623 
Selenium and Tellurium 625 
Phosphorus 625 
Phosphorretted Hydrogen or Phosphine 627 
Cyanides 627 
Acrylonitrile or Vinyl Cyanide 627 
Industrial Solvents . 628 
COPYRIGHT 1945 BY THE OXFORD UNIVERSITY PRESS, NEW YORK, INC. 
597 598 
CONTENTS 
Aliphatic or Petroleum Series of Solvents 629 
Alcohols 629 
Acetates 630 
Acetones: Ketones 630 
Aldehydes 631 
Glycols: Cellosolves: Dioxan 631 
Furfural 633 
Ether 633 
Metol 634 
Nitroglycerine 634 
Oxalic Acid 634 
Hexamethylenetetramine 634 
Acetylene 634 
Chlorinated Hydrocarbons 635 
Carbon Tetrachloride or Tetrachlormethane 636 
Trichlorethylene 639 
Tetrachlorethylene 642 
Ethylene Dichloride 643 
Tetrachlorethane 643 
Penta- and Hexa-chlorethane 644 
Methyl Chloride or Monochlormethane 644 
Ethylpne Chlorydrin 645 
Chlorinated Naphthalenes 645 
Bromine Compounds of the Hydrocarbons 647 
Aromatic or Benzene Series of Solvents 648 
Coal Tar Benzene or Benzol 648 
Toluene (Toluol): Methyl Benzene and Xylene (Xylol): Dimethyl Ben- 
zene .... 654 
Benzene Derivatives 657 
Aniline: Nitrobenzenes: Nitrotoluenes 657 
Dinitrophenol 659 
Dinitrocresol 660 
Paraphenylenediamine 660 
Chlorotoluidine 660 
Betanaphthylamine 660 
Trinitrotoluene: TNT 661 
Tetryl 662 
Chlor Compounds of Benzene: Nitrochlor 662 
Diphenyls 662 
Aniline Tumor of the Bladder 663 
Aniline Dyes 663 (1) 
Carbon Disulphide 663 (1) 
Synthetic Rubber 663 (5) 
Tobacco: Nicotine 663 (6) 
Radioactive Substances 663 (7) 
Carbon Monoxide 663 (10) 
Hydrogen Sulphide 663 (10-7) 
Petroleum Distillates 663 (10-9) 
VOL. IV. 445 CONTENTS 
599 
Part II 
TREATMENT AND PREVENTION 
By RUTHERFORD T. JOHNSTONE 
Foreword 663 (11) 
Sulphur Dioxide 663 (12) 
Chlorine 663 (13) 
Fluorine - 663 (14) 
Nitrous Fumes 663 (15) 
Welding 663 (16) 
Gases from Carbon Arcs 663 (17) 
Ammonia 663 (17) 
Mercury 663 (17) 
Manganese 663 (20) 
Chromium 663 (21) 
Metal Fume Fever 663 (21) 
Magnesium 663 (22) 
Arsenic 663 (22) 
Cadmium 663 (24) 
Zinc 663 (25) 
Selenium and Tellurium 663 (26) 
Vanadium 663 (27) 
Cyanides 663 (27) 
Carbon Tetrachloride 663 (29) 
Trichlorethylene 663 (31) 
Tetrachlorethane 663 (32) 
Methyl Chloride 663 (33) 
Ethylene Dichloride 663 (34) 
Chlorinated Naphthalenes and Diphenyls 663 (34) 
Alcohols: Glycols: Alcohol-Ethers 663 (35) 
Benzene (Benzol) and Its Homologues 663 (37) 
Phenol 663 (39) 
Nitrobenzene . 663 (40) 
Carbon Disulphide 663 (40) 
Butadiene 663 (41) 
Radium 663 (41) 
Lead 663 (43) 
Carbon Monoxide 663 (43-6) 
Hydrogen Sulphide 663 (43-7) 
The Petroleum Distillates 663 (43-8) 
Oxygen Therapy in the Acute Occupational Intoxications 663 (43-9) 
Part III 
Bibliography 663 (44) 
Vol. IV. 445 Part I 
PATHOLOGY AND DIAGNOSIS 
ALICE HAMILTON 
Introduction 
There are certain features in which industrial toxicology differs from general 
toxicology. These may be grouped under three heads, under the first of which 
would come the mode of entrance. In ordinary poisoning the usual channel is 
through the mouth; the poison is swallowed accidentally or intentionally. Next 
in frequency is the inhalation of poisonous gases, and the path through the skin 
is comparatively unimportant. In industrial poisoning the relative importance 
of the different paths of entrance is quite different. Inhalation of vapors, fumes 
and dusts is much the most important; then comes absorption through the skin, 
while the least important of all is ingestion through the mouth. 
Gases and vapors, which enter through the respiratory tract, are very numer- 
ous in industry. Some are compounds which have a direct local action on the 
tissues they reach. The heavy acids may act in this way when, through some 
accident, a spray of tiny droplets is thrown into the air. This is also the mode 
of action of the nitrogen oxides and of sulphur dioxide, all of which have a 
caustic action, which may be confined to the upper air passages or may involve 
the whole lung tissue. Other gases, without producing a local action, pass from 
the lungs into the blood. In this group belong the asphyxiating gases, CO, CO.,, 
HCN, H2S, the petroleum distillates and a large number of petroleum deriva- 
tives, benzene and its homologues. 
The most dangerous form of arsenic is not white arsenic but hydrogen ar- 
senide, which is given off in gaseous form, when one of the heavy acids, usually 
sulphuric, less often hydrochloric, comes in contact with an arsenic-bearing metal, 
zinc or iron, an accident not at all rare in industry. Mercury volatilizes at room 
temperature, and mercurial poisoning in industry usually is caused by inhaling 
volatilized mercury, although absorption may take place also through the skin. 
In poisoning from white phosphorus fumes are chiefly important, although the 
poison may be conveyed also to the mouth by phosphorus-smeared fingers. 
Metal fumes are finely divided particles of sublimed oxides produced by 
heated metals. These enter the body through the inspired air, and it is in this 
COPYRIGHT 1944 BY THE OXFORD UNIVERSITY PRESS, NEW YORK, INC. 
6oo INTRODUCTION 
601 
way that industrial poisoning from metals usually occurs. A similar danger is 
the inhalation of finely ground dust. 
Skin absorption is important chiefly in connection with the coal tar deriva- 
tives, aniline, the nitrobenzenes, the phenols, the compounds of toluene, of which 
trinitrotoluene is the most widely known. Others belong to the petroleum series, 
methyl alcohol, carbon tetrachloride, triorthocresyl phosphate and others, which 
produce industrial poisoning both through fume inhalation and through skin ab- 
sorption. Naturally it is difficult to decide just what part is played by the skin 
in the case of a volatile compound, because, whenever there is skin contact, there 
is also a possibility of fume inhalation, but with regard to the coal tar deriva- 
tives skin absorption seems decidedly the more important. 
Industrial poisoning by direct ingestion is of negligible importance. Paint- 
ers, white lead workers, makers of storage batteries may poison themselves by 
eating lead-soiled food or getting lead on their chewing tobacco, and it would be 
possible for men working with white arsenic or Paris green or the arsenates to 
be poisoned, if they eat with unwashed hands. Probably mercurial poisoning 
sometimes takes place in this way, but such cases are neither so common nor so 
severe as those that follow exposure to fumes or dust. 
A second difference between industrial poisoning and non-industrial is that 
the latter usually is acute, the former usually chronic. It is true that the occa- 
sional acute case of poisoning in industry attracts more attention, because it is 
startling, and it is clearly connected with the occupation, while the chronic case 
is not dramatic, and its connection with the occupation is often far from clear. 
Nevertheless chronic cases are not only far more numerous than acute; they are 
also sometimes more serious. Acute benzene poisoning is very rare nowadays, 
and if it does not kill, it almost never leaves behind a lasting injury, but chronic 
benzene poisoning occurs with much greater frequency and is far more serious. 
It is in the slow, chronic forms of mercurialism that we see palsies and psychoses, 
not in the acute, and the same is true of carbon disulphide poisoning. 
This is one reason why experiments on animals do not throw much light on 
the problem of industrial poisoning. The acute effects may be reproduced fairly 
easily but not the effects of tiny doses repeated throughout the years. 
The third important difference between ordinary toxicology and industrial 
is that the former usually deals with one poison at a time, while the latter often 
has to deal with a mixture of toxic bodies, which produce a complex and confus- 
ing picture. The temptation is to simplify, to pick out one poison and attribute 
all the symptoms to it, but error may lie that way. For instance, a case of brass 
poisoning may be very much complicated by the presence of lead in the alloy. 
Printers, who use type containing lead and antimony, and rubber compounders, 
who handle lead oxide and the sulphides of antimony, may, of course, suffer 
Vol. IV. 944 602 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
poisoning from either of these substances, but it seems hardly safe to diagnose 
a case of pure antimonial poisoning in such a workman and not to regard it as 
a mixed case. Even more puzzling is the problem with regard to the mixtures 
of volatile poisons, so much used in industry, the coatings, which contain mem- 
bers of the coal tar series and the fatty series, the paint and varnish removers, 
the dry-cleaning mixtures and the great • variety of compounds, which may be 
encountered in a single department of anilin dye manufacture. 
Finally, in considering industrial poisoning, it is necessary to remember that 
there are factors in industry which distinctly favor the action of toxic com- 
pounds by lowering the resistance of the body, increasing the possibility of ab- 
sorption or interfering with elimination. Heat and humidity help absorption 
through the skin and aid in the volatilization of the lighter poisons; heavy work 
increases the amount inhaled by increasing the depth of respiration. Long hours 
mean a larger dose of poison, for obviously a man can absorb more dust or fumes 
in ten hours than he can in eight. Since indigestion with constipation interferes 
with elimination, poor food becomes a factor of decided importance, and since 
absorption is much more likely to take place from a fasting stomach, the kind 
of breakfast taken by the workers in the poisonous trades becomes important. 
The British pay far more attention to the feeding of their work people than we 
do, and in the poisonous trades in England it is customary to provide a cup of 
milk or cocoa, free of cost, the first thing in the morning and to make it pos- 
sible for the workers to get a hot drink, usually tea with milk and sugar, in the 
middle of the forenoon and afternoon and an abundant hot meal at noon. In 
contrast to this a large number of American workmen in the poisonous trades, 
especially those of foreign descent, begin work in the morning on a breakfast of 
black coffee and bread and have nothing at noon but a cold, dinner-pail meal. 
The fact that individual susceptibility to poison varies very greatly is well 
known to toxicologists and always is clearly demonstrated in instances of mass 
intoxication, such as the famous methyl alcohol poisoning in a Berlin lodging- 
house from drinking adulterated brandy, when some men died after drinking a 
quantity of liquor which in others caused only a passing attack of headache and 
dizziness. In industrial poisoning this varying susceptibility is a very trouble- 
some factor and causes confusion in the mind not only of the employer but some- 
times of the industrial physician. So long as the majority of a working force 
escape the effect of a given poison, it is very hard to convince the employer and 
sometimes the physician that the man, who does suffer from its effects, has any- 
body but himself to blame. The employer argues that what is dangerous for 
one man must be dangerous for all, that a falling scaffold, a stream of molten 
slag, an electric current, produce the same effect no matter who is the victim. 
Therefore, if a dust or gas is harmful, all the men should suffer from it. He 
Vol. IV. 944 INTRODUCTION 
603 
always can produce some old and seasoned workmen, who have been with him 
for many years and have never been ill, and he does not see why he should 
be responsible for the weaklings who do fall ill. The industrial physician usu- 
ally argues that, if only a small proportion of the men react to a given poison, 
it means that those men are more uncleanly in their habits or are alcoholics, 
although a little investigation might prove to him that neither of these assump- 
tions had any basis. It is curious that men are so much more reluctant to ac- 
cept this fact of varying susceptibility toward industrial poisons than they are 
to accept the equally startling variation in susceptibility to infectious diseases. 
Nobody attempts to explain the cases that occur in an influenza epidemic on the 
ground of the personal habits of the victims. 
Aside from this purely individual variation, there are certain factors that 
influence the incidence of poisoning. How far race is a determining element we 
do not know. Legge and Goadby speak of a factory in which Italian workmen 
show considerably less susceptibility to lead poisoning than do their English 
comrades, but this lasts only so long as they adhere to their national diet and 
do not become addicted to alcohol. Negroes are considered by many practical 
men to be more susceptible to lead and less susceptible to poisons which enter 
through the skin, such as TNT, than white men, but it has never been possible 
to prove either of these theories, largely because it has not been possible to com- 
pare two groups, white and negroes, doing the same work and having the same 
living conditions. In our TNT manufacture and shell loading during World War I, 
it seemed at first that the negroes had decidedly less poisoning than the whites, 
but when both races had the same housing, ate the same food and used the same 
bathing facilities, the apparent difference between the two disappeared, and the 
negroes had their full share of TNT sickness116. The French experience with their 
munition poison, dinitrophenol, was much the same as ours with TNT. At first 
it seemed that the yellow race, the Annamites, were the least susceptible, and 
the whites were the most so. But when they took into consideration the different 
standards of personal cleanliness, the greater amount of alcoholism in the white 
group and also the greater skill in diagnosis of the men in charge of the whites, 
they were forced to the conclusion that racial susceptibility had very little to do 
with it (Perkins253). 
It is unquestionably true that youth and immaturity influence the incidence 
and the severity of industrial poisoning. This is recognized in all countries and 
embodied in legislation, wherever there is legislation for the protection of work- 
ers in the dangerous trades. Practically all European countries provide for the 
exclusion of boys and girls from occupations which expose them to poisons. In 
the United States such legislation has come more tardily, because it has never 
been the American habit to employ boys and girls in the poisonous trades, and 
Vol. IV. 944  INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
604 
the danger has existed in only a few industries, such as printing, type-founding, 
making lithotransfer paper, making lead seals, soldering and using volatile sol- 
vents. A committee representing the Federal Children’s Bureau has formulated 
a model law for the protection of youthful workers against occupational poison- 
ing, which it is hoped will be adopted by State legislatures. 
There is much vague evidence as to the greater susceptibility of women to 
industrial poisoning than men but little that is positive. With regard to lead it 
seems clear that women, if not actually more quickly poisoned than men (the 
two sexes rarely do exactly the same kind of work), are more subject to the 
severer forms of plumbism. As to the other poisons benzene is the only one 
concerning which it can be said with certainty that it is more dangerous for 
women than for men, this because benzene attacks the bone marrow, which is 
more labile in women than in men, and the hemorrhagic tendency in benzene 
poisoning is likely to cause in girls menstrual hemorrhage and in pregnant women 
abortion. 
Women are not more susceptible to the asphyxiating gases than men, but 
the war-time experience in England and in this country showed that young 
women suffered more from ether fumes than did mature men*7. The same im- 
pression holds in Germany with regard to the narcotic chlorinated hydrocarbons, 
especially trichlorethylene. Little is known about the effect on pregnancy of any 
industrial poison except lead and benzene, but mercury has been found in the 
fetal blood as a result of poisoning in the mother. 
Inorganic Acids 
Sulphuric Acid and S02 
Sulphuric acid is the most important industrially of the inorganic or “ heavy ” 
acids, but it is rarely the source of injury to workmen. Its action is on the 
upper air passages, but bronchitis and bronchopneumonia have not been traced 
to such fumes. 
Sulphur dioxide is formed in the course of many industrial processes, smelt- 
ing sulphide ores, synthetic production of phenol, production of sulphuric acid 
by the chamber process #, refrigeration, bleaching paper, burning coke. To' the 
ordinary person S02 is almost irrespirable, but men become accustomed to it 
fairly easily and carry on in an atmosphere, which is choking and painful to a 
# This is the older and cheaper process, roasting iron sulphide or sulphur or iron filings 
from gas works. In addition to the S0o fumes there is danger from nitrogen oxide gas which 
provides an extra atom of oxygen. It is this last that must be held responsible for “ gassing ” 
in men who clean sludge from the chambers (see also section on Arsenic). Contact acid is 
made by the use of a catalyst to effect the final oxidation. 
Vol. IV. 944 INORGANIC ACIDS 
605 
visitor. A dangerous amount in the air sets up a violent reflex which forces the 
man to escape, and if he cannot, bronchitis, bronchopneumonia, edema of the 
larynx and lungs may follow. 
An accident was reported to one of us (A.H.) involving some 13 men, who 
were shovelling sulphur from the hold of a vessel, when a spark from a travelling 
belt ignited the sulphur dust in the air and filled the place with S02. Those who 
were near the exit from the vessel’s hold suffered no serious harm, but two men 
far back in the ship lost their way, and by the time they were brought out, they 
had breathed enough gas to set up severe bronchopneumonia with incapacitation 
for some two months. 
The use of S02 as a refrigerant has led to accidental poisoning but in our 
experience not of a serious nature. For instance two cases seen by one of us 
(R.T.J.156) were in men who were in a small enclosure where a drum of S02 
exploded. Their clothes froze at once, and one of them had his right eye frozen, 
but it returned to normal in four weeks. The other presented a picture typical 
of bronchial asthma, but after 30 hours the lungs were clear, and he went back 
to work at the end of four days. 
Gordon93 reported recently an interesting form of S02 poisoning, following 
exposure to the gas from a refrigerator. The immediate irritation died down 
promptly, but five days later an acute tracheobronchitis developed with a thick, 
gray membrane which was removed, but the symptoms were slow in clearing up. 
Three months later he returned to work, inhaled S02 again, this time from the 
fumes of coke, and developed a second attack which ended in a partial stenosis 
of the left main bronchus. 
Chronic poisoning from S02 does occur, but apparently it is not common. 
Haggard111 believes that immunity is not acquired, that the cessation of irrita- 
tion to nose and throat comes from a chronic catarrh which produces a tenacious 
mucus as protective covering for the upper air passages but not for the lung tissue. 
Kehoe160 studied the effect of long and heavy exposure on ioo men and found 
a high incidence of slight nasopharyngitis, alteration of the sense of taste and 
smell, dyspnea on exertion, increased fatigue, abnormal reflexes and abnormal 
urinary acidity. 
Hydrochloric Acid and Chlorine 
Hydrochloric acid gives practically no trouble in industry, but its anhydride, 
chlorine, is notoriously dangerous. 
Chlorine is a greenish yellow gas intensely irritating and damaging to all 
mucous surfaces and to the conjunctiva. We know of its effects chiefly through 
its use in World War I, but industrial cases are almost never as severe as war 
cases were, for in war the men could not escape the gas; in industrial work the 
VoLo IV. 944 606 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
victim knows he is breathing a poison and escapes as quickly as possible. In 
ordinary cases there is a temporary disability with inflamed throat and burning 
“ deep in the chest ” and rarely pneumonia or acute congestion with edema. 
Chlorine is produced by electrolysis of common salt and sold in containers, the 
accidental leaking of which is the source of most of the cases of gassing. 
Phosgene: COCl2 belongs under this heading, since it breaks up and forms 
hydrochloric acid when it comes in contact with the moisture of mucous sur- 
faces (Hegler131). The special danger of phosgene gas is its non-irritating char- 
acter, for it does not give warning by a strong reflex, as do chlorine and hydro- 
chloric acid. It is used as a dye intermediate and may be produced by the heat 
decomposition of carbon tetrachloride and other chlor compounds, chiefly when 
they are used as fire extinguishers58 but also when for any reason the fumes 
come in contact with a naked flame. McNally2’13 reports such a case with symp- 
toms of trichlorethylene intoxication, to which was added acute congestion of the 
throat and lungs. 
Nitric Acid and the Oxides of Nitrogen 
The manufacture of nitric acid and its use in various industrial processes are 
attended with danger, for the escape of the acid to contact with the air results 
in the evolution of nitrous and nitric oxide fumes which have a decidedly caustic 
action on the respiratory tract. Haggard111 has pointed out that all respiratory 
irritants have the same toxicological action. The difference in symptomatology 
is related to the location of their action and is dependent upon the relative solu- 
bility of the irritating gases. A gas that is very soluble in water is readily taken 
out of the inspired air by contact with the first moist tissue it reaches. Hence, 
the upper respiratory tract bears the brunt of action. A gas that has a low 
solubility in water is slower to liberate its irritant principle, and the main dam- 
age occurs deeper in the respiratory tract. Here nitrogen oxide fumes belong, 
for their action on the nose and throat is less irritating than that of chlorine or 
S02. Therefore, they do not give warning of danger to the same degree. 
During World War I the accidental escape of nitrous fumes was fairly com- 
mon, because engineers were not yet familiar with the difficulties encountered in 
its production and use. It is almost impossible to avoid leaks, the acid eating 
through almost every known substance. The production of high explosives by 
nitration of cotton, paper, glycerine and starch is attended with the sudden 
formation of nitrous fumes in the presence of water, or if the temperature is too 
high. Nitric acid is made by the action of sulphuric acid on sodium nitrate, 
Chili saltpeter or more rarely, on ammonium nitrate, if atmospheric nitrogen is 
being used. It is used to make the high explosives, smokeless powder and mili- 
Vol, IV. 944 INORGANIC ACIDS 
607 
tary gun cotton, nitroglycerine and nitrostarch (Trojan powder), nitrocellulose 
for celluloid, photographic films, lacquers, “ dopes ”, etc. for etching metals, for 
various processes in the making of coal tar dyes and drugs and for preparing 
metals for coating. It is produced accidentally in mines, when the blasting pow- 
ders burn instead of detonating, or in blasting for tunnelling (Irvine151). The 
increasingly important work of autogenous welding has brought a new source 
of nitrous fumes, for under the intense heat of an oxyacetylene or electric torch 
the oxygen and nitrogen of the atmospheric air unite to form oxides of nitrogen. 
The action on the respiratory tract is caustic, and there is congestion of the 
throat, which may result in edema of the glottis, congestion of the bronchi, which 
may be extreme, and, if the finer bronchi are involved extensively, there is in- 
creasing dyspnea, the lungs fill with exudate, and death may come on rapidly 
from edema of the lungs (Wood348). Slower cases develop pneumonia, some- 
times not till some days after the accident (Hall and Cooper113), or there may 
be an acute inflammation followed by a fibroid process, bronchiolitis obliterans 
(Fraenkel82), or by tuberculosis. In case the exposure is very great, death may 
come on within a few hours or even minutes, and the only significant finding at 
autopsy may be the presence of nitric acid in the blood115. Several such cases 
occurred during the early years of World War I, when conditions in industries 
sometimes were extremely primitive. The blood in nitric acid poisoning is thick, 
sticky, tarry, with diminished alkalinity (Doremus and McNally54) or acid from 
the presence of nitric acid. The studies made of the victims of the Cleveland 
Clinic fire showed that this thickening is not inspissation of the blood, for there 
is no loss of serum, but is due to an increase in erythrocytes under the stimulus 
of the pulmonary edema and consequent anoxemia (Muntwyler and Associates231 
and La Towsky and Associates180). 
The following history from a guncotton plant in 1917 is typical of nitrogen 
oxide poisoning (A.H.). A man was working in the nitration shed, producing 
military gun cotton, which requires 100 per cent, nitric acid. A centrifuge blew 
up, and the heavy lid knocked him senseless. The other men fled at once but 
did not miss him immediately, so that he was exposed to the fumes for some 
minutes before they dragged him out. Still, when he came to in the fresh air, 
he did not feel that he had been injured, and after the then usual first-aid treat- 
ment, a few drops of chloroform in water with aromatic ammonia to quiet the 
spasmodic cough, he went home. During the night he woke, feeling he was being 
strangled, and when the physician saw him, he was propped up in bed, his face 
livid and terror stricken, his air hunger increasing, unable to speak or move. He 
had complained earlier of gastric pain, but that was submerged by his air hun- 
ger. In spite of a rather tardy administration of oxygen he died of edema of 
the lungs in less than 24 hours after the accident. 
Vol. IV. 944 608 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
The American Standards Association has set 2 5 parts per million as the maxi- 
mum allowable concentration of oxides of nitrogen*. 
Hydrogen Fluoride and the Fluorides 
This very corrosive acid, hydrogen fluoride, sometimes is used instead of 
sandblasting for preparing metal for coating by “ pickling ”, for cleaning sand- 
stone and marble, removing porcelain enamel, frosting glass. It has displaced 
the sandblast also in frosting electric light bulbs. The effect is that of a power- 
ful caustic. 
An unusual case of injury from hydrogen fluoride was the following (R.T.J.): 
A man, who had fallen and broken a small bottle of the acid, had received 
splashes on face, hands, left arm and left thigh and, half an hour later, was ad- 
mitted to the hospital with burns of a second degree in all these areas, but the 
fingers of the left hand were blanched, at first, then soon grew dusky. The next 
morning they were gangrenous, and eventually all the distal phalanges had to 
be amputated. 
A new use for hydrogen fluoride has come to light recently, as a catalyst in 
the production of high octane aviation fuel. This is said to provide a very diffi- 
cult problem for safety engineers. 
Fluorides are used in smelting steel and aluminum and are given off in the 
production of superphosphate from phosphate rocks. Most of the cases of fluor- 
ism have come from the recovery of aluminum from cryolite195. 
The French were the first to describe “ fluorisme ” or cachexia fluorica as 
seen in miners of cryolite, a double fluoride of sodium and aluminum with some 
54 per cent, fluorine (Feil72). The chief characteristic of this form of industrial 
poisoning they found to be sclerosis of the bones, resulting from the fixation of 
calcium by fluorine. Soon after this Moller and Gudjonsson1425 made the same 
discovery in Swedish miners and Roholm265 published an exhaustive study of the 
bone changes, thickening of the bone laminae, opacity of the bones by x-ray and 
calcification of the ligamental attachments. The appearance in roentgenograms 
is said to have been noted first by Moller in 1931 in the course of an examina- 
tion of cryolite miners for silicosis. 
* A committee, Z37, of the American Standards Association for some years has dealt 
with the task of determining the “ maximum allowable concentration ” of the most important 
industrial poisons. When mention of such a standard is made here, it must not be forgotten 
that these are calculated on the amount of air inhaled by a worker, when breathing at an 
ordinary rate, for eight hours. Heat and heavy work increase both the rate and the depth of 
respiration and so hasten the absorption of the poison. Zangger of Zurich, an authority on 
volatile poisons, says there is always more trouble from their use in hot weather and in southern 
climates. .American experience confirms this abundantly. Of course heat also favors the 
evaporation of a solvent. 
Vol. IV. 944 ALKALIES 
609 
Roholm265 describes chronic fluorisme as having clearly defined diagnostic 
signs, mottled enamel of the teeth, osteosclerosis and osteomalacia. In addition 
one should look for general symptoms, anorexia with loss of weight, anemia, per- 
haps from encroachment on the bone marrow, and cachexia. He found diffuse 
osteosclerosis in 84 per cent, of the workers in cryolite, but Brailsford21 examined 
49 Scotch cryolite miners exposed for many years and found no sign of it. 
According to Brun and his colleagues25 cryolite workers excrete fluorides in 
large quantities in the urine for some years after exposure has ceased, probably 
from breaking down of pathological bone tissue, for such men show less osteo- 
sclerosis than do working miners. They believe that daily intake of as much as 
28 mgm. over many years is needed to produce osteosclerosis. 
One of the few American studies of “ fluorosis ” in man is that of Bishop14, 
who was examining a group of 78 cryolite miners for possible silicosis. Thirty- 
nine of them showed evidence of first or second degree silicosis, and over half of 
these presented definite bone changes in roentgenograms, varying from a “ fleecy 
thickening of the bone lamina and an increase in the whiteness of the bone 
shadows to an actual opacity of the bones and calcification of the ligamentous 
attachments 
Chromic Acid and the Chromates 
Chromic acid and the chromates present problems to the engineer more than 
to the physician. Chrome ulcers, known as chrome holes, form on the skin and 
may penetrate deeply, but they are not very painful, and they never suppurate, 
the acid apparently acting as an antiseptic. Nor has there ever been a case of 
epitheliomatous degeneration reported, although thousands of chrome ulcers have 
been observed in England and in Germany. The lesions caused by chromium 
compounds are characteristic and visible, which is probably the reason why this 
form of occupational poisoning has attracted much more attention and is sur- 
rounded by a much greater degree of protection than its importance deserves. 
Aside from the skin ulcers there is involvement of the nasal mucosa with chronic 
inflammation, a purulent discharge, the formation of crusts and some difficulty 
in breathing but rarely much more than that. Ulcers then form, painless and 
slow, confined to the cartilagenous portion of the septum and ending in perfora- 
tion but never in deformity (Blair15, Bloomfield and Blum16, Dixon52). The 
American Standards Association has suggested i mgm. per io cu. meter as the 
maximum allowable concentration for chromic acid and the chromates. 
Alkalies 
The alkalies used in industry are numerous, and some of them are very power- 
ful caustics, while all have more or less caustic action on the skin. They present, 
Vol. IV. 944 610 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
however, no problem to the industrial physician, for their control is a matter of 
engineering skill and good plant practice, and the lesions produced are evident 
to all. The National Safety Council has prepared several pamphlets on the safe 
handling of caustic alkalies and the best method of treatment of alkali burns. 
The fact that ammonia is a gas makes it more dangerous in industry than are 
the solid caustic hydrates. Accidents from the bursting of an ammonia supply 
pipe in a refrigerating plant occur from time to time, the severity of the effect 
depending on the time that elapses before the victims can escape. Legge says 
that there were reported in Great Britain between 1920 and 1931 74 cases of acute 
poisoning from ammonia fumes, all accidental, and most of them caused by leaks 
or breaks in refrigerating plants and in plants recovering nitrogen from the air183. 
According to Henderson and Haggard136 irritation from ammonia fumes begins 
at 0.5 mgm. per liter of air, coughing at 1.2 mgm., but for prolonged exposure 
the limit should be 0.07 mgm. It is, however, a matter of common knowledge 
that men become accustomed to the fumes to a considerable degree (Flury and 
Zernik80). Both Lehmann and Seifert (see ref. 66) found it impossible to produce 
chronic poisoning in animals, but Ronzani267 claims to have set up not only con- 
junctivitis but keratitis and also a loss of hemoglobin and a lowered resistance to 
infection, while Horvath141 goes even further and believes that pleurisy and 
bronchopneumonia follow the repeated exposure of animals to low concentrations 
of ammonia. 
Aside from refrigerating plants and the manufacture of refrigerators, am- 
monia fumes may be encountered in storage battery manufacture and in rubber 
vulcanization, but the fumes are not excessive. Thies314 says that as long as ten 
days after an accidental injury to the eye from splashing of ammonia water a 
severe conjunctival and corneal ulcer may develop, and he describes such a case. 
Barium 
Men handling large quantities of barium compounds, the sulphide, oxide, 
carbonate, sometimes complain of irritation of the throat and nose and eyes, 
for the dust is somewhat caustic. Bertarelli13, however, who has written one of 
the few articles on the possible action of barium compounds in industry, says he 
has never seen any sign of toxic symptoms in workers exposed for long periods 
to barium chloride. It seems that in Italy this compound is used in treating wool 
for stuffing mattresses, and carding this wool is dusty work, yet no harm seems to 
result from it. On the other hand Kipper163 has described a fatal case of poi- 
soning from barium oxide and succeeded in producing in animals paralyses and 
an effect on the heart like that of digitalis. Occupational dermatitis from barium 
compounds unquestionably does occur. 
Vol. IV. 944 LEAD 
Lead 
Lead is looked upon universally as the industrial poison par excellence because 
of its widespread use, its characteristic effects and the great mass of data con- 
cerning it collected from all industrial countries throughout more than a century 
of study. The lead compounds encountered in industry are, in the order of their 
importance, the suboxides, litharge and red lead, the basic carbonate or white 
lead, the basic sulphate or sublimed white lead, the chromate, the sulphate and 
carbonate, the sulphide, lead tetraethyl and less commonly, the acetate, nitrate 
and chloride. A large number of industries use metallic lead in molten or solid 
form, and as this oxidizes rapidly, the workmen are exposed to the lower oxides 
of lead, which form a coating of finely divided gray powder on the surface of solid 
metal and an easily detached coating of so-called dross on the surface of molten 
lead. 
These compounds differ decidedly in their toxicity, an important point in the 
prevention of lead poisoning in industry. It is not nearly so necessary to guard 
against dust in the lead mines of Missouri, where the ore is lead sulphide, very 
slightly soluble in human gastric juice (see Carlson and Woelfel33a), as it is in 
the mines of Utah, which carry the much more soluble carbonate and sulphate. 
Lead glaze for pottery gave rise to much plumbism so long as raw white lead, 
the basic carbonate, was used, but when the white lead was changed by fritting, 
i.e. fusing and granulating, to the insoluble disilicate, that danger disappeared. 
The toxicity of a given lead compound depends on (a) the solubility in the 
body fluids and (b) the fineness of the particles, for the finer they are, the more 
quickly do they dissolve. A lead compound such as the acetate, for instance, 
which when swallowed is very toxic, may be industrially harmless because it is 
sticky, not dusty. 
Various estimations of the relative toxicity of these compounds have been 
made. Fairhall71a recently published the results of exhaustive tests on animals 
to determine the relative toxicity of the most important lead compounds. From 
inhalation experiments on guinea pigs he concludes that, while no exact numerical 
order can be assigned to the various compounds, certain of them may be set 
apart as more toxic than others. Thus the carbonate, monoxide and sulphate 
seem more toxic than metallic lead or other compounds. Lead arsenate is very 
toxic, but this is due to the arsenic radicle. The chromate is less toxic. 
Some twenty years ago an effort was made in this country and in England 
to press the use of “sublimed white lead”, which is the basic sulphate, in the place 
of “old Dutch process white lead”, the basic carbonate, on the ground that the 
former was non-poisonous. Carlson and Woelfel33a tested the solubility of the 
two in human gastric juice and found that the basic sulphate is soluble, averaging 
24.7 to 30.0 per cent., while the basic carbonate averages 59.8 to 77.9 per cent. 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Later the same question arose in Germany and led to several investigations of 
the claim that the sulphate is a safe pigment. Lehmann185a and Koelsch and 
associates169b fed animals with the two compounds, and both found little, if any, 
difference in their toxicity. 
Lead borosilicate, present in fritted ceramic colors, is insoluble in water, but 
Beebe and Mallette12c have shown that it can be found in the liver and skeleton 
of animals exposed to a spray mist of colors such as are used in industry. The 
new explosive, lead azide, was tested by Fairhall and associates710, who found that 
absorption and distribution are the same as for other lead compounds, but the 
acute toxic action is caused by the azide radicle rather than the lead. It is de- 
cidedly less toxic than sodium azide. Lead acetate, nitrate and chloride are all 
highly soluble, even in water, but fortunately they do not form dust readily, nor 
are they industrially important. 
Lead tetraethyl differs from all the other forms of lead, which are used in- 
dustrially, in that it is volatile and highly soluble in lipoids and, therefore, acts 
markedly on the central nervous system. It is also the only lead compound which 
is known to be absorbed through the skin. 
The industries in which lead is produced or used are too numerous to list, 
and the majority are too well known to make this necessary. It may be well to 
emphasize a few points in connection with its industrial use which are not so 
generally known. For instance the danger of contamination of the air from 
molten lead does not start at the temperature at which lead vaporizes, but at 
a much lower point, for whenever molten lead is agitated, as in skimming off 
dross, dropping in pigs of lead, ladling and pouring, the delicate coating of grey 
suboxide is detached and floats up with the waves of heat. This is the greatest 
source of plumbism in printers, for such fumes may come from the remelting 
kettles, the monotype and stereotype machines, though apparently not from 
linotypes. In a study of Virginia printing plants recently Homewood and 
Worsham140b found the lead in the air to be within allowable limits except in 
drossing and sieving when as much as 955 mgm. per 10 cubic meters was found. 
It is the suboxide, too, that is produced by the use of the oxyacetylene torch 
on lead or lead-painted surfaces as in the scrapping of battleships before the war 
and in welding lead painted ships at the present time (Brown22d, Tabershaw306b, 
Kehrlein160c). It is also the suboxide, which constitutes the danger in using solder, 
either by hand or machine (Lea and Fluck180c) and in founding brass or “ railroad 
bronze”, which may contain over 25 per cent, lead and is poured at about noo° C. 
(Pedley and Ward249). Although soldering usually is regarded as a fairly harmless 
job, I have the history of a man in the Mayo Clinic, who after three years of such 
work developed a typical attack of lead colic, and shortly thereafter both wrist 
and ankle drop and “definite evidence of lead encephalopathy”. The danger 
of lead fumes and lead dust in brass foundries has been mentioned under “Metal 
Vol. IV. 445 LEAD 
Fume Fever”. The suboxide forms over the surface of solid lead, though much 
more slowly than it does on molten lead. This must be guarded against in 
printing plants and in all places where metallic lead is handled. 
The chief uses for white lead, the basic carbonate, often called old Dutch 
process white lead, are for paint and for pottery glazes and ceramic colors. Much 
less white lead is used in house painting nowadays. Even in outside paint the 
white lead is tempered with harmless titanium oxide, and interior work usually 
is done with lead-free paint. In earlier years lead paint was used for all vehicles, 
from carriages to Pullman cars; now that is all gone. 
The painters’ work, which used to be a notorious source of plumbism, witness 
the phrases “ painter’s colic”, “ painter’s palsy”, is now fairly free from this dan- 
ger, sometimes wholly free. A lessening of the danger of plumbism for potters 
also has come in the general adoption, learned from the English, of fritted lead 
glaze containing almost insoluble lead silicates. The extremely fine particles of 
ceramic colors contain borosilicates which are somewhat more soluble. 
Litho transfer preparation consists in spreading very finely ground lead colors 
on specially prepared paper. It is recognized everywhere as very dangerous work 
and commonly employs young women. 
The oxides, litharge, red lead and the brown peroxide, are not so soluble as 
the basic carbonate, but they are very dusty, and it is hard to control air con- 
tamination wherever they are used. It is these three oxides that render the 
making of storage batteries the most prolific source of plumbism at the present 
time. Litharge finds extensive use in glazes and enamels but no longer in rubber 
compounding. Red lead paint has come back during the war, especially in ship- 
building. Red lead still is used in the enamelling of sanitary ware but far less 
than formerly. 
Tetraethyl lead is added to motor fuel gasoline in the proportion of one part 
to 1,300 parts of gasoline, and an organic halogen, usually ethylene dibromide 
(Humperdinck142a), is added also in order to help in the removal of lead from 
the engine. When it was first produced and blended with motor fuel, there was 
general ignorance of its dangerous nature and of the ease with which it is ab- 
sorbed by the human body. It was handled recklessly by experimental chemists 
as well as by ignorant workmen, and as a result there were cases of acute poison- 
ing of a peculiarly severe type. Eldridge of the Chemical Warfare Service 
published in October 1924 the records given him by Thompson and Schoenleben316a 
of severe and fatal poisoning. Kehoe160b added records of milder forms, making 
some 139 cases in all with 13 deaths. 
The result of these dramatic occurrences was a fear of danger to 
garage workers and even to car users, if the gasoline contained tetraethyl lead. 
Zangger of Zurich demanded that its use be forbidden in Switzerland, and the 
same demand was made in Britain and in some states of the United States. Since 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
an impartial inquiry was called for, Surgeon General H. S. Cumming appointed 
a committee of experts to supervise such an inquiry and assigned members of the 
Public Health Service to carry it out. The findings were that garage workers 
exposed to tetraethyl lead showed evidence of lead absorption and storage but 
not of intoxication; chauffeurs who had used it for two years did not show even 
absorption (Leake180d). The danger to producers and blenders had been con- 
trolled already. 
Since then, Kehoe and his colleagues16013 have followed all reported cases of 
tetraethyl lead poisoning and have kept under observation some 300 men, who 
have incurred unusually severe exposure to leaded gasoline for some years. These 
men were examined for physical fitness and signs of lead absorption or intoxica- 
tion, but no such evidence was found. Kehoe’s findings were confirmed by the 
animal experiments of Kraut and Lehmann173b. 
A secondary danger in connection with the use of leaded gasoline, namely the 
carbonized products found in the engine, is described by Waniek322*. These 
products may give rise to the more common forms of plumbism, masking the 
cerebral symptoms of tetraethyl. Kehoe lays stress upon this fact and upon the 
danger incurred when workmen must clean sludge from storage tanksl60b. 
The latest publication on this subject is that of Mortensen229'1, who studied 
the absorption of tetraethyl lead with radio-active lead as indicator. He found 
that 16 to 23 per cent, of the lead, which reaches the alveoli, passes into the blood. 
The lethal dose was found to be from 8.9 mgm. per kgm. with survival of four 
days to 30.1 with survival of four hours, which is smaller than Buck and Kumso’s25a 
figures, 16 mgm. injected into the peritoneum and Kehoe’s, 22 mgm. injected 
into the veins. He found, as did Kehoe and Thamann160u, that lead tetraethyl 
is destroyed quickly in the body. Volatile lead disappears from brain, viscera 
and blood in a few hours. 
In considering industrial lead poisoning, it is very important to keep in mind 
the kind of exposure which is present in different lead jobs. Some involve ex- 
posure to very small quantities, which if continued over many years, may lead to 
chronic intoxication but would very rarely give rise to an acute and severe case 
of poisoning. Examples of these are most of the processes which use metallic 
lead, the printing trade, making lead pipe, wire, grids, etc., the plumbers’ trade. 
On the other hand severe, acute cases may occur wherever dust and fumes are 
excessive as in smelting and refining, the production of white lead, roasting 
oxides, sandpapering, chipping or burning lead paint, making storage batteries, 
etc. Colic, palsy, encephalopathy may develop rapidly in such a plant, if pre- 
cautions are neglected. 
The entrance, absorption, storing and excretion of lead were described by Aub 
and his colleagues413’5,6a on the basis of three years of experimental and clinical 
studies carried on at Harvard between 1923 and 1926. These investigators found 
Vol. IV. 445 LEAD 
that if lead were given by stomach tube to cats it would be found chiefly in the 
feces because ingested lead is only partially absorbed, and the greater portion of 
the fraction that is absorbed is caught by the liver, part of it being then reexcreted 
into the intestinal tract with the bile. Therefore, much of the lead that enters 
the gastrointestinal tract does not really enter the organism at all, but either is 
eliminated directly or never passes beyond the liver. When lead is administered 
in this way, very large doses are needed, and the administration must be con- 
tinued for weeks in order to produce symptoms of intoxication. On the other 
hand, if lead is given by way of the respiratory tract, severe symptoms appear 
quickly. There is no such defensive system in the respiratory tract, and absorp- 
tion takes place easily not only from the alveoli of the lungs but from the mucous 
surfaces of the air passages, beginning with the nostrils (Blumgart17a). Therefore, 
the great danger in lead occupations is the presence in the air of lead dust and 
fumes, the latter being really very finely divided particles of dust. Modern 
experience has amply confirmed the dictum of Tanquerel des Planches a century 
ago that severe plumbism never follows the handling of solid lead but only ex- 
posure to dust and “emanations”. 
This is a very important fact, especially in connection with the prevention of 
lead poisoning, for unless dust and fumes are controlled, no degree of personal 
cleanliness will avail to protect the worker against poisoning. Some 20 years ago, 
before industrial hygiene had made much progress in the United States, it was 
possible for one of us (A.H.) to collect histories of 132 cases of that very severe 
and now rare form of plumbism, lead encephalopathy. All the victims of the 
acute form had had excessive exposure to dust or fumes. 
The signs and symptomsih,5 of acute lead poisoning usually are referable to 
either the gastrointestinal tract or the nervous system, although we sometimes 
see cases involving both. There are usually more marked prodromal symptoms 
than in the chronic cases. These consist in a disagreeable sweetish taste in the 
mouth, anorexia, nausea, sometimes vomiting, headache which may be severe, 
disturbed sleep, lassitude and a sense of weakness which is general not localized. 
Constipation is very common and may be interrupted by diarrhea due to the 
gastroenteritis so often present in acute cases. After a few days of general malaise 
and constipation and colicky pains the patient may develop sudden, severe colic. 
In typical cases colic is accompanied by a rigid abdomen, marked pallor of the 
skin, an increase in blood pressure and a slow, hard pulse. The constipation 
usually is obstinate during colic, and there is nausea and vomiting. Such an 
attack may pass over in a few hours or last several days. 
“ Encephalopathia saturnina” is used by Westphal327a as the term to cover all 
affections of the brain due to lead such as apoplexy, hemiplegia or aphasia from 
saturnine arteriosclerosis, coma, delirium, epileptiform convulsions, lead hys- 
teria, lead mania, lead neurasthenia. 01iver244a restricts the term to epilepti- 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
form convulsions caused by lead, in which he is generally followed, although 
von Jaksch1533 would reject the term altogether and substitute more precise 
terminology such as encephalitis, epilepsy, mania saturnina, etc. French authors 
have reported many cases of lead meningitis, which probably in other countries 
have been included under the general term of encephalopathy1913’229c. 
This is fortunately a rare form of plumbism nowadays, although occasionally 
a case is reported in this country or abroad. It may take the form of intense 
headache, then delirium, convulsions, coma, followed sometimes by permanent 
mental impairment or by blindness partial or total, or it may be a slowly pro- 
gressing, mental deterioration resembling that of general arteriosclerosis and 
accompanied by a contracted kidney (Westphal3273, Osler245b). A lasting epilepsy 
followed an acute cerebral plumbism in a case described by Putnam2623, and a 
similar one was seen by one of us (A.H.). Injury to one or more of the cranial 
nerves has been attributed to lead by many authorities. In the United States 
lead blindness seems to be a great rarity, but in English potteries in the days 
before strict regulations were enforced Prendergast2613 found among the cases of 
plumbism in women potters 7.7 per cent, with total and 10.2 per cent, with partial 
loss of vision. 
Pain in the joints, lead arthralgia, is fairly common and in rare cases may be 
the most prominent symptom. In Tanquerel’s 1,217 cases there were 201 which 
belonged in this class. 
Lead palsy is usually a late occurrence, developing slowly, and it is not ac- 
companied by neuritic pains as is the palsy of arsenic or alcohol. It tends to 
recovery, if exposure is stopped in time. The localization according to the gen- 
erally accepted theory of Edinger is determined by the use of muscles; those 
most fatigued are the most affected. Modern industrial work calls chiefly 
on the extensor muscles of wrist and fingers, which are not as strong as the 
flexors and are working against gravity. Therefore, the typical form of lead 
palsy is wrist and finger drop, but in children and in heavy workers it is ankle 
drop. 
Lead gout is described by German authors, but neither American nor British 
authors lay stress on it. 
That lead is a race poison causing sterility, miscarriage, stillbirth in women 
has been known for centuries, and the carefully gathered statistics of Oliver2443 
and of several French physicians (see reference no. 117 p. 171) give abundant proof 
of the harmful action of lead on the germ cell, on the chorionic epithelium or on 
the fetus through the mother’s blood. It is not so well known that lead may pro- 
duce sterility in the male also by injury to the germ cell, but this fact, which was 
first brought out by Constantin Paul247a in i860 and more recently by Koinuma1703 
in 1926, is established now beyond doubt. It has been used as an argument against 
laws providing special protection for women in lead work, but that ignores the 
VOL. IV. 445 LEAD 
nine months of intrauterine life during which the fetus may receive lead from 
the mother’s blood. 
The diagnosis of lead poisoning after decades of study still is a subject of 
controversy, for though a typical case in a lead worker offers no difficulty, there 
is an endless variety of forms which this mode of poisoning can take. To sum up 
the problem briefly, the physician must prove first exposure to lead, second 
absorption, third intoxication. The first depends on a careful occupational his- 
tory, the second on evidence that lead has entered the body, the third on evidence 
that the lead has produced injury to the body. 
It is important in these days of legal responsibility for cases of occupational 
poisoning not to confuse evidence of absorption with proof of intoxication, for 
the latter must include clinical signs and symptoms of actual illness. Absorption 
of lead is shown by its presence in the blood and in the excreta and by its effect 
on the blood cells. To take the last first, the change in the red blood corpuscles, 
which consists in the appearance of fine blue-black granules after appropriate 
staining, was described first at the end of the last century by Grawitz96a, and the 
use of this aid in the diagnosis of plumbism spread rapidly. Under the name of 
basophilic stippling it has been the subject of numberless studies, the results of 
which may be briefly summarized. Basophilic stippled cells are youthful red 
corpuscles, reticulocytes, (Aub and Associates5) which have been altered by the 
presence of lead in the blood. Lead stimulates the bone marrow to increased 
production of red blood cells and also increases their destruction (Seiffert and 
Arnold284a). The stippled cells are not peculiar to lead intoxication but occur 
under many other conditions such as exposure to aniline, carbon monoxide, 
benzol, even various inert dusts (Lehmann183a) as well as in other diseases where 
there is blood cell destruction and regeneration. These cells may be found also 
in normal persons not exposed to lead. Sanders2703, found in a study of 2,231 men 
employed in oil refining with no lead exposure as many as 32.5 per cent, with 
stippled cells. 
On the other hand a case of undoubted plumbism may fail to show this sign. 
Teleky311a says it fails just when most needed, in the slow chronic form of poison- 
ing; it is definitely present chiefly in the rapidly developing acute cases. Kehoe 
did not find it in acute poisoning from tetraethyl lead. Yet this change in the 
red blood cells is of decided value in making a diagnosis of lead absorption, if 
used with proper reservations; some would say, of intoxication, since there is 
evidently an effect on bone marrow and circulating blood. In the first place 
their number in leaded blood is way out of proportion to the degree of anemia. In 
the second place their presence in large numbers is undeniably significant, al- 
though there is wide disagreement as to how large the number must be. It runs 
from about 500 per million reds (Badham and Taylor9b) to over 9,000 per million 
(Sanders270a). 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Since stippled cells are damaged young red cells, Jones reasons that a count 
of reticulocytes will yield earlier results. Mayers204a makes the same claim for 
polychromatophilia, while McCord and his colleagues209*1 look for a clumping of 
the reticulum in immature cells, basophilic aggregation, an earlier and more 
dependable sign than stippling. 
The changes in the white blood cells are insignificant. A relative lympho- 
cytosis has been described, but it is seen in too many other conditions to be an 
aid in diagnosis. The degree of anemia is seldom high, even in severe cases, 
though the author has seen counts as low as 3,100,000 red blood cells. 
Absorption of lead is best proved by demonstrating the presence of lead in 
blood serum and urine in quantities greater than occur in persons not exposed to 
lead. Detection of lead in the feces is less important, for though it proves lead 
exposure, it does not prove absorption. Even in blood and urine the lead to be 
significant must reach a variously determined figure. Fretwurst and Hertz83b 
first announced in 1930 that finding lead in the excreta was not conclusive of 
plumbism, since they had found in persons not exposed to lead as much as 0.01 to 
0.07 mgm. per liter in the urine and up to 0.14 mgm. per liter in the feces. These 
findings since then have been confirmed repeatedly, and there is now a fair con- 
sensus as to the quantity which can be regarded as significant. The New York 
Industrial Hygiene Division in the State Department of Labor accepts this 
standard: lead in the urine above 0.1 mgm. per liter, in whole blood above 
0.1 mgm. per liter, in feces above 0.08 mgm. per gram of ash. 
Webster325a of the Public Health Service found in adults with no known ex- 
posure to lead an average of 0.03 mgm. per 100 c.c. in the urine. Kehoe and 
Thamann160a, who have made extensive studies in this field, accept as the mean 
lead content for normal persons with no industrial exposure, 0.03 mgm. per 
100 c.c. of blood, 0.02 mgm. per liter of urine. In actual lead poisoning one should 
expect an average rate above 0.21 mgm. per liter of urine39b. 
The presence of hematoporphyrin in the urine has been taken as proof of 
lead absorption (von Embden and Kleerekoper), but others find it less trust- 
worthy a proof than stippled cells (Aub5). Schmidt-Kehl275c in a self-experiment 
found that ingestion of white lead caused an increase in urobilin in the stools which 
ran parallel to the fall in the red cell count. 
The lead line is an excellent sign of lead absorption, but* unfortunately it is 
not often found except in workers with heavy exposure and never in the healthy 
or the toothless mouth. It must be remembered also that bismuth poisoning 
produces a similar appearance and so does mercury. Thus Wright349 found a 
blue line on the gums of 3 out of 100 hatters exposed to mercury; Glibert90a 
of Belgium found it in 57 or 12.8 per cent, of 463 hatters-furriers. 
The line is a bluish black stippling, which appears along the margin of the 
gums, usually showing most clearly along the lower incisors but often also on 
Vol. IV. 445 LEAD 
the lining of the cheeks. It cannot be rubbed off but lies within the tissues. It 
consists of the black sulphide of lead produced by contact of the absorbed lead 
with the hydrogen sulphide which is formed by the decay of protein matter 
between the teeth. For this reason it is not found in men who take scrupulous 
care of their teeth, and Aub observes that rabbits living on vegetables, even when 
severely poisoned, never have this lead line, while cats eating meat almost in- 
variably show it quite clearly. 
For the diagnosis of lead intoxication the former tests furnish the ground work. 
In addition there must be a picture of clinical intoxication based on subjective and 
objective symptoms. Among the first are increasing fatigue, loss of appetite, 
especially in the morning, a disagreeable taste in the mouth, indigestion with 
eructation of gas, increasingly obstinate constipation, headache, disturbed sleep, 
pains in the joints. Among the signs, which may be looked for, pallor is the most 
common, a greyish or livid color, familiar to lead workers and out of proportion 
to the degree of anemia. Tremor seen first in the middle and ring fingers, when 
they are held in extension, is considered an important sign, and even more im- 
portant is the detection of extensive weakness in the hand which is used most in 
work. There may be atrophy of the palsied muscles, but sometimes it is hidden 
by edema in the tendon sheath. Josephson157b found marked tenderness along 
the ulnar nerves especially in the right arm. Lewey and Weiss188b urge the use 
of a very sensitive test, chronaxia, for the larval stage of lead poisoning. This 
consists in determining the minimal length of time the galvanic current of 
standard strength requires to flow so as to induce a muscular contraction. A 
reaction below normal, a hypoexcitability, according to them is proof of plumbism. 
In a study of 381 lead workers made by the New York State Department of 
Labor Mayers204a found 232 with evidence of lead absorption, and of these 222 were 
active cases of plumbism. Gastrointestinal symptoms were found in 192 with 
laboratory evidence of lead absorption in 136, disturbances referable to the nerv- 
ous system in 143 and referable to the muscles and joints in 42 cases. 
The picture of tetraethyl poisoning differs from that caused by non-volatile 
lead compounds. It is more rapidly absorbed than any other compound of lead 
in industrial use. In severe cases, such as those which occurred in 1923, there is 
a profound effect on the central nervous system, the symptoms of which are 
insomnia, delusions, excitement, muscular twitching and jerking, hallucinations 
like those of delirium tremens, maniacal attacks. Very characteristic in severe 
cases is a marked fall in blood pressure and body temperature and a low pulse 
rate. In two cases the temperature rose just before death to 1 io° F.65a. Autopsies 
on four fatal cases were made by Norris and Gettler238a, who isolated a volatile 
lead compound from the brains of two men in whom death had occurred within 
24 hours after the appearance of severe symptoms. 
Milder forms were reported by Kehoe and associates16015 and by Machle194a. 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
The latter followed for some years 78 cases, which showed such symptoms as 
early fatigue, sense of weakness, insomnia, disturbing dreams, headache, mental 
excitement, dizziness, tremors as well as gastrointestinal symptoms. 
There is still controversy over some of the lesions attributed to the action of 
lead, such as various types of kidney disease, general arteriosclerosis with con- 
tracted kidney or with gangrene of the extremities, hypertension, peptic ulcer, 
multiple sclerosis. 
Animal experiments with compounds of lead usually show that the kidneys 
are the only organs to suffer much damage (Fairhall and Miller71b, Calvery30b). 
Volhard and Suter320a say lead is a vascular poison, and its effect on the kidneys 
is due to a disturbance of renal circulation, a throttling of renal vessels causing 
anoxemia and degeneration of the epithelium with a gradual thickening of the 
vessel wall and narrowing of the lumen. Ophiils245a produced in guinea pigs 
severe degenerative changes in the kidneys accompanied by regenerative activity 
and fibrous thickening of the capsules, enough in some to give a somewhat gran- 
ular appearance. Vigdortschik319c of Leningrad, on the basis of a study of 2,769 
men, 1,437 in lead work and 1,332 in non-lead work, found a sclerotic kidney 
three times as often in the first group as in the second. Baader9 recently reported 
that he had seen 3 cases of contracted kidney, which were indubitably con- 
nected with plumbism. The kidney is anatomically the same as that of the later 
stages of glomerular nephritis, is slow in developing, 20-30 years, and is caused 
by repeated spasmodic contraction of the kidney vessels causing arteriosclerosis. 
Staehelin300b also finds symptoms of contracted kidney in the later stages of the 
majority of cases of chronic plumbism, while in acute cases albuminuria and 
casts accompany the colic. Vallery-Radot319a saw a case of severe acute plumbism 
with oliguria, albumin and casts and high blood pressure which developed 
later into one of chronic nephritis. 
Perhaps the most striking evidence of a chronic glomerular nephritis following 
long after an acute attack of plumbism is to be found in the reports from Queens- 
land, Australia. Early in the century Gibson88a had reported many cases of 
plumbicuocular neuritis among the children in this Australian state, 428 in a 
period in which only 1 and 4 occurred in other states. Gibson traced the poison- 
ing to the white lead paint on the verandas where the children play, paint which 
under the very hot sun cracks and powders. The same conditions do not exist in 
the other Australian states. Some years later it was found that deaths from 
chronic nephritis in people between 10 and 40 years of age of both sexes were 
strikingly more frequent in Queensland hospitals than in those of other states, 
1,070 per 800,000 population against 449, 368 and 344 in three other states 
(Nye238b). 
Not only glomerular nephritis but general arteriosclerosis and hypertonia, 
which may or may not be accompanied by the former two, have been attributed 
Vol. IV. 445 LEAD 
to the action of lead especially by the older authorities (reference no. 119 p. 32). 
Here there is decided difference of opinion. Animal experiments seem to deny 
that such an effect is produced by lead (Fouts and Page80c), but it is never pos- 
sible to reproduce in animals the slow, long-drawn out exposure to minimal doses 
which occurs in industrial life. 
Two large-scale studies have been made on groups of workmen with regard to 
high blood pressure. Thus Mayers204a in an examination of 381 lead workers 
found hypertension in 98, 66 of them without an associated arteriosclerosis. She 
believes that the action of lead on the neurovascular system, causing constriction 
of the vessels, may be responsible for this hypertension. However, as concerns 
the incidence of general arteriosclerosis there was no significant difference be- 
tween the two groups of workmen; the rate was high for non-lead as well as for 
lead workers. 
Vigdortschik3190 studied 2,769 hospital records of workers, 1,437 in lead, 1,332 
in other work. He found systolic hypertonia in 15.7 per cent, of the former and 
7.4 per cent, of the latter. Excluding cases of essential hypertonia the difference 
between the two groups rises to 34.6 per cent, in the 30-39 year group. There were 
225 cases of hypertonia associated with kidney changes in the lead group, 99 in 
the control group. Marked nephrosclerosis was found in 4.1 per cent, of the lead 
workers, other kidney changes in 8.4 per cent.; the figures for the controls were 
1.4 and 3.9 per cent. 
A fatal apoplexy in a man with arteriosclerosis and chronic plumbism was 
described by Ruhl268b. There were several cerebral hemorrhages and the blood 
pressure increased markedly, with increase of cerebral symptoms. At autopsy 
there were marked arteriosclerosis and contracted kidneys. The man had been 
a painter for 37 years. On the other hand Aub5 is sceptical as to the connection 
between plumbism and hypertension or arteriosclerosis, and Belknap12e believes 
there is no connection. 
Baader9 quotes French and German authors on the subject of spontaneous 
gangrene in lead poisoning and reports a case that he saw with gangrene of the 
big toe in a painter. The prognosis is good in such cases. 
Another controversial subject is the relation of lead poisoning, especially the 
gastrointestinal form, to peptic ulcer. Schiff275b of Vienna discussed the question 
on the basis of some 48 cases of gastrointestinal plumbism. He finds the cause to 
be a condition of intense spastic irritation of the whole visceral nervous system, 
a condition which is not limited to the period of typical colic but is long-continued 
as evidenced by the obstinate constipation and by the whole gamut of sensory, 
motor and secretory disturbances, gastralgia, vomiting, hyperacidity, hyperse- 
cretion and in rare cases, cardiospasm. The colic itself is simply a paroxysmal 
discharge of this state of irritation. Lead resembles in its action pilocarpin as 
shown in Westphal’s experiments, when by injection of this substance he produced 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
vagus irritation with spastic ischemia of the intestinal tract and resulting ne- 
croses. Indeed lead prepares the ground for neurogenic ulcers as does no other 
agent. The action is central, but it is aided by a peripheral neuritis of the vagus. 
Schiff holds that typical colic with its single attacks of intense pain is not 
nearly so common as are symptoms of prolonged or chronic disturbance, recurrent 
attacks of pain lasting for months perhaps, sometimes coming on daily at the 
same hour, remitting for a while, then recurring in the same way. Often the pain 
is related to certain foods as in gastric ulcer or to fasting as in duodenal ulcer. 
Especially common is pain at night followed by acid vomiting in the morning. 
Of the 48 cases which he studied 14 proved to have indubitable ulcer, 10 had 
symptoms typical of duodenal ulcer, 1 had cardiospasm, 16 had severe gastralgia 
with high grade hyperacidity and hypersecretion and 7 had symptons suggestive 
of ulcer but without secretory irritation. 
Cushing’s theory (personal communication) was that lead causes inflammation 
of the parasympathetic nervous system which controls gastric secretion and 
motility. 
Teleky in 1929 reported a case of gastric ulcer in a zinc smelter, who had a 
history of frequent attacks of colic; also a case in which a severe colic apparently 
was the cause of the lighting up of an old gastric ulcer. Adler of Vienna reported 
that same year 4 cases of plumbism complicated with duodenal ulcer and a fatal 
case of colic with bloody vomit in a man who had had many attacks of lead colic. 
The autopsy in this case showed a ruptured gastric ulcer, and the rupture was 
attributed to the spasmodic contractions of the stomach under the action of the 
lead. Glaser89b, Gutzeit108a and Koelsch166a all hold that peptic ulcer may be 
caused by lead. 
However Czepai47a, chief diagnostician of the Hungarian Social Insurance 
Institute, was unable to find any connection between plumbism and gastric ulcer. 
The frequency of gastric ulcer among 8,975 workers was 17.9 per cent., among 
450 lead workers it was only 8.8 per cent. He believgs that the statements quoted 
above were based on too small a number of observations. 
Finally there are those who hold lead responsible for multiple sclerosis. Cone, 
Russel and Harwood43a suggest it as a possible causative factor in the remitting 
and exacerbating type of this disorder. In 6 cases of this type they found lead in 
stools, urine and cerebrospinal fluid. There was lead in the spinal cord at au- 
topsy in a typical case of multiple sclerosis, and in the brain and cord of a case 
of neuromyelitis optica. Calcium therapy was found to be of distinct value. 
Bosches17b the following year discussed this theory and dismissed it, holding that 
there is no adequate proof for it and ample evidence against it. 
Two recently published studies of lead deserve mention. Byers and Lord30a 
present evidence showing that lead poisoning in childhood has a decided effect on 
mental development. They made a follow-up study of 20 school children, who 
Vol. IV. 445 LEAD 
had been in hospital for lead poisoning in infancy or early childhood. There was 
no marked encephalopathy, and all were discharged as recovered. The school 
records showed that only one had made satisfactory progress in school; the others 
had behavior difficulties, loss of normal inhibitions, were unreliable, cruel, im- 
pulsive. Three had recurrent convulsions, one had a positive Babinski reaction, 
another, hyperactive reflexes and sustained ankle clonus after 6 years. 
Riggs and his colleagues2643 found a significantly higher concentration of lead 
in the kidney and the pituitary gland in autopsies on 95 patients whose death was 
not adequately explained by clinical or necropsy findings as compared with 40 au- 
topsies on patients with clearly defined causes of death. In the first group of 
these patients neuropathy as the chief cause qf illness, repeated vomiting, pe- 
ripheral collapse and elevated blood pressure without organic substrata occurred 
with significantly greater frequency than in the second group. 
Vol. IV. 445 MERCURY 
611 
Mercury 
Industrial poisoning from mercury and its compounds differs from acciden- 
tal or suicidal poisoning by bichloride of mercury or the poisoning that follows 
mercurial inunctions. One does not look for severe abdominal symptoms and 
nephritis but for three characteristic symptoms, inflammation of the gums with 
salivation, muscular tremors and a form of nervous shyness which Kussmaul175 
called erethism. Usually the first thing noted is pain when chewing and excessive 
flow of saliva. The gums swell, bleed readily; the teeth loosen and may drop 
out. In severe cases there is not only pyorrhea but ulcers in the mouth and on 
the lips. In slow chronic poisoning there may be no salivation and no marked 
inflammation, only a complaint of dryness of the mouth and throat. 
in the fairly rapidly developing cases stomatitis may be the only symptom 
noted, but usually muscular tremors also are present. These affect at first only 
the small muscles, those of face, tongue and fingers, and are seen easily, when 
the tongue is protruded, and when the hand is stretched out with the fingers 
separated and extended. It is an intention tremor increasing with the effort to 
control it, and it often happens that a man with this form of poisoning may be 
able to keep on with the accustomed movements required by his daily work, 
when it is almost impossible for him to perform a more unusual action, such as 
raising a glass of water to his lips. The tremors may affect other muscles, and 
in more advanced cases there are also violent jerking movements making work 
impossible and making the victim as helpless as a baby. Yet even in these severe 
cases the movements may die down altogether, if the man is quiet and feels him- 
self free from observation. This does not mean that the palsy is hysterical in 
character; it is a part of the peculiar psychosis of mercurialism. Kussmaul’s 
erethism is a form of nervous shyness and shrinking with loss of confidence, 
vague fears, inability to perform even the simplest act under observation. Some- 
times there is great irritability with outbursts of anger on trivial provocation, in 
other cases drowsiness and apathy. Poor sleep also is common with despondency 
and loss of memory in the severer cases. L. I. Harris127 in his investigation of 
New York hatters found that some of them would throw down their tools when 
he paused beside them and declare that they could not work if anybody watched 
them. Teleky312 gives some striking cases of this kind of psychosis. Fellinger and 
Schweitzer73 claim that endarteritis followed by gangrene of the toes or feet was 
a sequel of mercury poisoning in three workmen (see Part II). 
In the United States the most serious cases of industrial mercurialism occur 
in the metallurgy of cinnabar, mercury sulphide, which is itself harmless48, in 
making thermometers and like instruments, in laboratory work-87, in the use of 
mercury solder, repair jobs with the acetylene torch, in short any job which re- 
Vol. IV. 944 612 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
quires the application of heat (Williams and Schram336). A new source of mer- 
cury poisoning is its use in antifouling paint02. 
A much slower form is seen in the felt hat industry, where for centuries mer- 
curialism has been notorious, as witness the expression in England, u as mad as a 
hatter ”, in the United States, “ Danbury shakes ”. As a usual thing the felt 
hat industry does not give rise to serious forms of mercurialism, for the exposure 
to mercury is not great in most plants. This industry is responsible for much 
the largest number of cases in all industrial countries, but the form usually is slow 
and mild. Mercuric nitrate is used in the process known as “ carrotting ” the fur 
of rabbits, beavers and muskrats in order to make the scales of the hair separate 
from the cylinder and to soften and twist the cylinder, thus increasing the capacity 
of the fur to felt, that is, to form a closely tangled mat. Most of the mercury is 
given off from the carrotted fur during the various processes the felt undergoes. 
Several examinations of groups of workers in the hatter’s trade have been 
made in the United States. L. I. Harris127 in 1912 found 40 incontestable and 
20 probable cases of mercurialism among 212 hatters’ furriers in New York. In 
1922 Wade Wright349 examined 168 hatters and hatters’ furriers in Danbury, 
Connecticut, and found that 53 showed at least two of the three classic symptoms. 
Two studies were made by the United States Public Health Service and published 
in 1937 and 1941233’234, the first covering fur cutters, the second felt hatters. 
Fifty-nine cases of chronic mercurialism were found among 534 hatters. They 
had worked in air containing from 2.1 to 5.0 mgm. of mercury per 10 cubic meters 
of air, and the incidence of mercurialism was seen to increase with the increasing 
amount and duration of exposure, if the latter ran above 1.0 mgm. per cubic 
meter of air. As a result of this investigation it was possible for the Federal and 
the Connecticut health authorities to bring about a voluntary abandonment of 
mercurial carrot on the part of the felt hat manufacturers, thus making safe what 
has been for centuries a dangerous trade. At a conference, called by the Public 
Health Service in Washington on May 19, 1941, of manufacturers’ and labor 
organizations, a resolution to become effective December 1st, 1941 was passed 
unanimously. It prohibited the use of mercurial carrot in the preparation of 
hatters’ fur or the use of such fur in the manufacture of hats. 
Organic compounds of mercury have been used extensively in England since 
1914 as fungicides, most often the dimethyl compound. Hunter and his col- 
leagues140 describe four cases which originated in a factory producing fungicides. 
The symptoms were not those of poisoning by inorganic mercury except the 
tremor, for the nervous system alone was affected. There was ataxia, dysarthria 
and gross constriction of the visual fields but no changes in memory or intelli- 
gence. In rats the peripheral nerves and posterior spinal roots were affected first, 
later the middle lobe of the cerebellum. 
Vol. IV. 944 MANGANESE 
613 
Atkinson4 has adanced a new test for the diagnosis of mercurialism, namely 
a brownish colored reflex from the anterior capsule of the lens. He found it in 
37 of 71 men who had been exposed to mercury. Of these, 14 showed symptoms 
of mercurialism, and in all the colored reflex was present. 
Mercury fulminate is a skin irritant, but systemic poisoning from absorption 
is very rare, though occasionally there may be a mercurial salivation. Some very 
unusual cases were reported recently from France, cases of acute edema of the 
face with spasmodic coryza, anaphylactic in character, in four newly employed 
men. There was also a fall in blood pressure, leucopenia and albuminuria. There 
were also two cases of “ gassing ” with loss of consciousness, probably from ethyl 
nitrite which is given off in the production of fulminate. 
For metallic mercury the maximum allowable concentration should be 1 mgm. 
per 10 cu. meter according to the American Standards Association. 
Manganese 
The literature on this rare and clearly characterized form of industrial poi- 
soning was reviewed by Edsall and Drinker in 1919, when 15 cases had been de- 
scribed in Germany and France among workers exposed to dust containing man- 
ganese as oxides and silicates and 9 (Casamajor36) in the United States. The 
cases seen by Edsall, Wilbur and Drinker64 brought the number in America up 
to 39. Two more were reported by Davis and Huey60 in 1924 and 6 by Gayle86 
in 1925. Since then reports from Europe and America have swelled the number, 
and by 1937 McNally-13 had collected 131 cases from the literature. 
Edsall and Drinker give the following list of symptoms, in the order of their 
appearance: a history of work in manganese dust for at least three months; 
languor and sleepiness; muscular twitchings from fine tremors to gross rhythmi- 
cal movements of limbs, trunk and head; cramps and stiffness in the calves, 
especially at night; slight increase in tendon reflexes; ankle and patellar clonus; 
retropulsion and propulsion; peculiar slapping gait; occasionally uncontrollable 
laughter; less often weeping; absence of sensory, gastrointestinal, eye and genito- 
urinary disturbances; negative blood, urine and spinal fluid findings. The prog- 
nosis is hopeless as to recovery but favorable as to life. 
The diagnosis of manganese poisoning is not easy; indeed in the absence of 
a history of exposure probably it would prove impossible. Isolated cases prob- 
ably escape detection as industrial in origin. Gurtner says that the symptoms 
may simulate progressive bulbar paralysis, amyotrophic lateral sclerosis, post- 
encephalitic Parkinsonism, multiple sclerosis, progressive lenticular degeneration 
(Wilson’s disease), and only a history of exposure will clear up the puzzle. 
Flinn, Neal and Fulton79 investigated an outbreak in a Pennsylvania ore- 
Vol. IV. 944 614 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
crushing plant. They estimated the particles of dust in the air and made ex- 
haustive examinations of 34 men exposed to ore dust. Eleven were found to 
have manganese poisoning, 8 of them incapacitated at the time. The picture 
given corresponds to that described by Edsall and Drinker, but in addition a 
leucopenia was noted especially in the advanced cases. 
The average exposure to manganese in the air was 40 mgm. per cubic meter, 
the highest was 173 mgm. The lowest average concentration at which chronic 
poisoning was found to have occurred was 30 mgm. per cubic meter. 
Several experimenters have succeeded in producing symptoms and lesions 
resembling those of manganese poisoning in man217. Canavan, Cobb and 
Drinker32 made a very complete study of the pathological changes in the body 
of an old manganese worker, who died of cardiorenal disease at the age of 69 
after about 14 years of disability from manganese poisoning. There was atrophy 
of the brain, which showed most strikingly on frontal section, for the lateral 
ventricles were dilated and the basal ganglia so shrunken as to distort the anatomi- 
cal outlines. It was in these ganglia that the significant pathological process was 
found, degeneration of nerve cells with gliosis, which affected the caudate nu- 
cleus, the putamen, the globus pallidus and the thalamus, the last most severely. 
A curious autopsy report comes from Germany. Voss321 describes the find- 
ings in the body of a man with manganese poisoning who died of bronchopneu- 
monia. He found no changes in the basal ganglia, only in the right pyramidal 
tract and in the fibres of both sciatic nerves. The principal use of manganese is 
in the iron, steel and alloy industries. A much less important use is in the mak- 
ing of dry cell batteries. The ore comes chiefly from Russia, India, Brazil, but 
there are deposits in the United States and the wartime demand is leading to their 
exploitation. The breathing of dust-laden air in mines and mills is the way in 
which industrial poisoning occurs, and usually it is a slowly cumulative action, 
taking a year or more to develop, but cases have been known to follow as little as 
three months’ exposure. Lately a new source of manganese poisoning has come 
to light, namely the fumes from welding manganese alloys. 
The American Standards Association has adopted 60 mgm. per 10 cu. meter 
of air as the maximum allowable concentration of manganese. 
Metal Fume Fever 
Brass founders’ ague, spelter shakes, brass chills, one of the oldest forms of 
industrial disease in the brass and zinc industries, now is included under the 
term “ metal fume fever ”, together with a similar symptom complex, which 
follows exposure to superheated copper124, to magnesium oxide16 and to other 
metals. Brass is an alloy of copper and zinc, and there was for many years a 
Vol. IV. 944 CADMIUM 
615 
controversy as to which element was responsible for the ague-like attack so 
familiar to brass founders. Although as early as 1831 Thakrah attributed the 
illness to the oxide of freshly burned zinc, Lehmann in 1910185 settled the ques- 
tion definitely by producing in himself and four others typical brass chills from 
breathing the fumes of burning zinc, and he isolated zinc from the urine. These 
results have been confirmed repeatedly. Guelman108 found glycosuria caused by 
disturbed glycogen metabolism in 8 out of 28 cases of brass founders’ ague, and 
in 13 of the 15 men examined for blood sugar he found an increase. 
Zinc oxide is not toxic, but neither is the illness produced by brass fumes 
typical of a metallic intoxication; it resembles, as Lehmann pointed out, an acute 
infection, and it is followed by a certain degree of immunity. Lehmann’s ex- 
planation of the pathology still is the accepted one. The particles of oxide are 
inhaled, they spread over the surface of the alveoli of the lungs, where they exert 
a destructive action on the epithelial cells, and it is the absorption of proteids 
from these dead cells that produces the malaise, chill, fever, leucocytosis, etc. 
The reason why the illness cannot be brought on by breathing ordinary zinc 
oxide powder, according to Philip Drinker56, is that the latter consists of large 
agglomerations of oxide particles, while the freshly sublimed particles are small 
and very dry, passing easily through the bronchioles. 
The same clinical picture was produced by Drinker and his associates56 with 
freshly sublimed magnesium oxide. Koelsch166 saw typical ague in men rolling 
red-hot copper ingots and Hanson124 in men melting copper in an electric fur- 
nace. The reason why brass workers suffer most is that zinc melts at a much 
lower temperature than does copper, and therefore, in making the alloy zinc 
fumes are produced in abundance long before the copper is melted. Other in- 
dustries, which give rise to zinc oxide chills, are bronzing, zinc smelting, zinc 
coating (galvanizing), autogenous welding of zinc or galvanized iron and work- 
ing up dross from galvanizing tubs. 
It is a question whether there is a chronic form of metal fume fever, but there 
can be no question of an accumulation of effects, if the attacks are very frequent. 
Brass founding is not a healthful occupation (Guelman108), but in all cases of 
chronic illness in these men it is well to look for lead. Both brass and so-called 
railway bronze may contain as much as 9 per cent, of lead which volatilizes with 
the zinc and causes typical plumbism (Pedley and Ward249). 
Cadmium 
Cadmium, which was for long a rare metal in industry, of late has become 
very important as an ingredient of alloys and in electroplating. Exposure, there- 
fore, comes in the smelting of ore148, making alloys, electroplating, making and 
Vol. IV. 944 616 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
spraying pigments and in welding metal when the metal or the welding rod con- 
tains cadmium. 
Industrial poisoning from cadmium was a medical curiosity as late as 1932, 
when Prodan262 published his valuable experimental studies. It is still a rare 
finding, but that may be because cases have gone unrecognized, and since the 
use of the metal is increasing rapidly, physicians doubtless will become more 
familiar with the picture of its physiological action. Striking cases in the ear- 
lier literature were decribed by Sovet (Prodan), by Legge181 and Schwarz281. 
Sovet’s 3 cases were acute, with gastrointestinal disturbances, profound prostra- 
tion and oliguria with tenesmus. The others, chronic, had involvement of the 
lungs, dark urine and gastrointestinal inflammation. 
The recent literature yields several illustrative cases. Nasatir232 of the Na- 
tional Institute of Health reports a fatal case. Death occurred on the fifth day 
after exposure to cadmium fumes caused by burning off with an oxyacetvlene 
flame deposits of metal containing a high percentage of cadmium. The clinical 
symptoms consisted of an increasing feeling of constriction of the chest and in- 
creasing dyspnea and cough which became extreme before death. 
A brief report of one industrial case and mention of a second comes from the 
Ohio Industrial Hygiene Bulletin, 1939. The poisoning resulted from accidental 
overheating of cadmium. The victim suffered from weakness, dyspnea, pain in 
the chest, paroxysms of coughing and profuse sweating. There were moderate 
fever and moist rales over the lungs, no other symptoms. 
Bulmer, Rothwell and Frankish26 reported in 1938 15 cases with 2 deaths. 
Postmortem examination revealed congestion of the lungs with edema, hemor- 
rhage and partial collapse. The cells of liver and kidneys showed cloudy swelling. 
It is evident that in man as in Prodan’s experimental animals the action of 
cadmium fumes and dust is chiefly on the lungs; other effects are far less im- 
portant. The symptoms resemble those of nitrous fume poisoning. A case seen 
by one of us (R.T.J.) was very characteristic. This was in a young Mexican 
laborer, who was sent to the hospital as a case of metal fume fever following the 
use of an acetylene torch on the inside walls of a furnace in which cadmium 
residues had been recovered from scrap metal. He was extremely ill with severe 
dyspnea and exhaustion, and he gave a history of severe headache, constant 
coughing and chest pain, which came on soon after his job was over. His lungs 
were clear, but his respirations were 40, pulse 130, temperature ioo° F. Oxygen 
administration failed to affect his respiratory rate but lessened the chest pain. 
The temperature rose to 104° F., pulse to 140 and respiration to 50, and the 
leucocyte count was 21,100 with 87 per cent, polynuclears. A patchy broncho- 
pneumonia was revealed by x-ray. Nine days after exposure the pulse rate was 
160 and respiration 70 and cyanosis was marked. Just before death a wide- 
Vol. IV. 944 BERYLLIUM 
617 
spread patchy pneumonia was evident. Blood and urine were essentially normal; 
Wassermann was negative. At autopsy the lungs were edematous and contained 
solid areas from which seropurulent fluid could be expressed. The cause of death 
was bronchopneumonia with edema. No significant change was found in any 
other organ. 
The Indiana Bureau of Industrial Hygiene reported in 1943 2 cases of severe, 
acute, cadmium poisoning caused by the fumes from the use of a blow torch on 
cadmium-plated steel pipe. After four hours of this work both men were vio- 
lently ill with vomiting, pains in the chest and difficult breathing. One recov- 
ered ; the other died four days later “ of a severe chest involvement ”. 
Cadmium poisoning has been reported also from eating acid-containing foods 
such as fruit juices left standing in cadmium plated cooking utensils or “ ice- 
cube ” trays. 
The American Standards Association has adopted as the maximum allowable 
concentration of cadmium in the air, 1 mgm. per 10 cu. meters. 
Beryllium 
Up to 1938 the articles on beryllium or sometimes, glucinum poisoning as 
an occupational disease came almost entirely from Russia. Guelman summa- 
rized them that year for the I.L.O. Encyclopedia. Beryllium is a rare metal ex- 
tracted from beryl, which is 14 per cent, beryllium oxide and is present in many 
silicates and phosphates. It is a very valuable addition to alloys, making them 
more resistant and harder, and its use has increased greatly during the present war. 
Dust in very fine division is the hazard in most processes, but in those that re- 
quire great heat the metal itself is liberated. Hydrogen fluoride comes off much 
earlier, however. 
The Russian publications show that it is not easy to separate the action of 
beryllium and its fluoride compounds from that of other fluorides. They ob- 
serve an irritant action on skin, mucous membranes and conjunctiva, rarely seri- 
ous in character. They also observe, in the extraction of beryllium by heat, 
symptoms of metal fume fever, but this is followed often in a few days by a 
pulmonary disorder, cough, reduction of chest expansion, numerous moist rales 
and an x-ray picture resembling miliary tuberculosis. Toward convalescence 
bronchioalveolitis appears and occasionally more or less pronounced pneumo- 
sclerotic changes. 
Guelman tested the oxide and the oxyfluoride on animals and found the 
former to give rise to only slight damage, while the oxyfluoride set up a fatal, 
necrotic, fibrinous pneumonia. He concludes that the principal role in this form 
of occupational poisoning is played by beryllium, aggravated by fluorine. 
Vol. IV. 944 618 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Fairhall and his colleagues71 as a result of exhaustive studies of the action 
of beryllium and its compounds, when administered to animals, conclude that 
beryllium is not of itself toxic, but that the fumes arising from the electrolysis 
of molten fluorides containing beryllium fluoride or oxyfluoride are decidedly 
toxic. Such salts of beryllium as the fluoride and sulphate, which hydrolyze 
easily, were found to have an irritant effect on the skin, but not the neutral salts. 
A comparison of the relative toxicities of beryllium, magnesium and zinc by in- 
traperitoneal injection showed the first to be least, the last most toxic. 
Since no consistent pathological change can be attributed to beryllium, “ it 
appears that whatever toxicity has been found to occur with the beryllium salts 
is due to the toxicity of the acid radical such as the fluoride or oxyfluoride or to 
an objectionable condition brought about by the hydrolysis of certain of its salts, 
such as the chloride and sulphate. No safe permissible working standards should 
be based upon beryllium alone.71 ” 
More information on this subject may be looked for soon, since studies are 
being carried on by several industrial companies as well as by the National In- 
stitute of Health. 
Magnesium 
Mention has already been made of the fact, confirmed by P. Drinker’s ex- 
periments on man, that magnesium oxide56, freshly formed, can set up metal 
fume fever. A much more serious injury from magnesium has come to light re- 
cently, chemical gas gangrene from metallic magnesium. This is a new form of 
industrial injury, which the extensive use of metallic magnesium has brought 
about. According to McCord and his colleagues210 wounds, scratches or cuts, 
that are caused or contaminated by magnesium or its alloys, are especially prone 
to become severely inflamed with accompanying blebs, and these lesions are ob- 
stinate, lasting for months. They succeeded in producing in animals sizable 
gaseous tumors by injecting under the skin particles of magnesium or an alloy, 
but not with aluminum or manganese. Analysis of the gas showed H2 2.2 per 
cent., C02 1.3 per cent., 02 15.2 per cent., and the remaining 81.3 per cent, prob- 
ably is No. The Bulletin of the British-Colonial Board of Health, 12.33.1942, 
calls this “ a new kind of gas gangrene ” and urges that all particles of magne- 
sium be removed promptly from the wound. 
Jarzynka154, who has had a five year experience with magnesium metal in 
fabrication, has seen 73 major burns and insists that they differ in no respect 
from the usual second and third degree burns. 
In magnesium foundries fumes of S02 and of fluorides may be present espe- 
cially in pouring. 
Vol. IV. 944 ZINC 
619 
Vanadium 
in 1911 Dutton62 described vanadium poisoning as he had seen it in a plant 
where vanadium ore was ground and prepared for use in steel production. His 
patients suffered from anemia with evidences of destruction of red blood cells 
preceded by polycythemia and a high hemoglobin. Loss of appetite, pallor, ema- 
ciation followed; there were albumen, casts and blood in the urine; diarrhea or 
constipation, cough, sometimes severe enough to cause hemorrhage, increased 
susceptibility to pulmonary tuberculosis, nervous disorders, hysteria, melancholia, 
dimness of vision occurred. Vanadium was found in urine, feces and saliva. This 
picture of widespread disorders has never been confirmed. 
For many years thereafter little was added to this report of Dutton’s. Then 
in 1939 Symanski306 reviewed the literature, showed that it is only the pentoxide 
of vanadium, particularly in the readily absorbable form of dust, which is harm- 
ful to workers, and gave the results of his examination of 19 men. He observed 
severe, suppurating conjunctivitis, inflammation of the upper air passages with 
continuous coughing and profuse expectoration sometimes with bloody pharyn- 
geal secretion, constriction and pain in the chest; more or less severe bronchitis, 
sonorous and sibilant rales, evidence in x-rays of chronic bronchitis are encoun- 
tered. He saw no evidence of disturbance of the gastrointestinal tract or of the 
kidneys or of the central nervous system; no impairment of vision and no changes 
in the blood picture were seen. 
On the basis of animal studies Malfino196 says that vanadium anhydride is 
absorbed and is eliminated in the urine, where it can be demonstrated; it has a 
strongly irritant action on the respiratory tract. 
Zinc 
The commonest form of sickness caused by a compound of zinc is the so-called 
“ brass founders’ ague ” from inhalation of freshly sublimed zinc oxide. This 
has been discussed under “ metal fume fever ”. Metallic zinc has been regarded 
as giving rise to chronic poisoning with gastric disturbances, even peptic ulcers 
(McCord207), but K. Drinker and her colleagues12 found no acute or chronic 
illness attributable to zinc in 24 workmen, who had been exposed from 2 to 35 
years. However, it must not be forgotten that commercial zinc usually con- 
tains arsenic and that “ zinc white paint ” may really be “ leaded zinc ” with 
5 to 50 per cent, of sublimed white lead. 
In a recent article Gocher91 insists that, if men work in the fumes or dust of 
zinc oxide or chromate or sulphate as well as the chloride, .they develop dermat- 
itis, boils, conjunctivitis, gastrointestinal disturbances and anemia, provided the 
Vol. IV. 944 620 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
exposure has lasted as long as six months. He gives blood counts, which differ 
little from the average for industrial workers, an increase of large mononuclears 
at the expense of the small mononuclears and of the polynuclears, a slight increase 
in eosinophiles. 
Zinc chloride is used as a solder flux and as a preservative of wood. It is 
decidedly caustic. McCord and Kilker207 reported 17 cases of severe skin lesions 
caused by handling wood impregnated with zinc chloride. 
Antimony 
Antimony has extensive use as a constituent of lead-antimonial alloy, espe- 
cially for printers’ type and storage battery grids; it is used also as the “ golden 
sulphide ” in rubber compounding, and exposure takes place in mining and smelt- 
ing. In most of these occupations lead also is present, and the cases of intoxi- 
cation that develop are almost always attributed to the latter, although some 
authorities have described what they consider to be uncomplicated antimony 
poisoning (Seitz285, Schrumpf and Zabel277). Prosser White329 says that occu- 
pational dermatoses from antimony are very rare. Quimby263 has reported skin 
eruptions from antimony pentasulphide in rubber compounders. It is well to 
remember that commercial antimony usually is contaminated with arsenic. 
Contrary to the usual opinion as to the relative harmlessness of antimony in 
industry is the assertion of Bradley and Frederick20, who found in animals a 
damage to the heart muscle developing consistently as a result of administration 
of antimony compounds. They consider this metal more toxic than lead and 
urge electrocardiographic examination of exposed workers to determine the pres- 
ence of damage to the heart. 
Copper 
As the sublimed oxide copper may be responsible for one form of metal fume 
fever. Irritation of the skin may be caused by blue stone, the sulphate, by finely 
divided copper and, according to Prosser White329, by copper chloride, but the 
irritating effect of the dust in copper smelting must be attributed to the presence 
of arsenic (Dunlap61). Mallory198 held the theory that chronic copper poison- 
ing causes cirrhosis of the liver with hemochromatosis. A great majority of the 
cases he described were not connected with industry, but in four the work in- 
volved contact for many years with copper in some form. In these no cirrhosis 
of the liver was found, but moderate amounts of hemosiderin and hemofuscin 
were seen. Mallory’s theory has not been confirmed by later investigation in 
this field. 
Vol. IV. 445 ARSENIC 
621 
Nickel 
Nickel electroplating involves contact with the sulphate and chloride, and in 
susceptible persons these salts produce obstinate eczema. Nickel carbonyl, a 
gas, which is essential to the Mond process of producing pure nickel, has caused 
severe poisoning in England and in Germany. Up to 1934 47 cases with 1 death 
had been reported by the British Factory Inspection Service. It is said to be 
five times as toxic as carbon monoxide, being deposited over the surface of the 
pulmonary epithelium, which suffers severe damage, and passing out unchanged 
to the circulating blood. Fatty degeneration occurs in the vessel walls3,21. 
A strange and hitherto unexplained action of nickel, if indeed it is to be at- 
tributed to nickel, is described in the yearly report of the British Factory Inspec- 
tion Service for 1933. Fourteen cases of industrial cancer had occurred in a 
nickel refinery, of which 13 were fatal. 
Nickel together with cinnamon apparently was the causative agent in a case 
of dry, scaly, hyperkeratotic dermatitis in a baker (R.T.J.). 
Silver 
This is another of many formerly unimportant industrial substances, which 
the exigencies of the present war have brought into more or less prominence. 
Silver can be used as a coating for steel in aviation bearings, in telephone and 
telegraph instruments and bus bars and for lining tanks and pipes in food proc- 
essing. Argyria, a bluish black deposit in the skin of metallic silver, apparently 
is the only lesion produced by silver. It is localized usually in those areas of 
the skin which have come in contact with silver. Generalized argyria follows 
absorption by mouth or by the air passages. Teleky308 has described this form. 
Hill and Pillsbury138 found in the literature 12 cases of localized and 8 of gen- 
eralized argyria, all of industrial origin. The condition appears slowly, taking 
from 2 to 25 years or even longer. There may be pigmentation of the lining of 
the mouth. Argyria, local or generalized from prolonged application or inges- 
tion of silver-containing medicaments, was not very infrequent in the past but 
now has become infrequent. 
Efforts to encourage elimination of the silver have failed, and local treatment 
is of dubious benefit (Heimann132). 
Arsenic 
Arsenic is distributed very widely in nature, being found in almost all sul- 
phide ores, and since the greater part of our lead, iron, copper, antimony and 
Vol. IV. 944 622 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
zinc ores are sulphides, it follows that these metals are very likely to carry ar- 
senic as an impurity. Chamber sulphuric acid, commonly made by roasting iron 
pyrites, frequently is contaminated with arsenic, and the same may be true of 
the hydrochloric acid made from sulphuric acid. The more expensive form of 
sulphuric acid, known as contact acid, does not contain arsenic. 
Arsenical poisoning in industry is caused by exposure to dust of solid com- 
pounds or to the gas, arseniuretted hydrogen or arsine. The latter is much the 
more serious. The solid compounds are white arsenic, As203, the acetoarsenite 
of copper or Paris green, lead arsenate and calcium arsenate. Industrially white 
arsenic is recovered by roasting and subliming arseniferous ores or subliming the 
flue and baghouse dust in smelters which work up such ores. In the lead smelt- 
ers of Utah and Colorado and in the copper smelters of Montana mild arsenical 
poisoning is frequent, but serious cases are very rare. 
Paris green and the two arsenates have a very large use as insecticides, and 
the danger in this use concerns not only the makers of the compounds but the 
sprayers. In England white arsenic is used, together with sulphur and caustic 
soda or potash, for a sheep dip, and similar mixtures are used to preserve hides 
and skins of birds and animals. Arsenical poisoning has occurred in Germany 
among men handling hides from South America, which have been treated with 
arsenic, and there have been cases in England among men unpacking bird skins. 
W. Gilman Thompson316 reported a case of arsenical poisoning with peripheral 
neuritis in a tannery worker and quotes a chemist as having found arsenic in 
11 out of 42 samples of furs. Hayhurst130 found it as an ingredient of glass, one 
Ohio glass factory using as much as two tons of white arsenic in a month. 
The poisoning that results from exposure to arsenic dust usually is local, very 
rarely systemic. Skin lesions of various kinds, dermatitis, eczema, ulcers, sclero- 
derma, bronzing, trophic changes in the nails, loss of hair, inflammation and 
ulceration of the mucous membranes and eyelids, are the commonest results of 
contact with arsenical dusts. Thickening of the skin of the palms may be the 
first symptom noted (Ayres7). Delicate parts of the skin such as the lips or eye- 
lids, where mucous membrane and skin merge, are especially sensitive; so are 
the parts that are kept moist and warm as the scrotum and the axilla. A chronic 
inflammation with slow, painless ulceration of the mucous membrane of the nose, 
which results in perforation of the septum, is according to Dunlap61 of the Ana- 
conda Copper Company a very common accident in arsenic workers. It causes 
little suffering and does not result in deformity, for the bony part of the septum 
and the base are not involved. Dryness of the throat, cough and hoarseness are 
characteristic of arsenic workers. 
In poisoning with lead arsenate the symptoms are more likely to be those of 
lead than those of arsenic. This is a fact well known to men engaged in pro- 
Vol. IV. 944 ARSENIC 
623 
ducing this insecticide, and among the reported cases lead is accused more often 
as the cause than is arsenic. Aub5 saw a case of double wrist drop of 12 years’ 
duration with difficulty in walking for 3 years in a man, who had used lead 
arsenate spray in forestry work for 27 years. On the other hand Kraetzer173 re- 
ported a case of Raynaud’s disease in a patient with typical symptoms of arsenical 
poisoning, contracted by prolonged use of arsenical insecticide in a greenhouse. 
Arsenic was demonstrated in the urine. In one case reported by the British Fac- 
tory Inspection Service for 1933 the lesions pointed to arsenic, not lead; but in 
a second the reverse was true. 
Fairhall and Miller70 studied for 2 years the effect on rats of the arsenates of 
lead and calcium and the carbonate of lead. Most of the kidney damage was 
caused by the lead; blood destruction was greatest with the two arsenates. There 
was less storage of lead in the soft tissues than of arsenic. In the bones there 
was more storage of lead carbonate than lead arsenate, the arsenate radical ap- 
parently decreasing lead absorption or increasing its excretion. 
W. Frohn85 in 1938 published a report of arsenical poisoning in the vineyards 
along the Mosel, where the vines are sprayed, and the vintners also use the skins 
from the winepress to make wine for themselves. The symptoms were lesions of 
the skin and mucous membranes. 
The picture of generalized, arsenical poisoning from solid arsenic, as seen in 
exceptional cases in industry, rarely is severe. Neuralgic pains and multiple 
neuritis with motor palsy, slight in degree, are characteristic of these cases. The 
palsy is likely to affect the long extensors of fingers and toes, as does lead, but 
it is distinguished from the latter by the severe neuralgic pains and by the tend- 
ency toward a multiple, symmetrical neuritis. A very rare form of industrial 
poisoning involving the optic nerve was described by Moleen224, who saw a case 
of skin lesions and double optic atrophy in a man using arsenical insecticides. 
Of 135 cases of poisoning by solid compounds of arsenic, discussed by 
Legge182, 38 had gastric symptoms, 13 had tremors or muscular cramps, 6 had 
peripheral neuritis; of the remainder all had lesions of the skin, in 6 of which 
there were keratoses or epithelioma. He speaks of 3 cases of epileptiform seizures, 
a most unusual manifestation of such poisoning. The carcinogenic action of ar- 
senic has been recognized since the famous pronouncement of Jonathan Hutchin- 
son, and each year one or more cases of arsenical cancer of the skin are reported 
by the British medical inspectors of factories. Usually white arsenic is the agent, 
but recently there was a case of fatal epithelioma beginning in the axilla, which 
was ascribed to exposure to dust of acetoarsenite of copper. 
Arsine or Hydrogen Arsenide. — Much more dangerous is poisoning by the 
gas, arsine or hydrogen arsenide. This is a subtle and powerful poison with a 
rapid characteristic action, but since it is always a result of accidental exposure, 
Vol. IV. 944 624 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
since arsine has no use in industry, and caused by arsenic, which is not known to 
be present, the cases often escape detection. The gas may be given off in any 
process, which requires contact between dilute sulphuric or hydrochloric acid 
and a metal, usually iron, lead, zinc or antimony, and since there is a large num- 
ber of processes in which such contact occurs, there are many possibilities for the 
formation of arsine, for it is only necessary that metal or acid be contaminated 
with arsenic. The essential factors are arsenic and nascent hydrogen, the con- 
ditions necessary for Marsh’s test. Such an accident may occur in so many dif- 
ferent kinds of industries that Wignall330 suggests a search for hydrogen arsenide 
fumes in all cases where a mysterious form of illness shows itself among the 
workers; at least the question should be faced, whether there is any process 
which could possibly result in the production of these fumes. 
The symptoms of this form of arsenical poisoning are those of a powerful 
hemolytic agent. They appear after an interval, sometimes a few hours, some- 
times a day or two, according to the size of the dose, and are characterized by 
anoxemia, nausea, vomiting, pain in the epigastrium, headache, dizziness. The 
urine is dark, from the color of tea in mild cases to a Burgundy red in the more 
serious. Albumen and casts appear later, and in serious cases the urine becomes 
scanty with complete suppression in fatal cases. Somewhat later than the changed 
color of the urine jaundice appears with pain and tenderness in the liver region. 
It is a hematogenous jaundice from the destruction of red corpuscles and the 
accumulation of pigment in the circulating blood. A blood count shows anemia, 
sometimes very marked, and usually a proportionate fall in the hemoglobin, or 
the color index may be low. If the case goes on to recovery, the urine regains its 
normal color, but albumen may persist for some days, and long after the acute 
symptoms have disappeared the anemia still is demonstrable. Wignall330 has 
found arsenic in the urine eight weeks after the accident. In fatal cases the man 
may pass into a typhoid state with delirium followed by coma, and there may be a 
general bronzing of the skin. Hemorrhagic nephritis and hemorrhagic inflam- 
mation of the liver are found at autopsy. The mortality in industrial cases is 
something over 36 per cent. (Glaister89). 
One of the commonest sources of arsine is the cleaning of the sludge from 
tank cars or storage tanks which have held sulphuric acid, after they have been 
emptied and flushed with water191. Strong acid does not attack the metal, but 
dilute acid does, and if there is arsenic in either acid or metal, the dilution with 
the wash water allows the acid to attack the metal, liberating nascent hydrogen. 
Other sources are the spontaneous decomposition of ferrosilicon, the use of a 
galvanized zinc-coated pail in dipping out acid sludge, producing hydrogen for 
filling toy balloons by treating zinc dust with hydrochloric acid, reduction of 
nitro compounds to amino in dye works, acid pickling of arsenic-contaminated 
Vol. IV. 944 PHOSPHORUS 
625 
metals295, cyanide process for recovering gold and silver, work in chemical lab- 
oratories, the last probably the most important of all. 
The latest source of arsine in industry seems to be cadmium production from 
zinc-cadmium ore which carries arsenic. Acid is used in the leaching of the 
finely ground ore, and cases of arsine poisoning have occurred. 
Selenium and Tellurium 
Selenium and tellurium often occur together as in electrolytic tank sludge and 
have much the same physiological action, with this difference, tellurium inhibits 
sweat, selenium does not. Both cause a garlic odor to the breath before any 
symptoms of poisoning have occurred. Selenium is used chiefly in glass and 
pottery manufacture, also as a catalyst and in making photo-electric cells. Tel- 
lurium has assumed importance during the war, for it can be used to strengthen 
steel288. Mead and Gies215, examining men engaged in recovering pure lead, 
copper and zinc by electrolysis, found symptoms such as these to be common; 
dryness of the mouth with metallic taste, scaly, itching skin, anorexia, nausea, 
vomiting, somnolence. Drowsiness and apathy they found to be the most strik- 
ing symptom. 
Halter114 described a case of industrial selenium poisoning in a paint mixer, 
who had severe skin lesions, edematous erythema on the exposed surfaces, en- 
largement of the liver, porphyrinuria. Selenium was detectable in the urine. 
A case of poisoning by hydrogen selenide in a chemist engaged in its produc- 
tion has been reported from Germany186. Aside from the garlic breath the symp- 
toms consisted in lacrymation, coryza, hoarseness, dyspnea, a purple rash on both 
cheeks and abundant moist rales over both lungs. The last subsided slowly; the 
rash lasted io days. Dyspnea and cyanosis continued, and thrombophlebitis in 
the right calf developed on the 22nd day. On the 52nd day the electrocardio- 
gram revealed a definite lesion of the heart. Selenium could not be found in 
measurable amount in the urine. 
Phosphorus 
Phosphorus, once the most dreaded and spectacular of the industrial poisons, 
is now almost negligible. The effects of phosphorus poisoning in match makers 
were so visible and so distressing to see that the sympathies of the public were 
enlisted readily in the efforts to combat it and after all forms of governmental 
regulation had been tried, and it had been proved that the only way to put a 
stop to phosphorus poisoning was to abolish the use of white phosphorus in the 
making of lucifer matches, the principal civilized countries adopted this very 
Vol. IV. 944 626 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
radical procedure, and now the making and sale of white phosphorus matches is 
carried on only in the Orient117. 
White phosphorus, lucifer matches were made first in 1833, and the disease 
known as “ phossy jaw ” was reported first by Lori'nser of Vienna in 1845. Soon 
after that, cases were discovered in practically all European countries and in 
the United States. The reason for the widespread attention given to this form 
of occupational disease is not its great prevalence, for only a minority of those 
exposed suffer, 70 among 600 workers in Silesia in 20 years, 70 among 620 in 21 
years in France, nor because it is so deadly, the mortality is from 2 to 20 per 
cent., nor because it is rapid and violent in its manifestation, for it is slow to an 
unusual degree, but because it is extremely painful; it attacks the bones of the 
jaw and results in great deformity, which is visible to everyone, and it is ac- 
companied by a fetid discharge, which makes the victim a misery to himself and 
others. The essential factor in phosphorus poisoning is the action of the fumes 
on the periosteum, almost always of the maxillae, to which they gain access after 
removal of a tooth. Necrosis sets in and then a suppurative process caused by 
secondary infection through the pus organisms present in the mouth, then ab- 
scess formation, fistulae and the cachexia of chronic septicemia. Victims of 
“ phossy jaw ” in extreme cases die of this septic process; in slower cases they 
are likely to develop tuberculosis. Exceptionally the periosteum of other bones 
is attacked, and there may be fragilitas ossium. 
The match now made is the safety match, for which amorphous, red phos- 
phorus is used, and the “ strike anywhere ” match, made with the sesquisulphide 
of phosphorus, neither of these having the poisonous properties of white phos- 
phorus. In a French match factory Nicolas and his colleagues237 found that 
there was a great deal of skin disease from the handling of phosphorus sesqui- 
sulphide. It was a rapidly developing erythema with formation of vesicles or 
pustules and accompanied by severe subjective sensations and sometimes, by 
conjunctivitis. Greasy skins were most susceptible. They produced in volun- 
teers an eruption with the paste and also with the powder. A wash of potassium 
permanganate and sodium bicarbonate caused prompt recovery. 
Cases of phosphorus poisoning, however, have been reported from other in- 
dustries, chiefly the production of phosphorus, in the chemical industry, in the 
manufacture of phosphor bronze and in making lights for miners’ lamps. In 
Great Britain most of the cases of phosphorus necrosis coming to the knowledge 
of the factory Inspection Department have occurred in the production of phos- 
phorus. 
A sudden and unexpected reappearance of severe phosphorus necrosis took 
place in the United States in 1923-26, when a new kind of fireworks was manu- 
factured in three factories on the Atlantic seaboard with the use of white phos- 
Vol. IV. 944 CYANIDES 
627 
phorus. The management was ignorant and reckless, and as a result 14 workers, 
all but 1 being women, had developed extensive necrosis of the jaw, and 2 had 
died of septicemia. The period of exposure was short, only 6 months in 1 case. 
So far as is known, this kind of fireworks no longer is made (Ward323). 
Phosphorretted hydrogen, phosphine, PH.A, sometimes is encountered in the 
production of acetylene and also in the use of an acetylene torch supplied with 
impure gas. It is found also in the decomposition of ferrosilicon (see AsH:j) un- 
der the influence of moisture (Brezina and Teleky22). It is excessively toxic, re- 
sembling arsine in its action except that it is not hemolytic (Baader9). Car- 
lisle33 in an article on pulmonary edema in war plants mentions among the 
“ noxious agents ” which may cause such a condition, phosphorus oxychloride, 
trichloride and pentachloride. 
Cyanides 
Cyanides, sodium and potassium, are used on a large scale in industry espe- 
cially in electroplating, cleaning and coating silver, case-hardening steel and iron 
and tanning, and as fertilizer calcium cyanide is used. Another important use 
is the production of hydrogen cyanide for the fumigation of ships and dwellings 
and the destruction of plant parasites. 
These are asphyxiant poisons with a direct toxic action on the body cells re- 
tarding or stopping oxidation. Yet in spite of their dangerous character they 
are used in enormous quantities in industry and with apparent recklessness with- 
out any demonstrable harm to the users. We have been in automobile factories, 
where piles of sodium cyanide lay on the floor near the case-hardening furnaces 
and were shovelled into the furnace like so much coal, yet nobody had ever heard 
of any harm coming from it. Acute poisoning from cyanides does occur from 
time to time, but it is very rare. One of us (R.T.J.) was told of an accidental 
poisoning by cyanide dust involving 3 sprayers of insecticide, 1 of whom was 
found dead, the other 2, unconscious. 
Chronic cyanide poisoning is an even greater rarity, though cases have been 
reported117. 
Acrylonitrile or vinyl cyanide, (CH.CHCNCOOII), is a new industrial com- 
pound, important in the production of synthetic rubber. Tested by the Public 
Health Service59, it was found to resemble hydrocyanic acid very closely in its 
toxic action. On the basis of its cyanide content the Service has suggested 20 
parts per million as the maximum allowable concentration for acrylonitrile. 
These investigators have devised a test for the early detection of absorption, 
which depends on an increase of thiocyanate in the urine and in the blood stream. 
Acrylonitrile, like hydrocyanic acid, renders the tissue cells incapable of oxy- 
Vol. IV. 944 628 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
gen absorption, because an enzyme, which presumably makes this possible, has 
been destroyed. Animals vary greatly in susceptibility to it. These are the 
symptoms in man in the order of their appearance; flushing of the face, increased 
salivation, irritation of eyes and nose, respiration, at first rapid and deep, then 
shallow. 
In animals the same sequence is found, and flaccid paralysis may follow, 
but it is transient. Severe convulsions may occur under heavy exposure yet not 
cause death. Administration of sodium nitrite doubles an animal’s resistance, 
for it forms methemoglobin, which has an affinity for the nitrile molecule and 
removes it from the blood. 
Wilson339 has found that, in spite of elaborate precautions in synthetic rub- 
ber plants, mild exposure to acrylonitrile does sometimes happen and causes 
nausea, vomiting, weakness, occasionally headache and diarrhea. In several cases 
he saw mild jaundice, severe in one case and lasting four weeks. Usually the 
jaundice was accompanied by a low-grade anemia, 4,000,000, with leucocytosis 
of 12,000 but with a normal differential count. Urinanalysis was negative ex- 
cept for an increased bile content. 
Industrial Solvents 
These are the solvents used for natural gums, shellacs, resins, rubber, gutta 
percha; for the newer cellulose compounds, nitrate and acetate, used in making 
lacquers, dopes for fabrikoid, waterproofing, artificial leather, patent leather; 
for celluloid and nonshatterable glass; for fats, oils, greases, in degreasing ma- 
chine parts and in dry cleaning and also as thinners for coatings and as removers 
of coatings. 
The properties that govern the choice of a solvent are its ability to dissolve 
these substances more or less readily and its volatility, for it must evaporate fairly 
quickly to be practically useful. One other property is important, inflammability, 
for that influences insurance rates. This works to the detriment, fortunately, of 
one of the most dangerous solvents, coal tar benzene (benzol), but not to the 
detriment of the chlorinated hydrocarbons, which are being pushed actively, be- 
cause they are not inflammable. 
The solvents that are important to the toxicologist are avid for fats and vola- 
tile, their danger being in direct relation to these two characteristics. The more 
volatile the solvent, the quicker and more intense the contamination of the air 
in the workroom; the more avid for fat, the greater the affinity for the fats of the 
body, those of the blood and the central nervous system. This being true, it 
behoves physicians to look with suspicion on any new solvent, which is very 
efficient and a very quick drier. 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
629 
Aliphatic or Petroleum Series of Solvents 
Alcohols 
Of the members of the aliphatic series used in industry, only the most im- 
portant can be described. Methyl or wood alcohol was for many years a source 
of grave injury to industrial workers. Tyson and Schoenberg319 estimated in 
1915 that no less than 2,500,000 workers in the United States came in contact 
with wood alcohol in the course of their work, and they found about 100 cases 
of industrial poisoning caused by inhalation or skin contact. It was peculiarly 
an American poison. Up to 1906 the use of grain alcohol in industry was not 
lawful in the United States and denatured alcohol, so commonly used in Europe, 
was unknown in American industry; therefore methyl alcohol was the customary 
solvent, and all the prejudices of the practical man were in its favor. The strik- 
ing cases of industrial poisoning, which served to bring about the change in leg- 
islation providing for revenue-free denatured alcohol, occurred in the varnish- 
ing of the interior of beer vats (Patillo247, Casey Wood346,347, Hale112) and in the 
stiffening of felt hats by means of wood alcohol shellac. 
It is the effect on the eyes which makes methyl alcohol a poison to be spe- 
cially dreaded. According to Lewin189 there is no other industrial poison which 
has so sure and specific an action as the action of methyl alcohol on the optic 
nerve. Characteristically, the impairment of sight clears up partially for a pe- 
riod, giving hope of recovery, only to increase again and leave the victim blind 
in one or both eyes. DeSchweinitz284 and Tyson318 call it an optic neuritis, in- 
flammation of the connective tissue of the optic nerve, which subsides but is fol- 
lowed later by atrophy. Holden140 and Friedenwald84 believe it is primarily a 
degeneration of the ganglion cells of the retina. Jeliffe155 has reported two cases 
of multiple neuritis in painters using wood alcohol varnish. 
A typical case, one rarely seen nowadays, came under the observation of one 
of us (R.T.J.). After working for three days cleaning a vat with a trade name 
product containing methanol, a workman became acutely sick, vomited, com- 
plained of gastric pains and blurred vision. He recovered quickly from all symp- 
toms except the last. He is now almost totally blind. 
The experience with bootleg liquor during prohibition in the United States 
made so profound an impression that methyl alcohol was almost driven out of 
industrial use and even now is regarded with an apprehension which it does not 
deserve. Sayers, Young and Schrenk274 found that dogs suffered no injury to 
the optic nerve nor any other significant effect after being exposed 8 hours daily 
for 379 days to 450 to 500 parts per million. Four pups born during the experi- 
ment were normal. 
Vol. IV. 944 630 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
The higher alcohols give no trouble in industrial use. Theoretically the 
toxicity of the alcohols rises as the series goes up. If one goes by the results of 
intravenous injections of animals with the members of this series one finds tox- 
icity mounting, from methyl to ethyl, propyl, butyl, amyl. This is Richardson’s 
law, but it is of no use to the industrial toxicologist, who does not go by intra- 
venous injections but by the breathing of contaminated air. Alcohols above ethyl 
have too low a volatility to poison the air unless heat is used. Amyl alcohol, the 
most dangerous according to Richardson, is the least volatile, while methyl, the 
safest, according to him, is the most volatile, and it is the only one that practical 
experience has shown to be dangerous. That is, no case has been recorded in 
which one of the higher alcohols used alone was responsible for occupational poi- 
soning, but there are cases of narcotic poisoning from mixed fumes containing 
one of the higher alcohols, and it may be that in combination with other nar- 
cotics they may play an important part. 
Acetates 
For the acetates experience seems to show that methyl acetate is the least 
narcotic but somewhat more irritating to the eyes and the upper air passages 
than the higher members of the group. It has been known to cause a tight feel- 
ing in the chest and breathlessness. Ethyl acetate is more narcotic than methyl, 
although Zangger352 regards it as the safest of all the organic solvents. Normal 
and isopropyl acetates have given no trouble so far as is known. Normal butyl 
and amyl acetates are about the same in irritating and narcotic properties, but 
butyl is 25 per cent, more volatile than amyl. Both are more active than the 
lower acetates and may cause burning of eyes, nose, throat, cough, tightness in 
the chest, bronchial catarrh, headache and indigestion, as has been known for 
years. Many men and women can use it without even discomfort, and both Ger- 
man and British factory inspectors after careful study can find no constitutional 
disturbance traceable to butyl or amyl acetates although one fatal case in 1930 
followed the use of a mixed solvent containing amyl acetate. 
Acetones: Ketones 
When one reads the literature on acetone, one finds much about its narcotic 
action, but here again it is a question of laboratory animals, not human users. 
Acetone has an innocent history so far as its industrial use is concerned. Robert164 
said that it was almost inconceivable that poisoning could follow its use. Green- 
berg and his colleagues102 investigating factories in New York State, where an 
acetone-methanol solvent was used in making “ fused collars ”, found that the 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
631 
air contained 40 to 45 parts per million of acetone. They examined 19 workers 
but, though acetone was found in the urine of all, no clinical symptoms nor blood 
changes were found. 
Acetone is dimethyl ketone. Now there is also methylethyl ketone, called 
butanone, and methylpropyl ketone or pentanone. The Public Health Service 
has tested these and several others of the group and finds that all are narcotic, 
depressant to the body temperature, the respiratory and the heart rate; all abolish 
corneal, auditory and equilibratory reflexes, the action in the straight chain 
methyl ketones being proportional to the number of carbon atoms in the chain. 
Aldehydes 
Formaldehyde, acetaldehyde, croton aldehyde, paraldehyde and allylaldehyde 
or acrolein all are used in industry, but only the first and last are of importance. 
Formaldehyde is used in enormous quantities, especially in the production of 
plastics, of which bakelite is the best known. Workers exposed to the fumes suf- 
fer from local irritation of eyes, throat, nasal passages, skin, but an effect on the 
deeper air passages is seen rarely. There is, of course, a wide variation in in- 
dividual susceptibility, and some men cannot work in an atmosphere quite tol- 
erable to others. This is true both with regard to skin eruptions and inflamma- 
tion of eyes and mucous membranes. Cases have been reported of keratitis, 
corneal ulcers, dimness of vision, painful skin lesions, bronchopneumonia, asth- 
matic attacks, even temporary insanity, all attributed to formaldehyde, but in 
all of them other chemicals were present, phenol, methyl alcohol, “ hex ”, turpen- 
tine, benzene. It is notoriously a strong sensitizing agent. Patch tests should 
not use even 5 per cent. 
Acrolein is allylaldehyde, an extremely irritating gas, given off by the heat de- 
composition of fats. Lewin190 and Iwanoff152 found it more toxic than formal- 
dehyde, and Koelsch167 described two cases of poisoning, one fatal, in men using 
an oxyacetylene torch on the inside of a tank car which had contained rape seed 
oil. The commonest sources of this gas are melting old stereotype plates cov- 
ered with oily ink and making soap and candles. 
Glycols: Cello solves: Dioxan 
Glycols are assuming more and more importance as solvents for coatings, 
printing inks, plastics. They are diatomic alcohols containing two HO groups, 
and there is a long list of glycols and their derivatives, many of them industrially 
useful. They are not volatile at room temperature, and poisoning has occurred 
only when heat has been applied. 
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INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
The glycol, which was used as a vehicle for the notorious sulfanilimide elixir, 
was diethylene glycol. In animal experiments, when administration is by mouth 
or under the skin, the glycols have the same action as had the elixir, namely, 
severe damage to the kidneys. In industrial use, where it is a case of breathing 
fumes, the picture is different, the symptoms pointing to an action on the central 
nervous system and the bone marrow. Chronic intoxication by glycols in ani- 
mals has been studied by Morris, Nelson and Calvery229, who found ethylene and 
diethylene glycol the most toxic, producing calcium oxalate stones in the kidneys. 
Propylene glycol apparently was harmless. 
The best known members of the group are ethylene glycol monoethyl ether, 
known as cellosolve, and the monomethyl compound, methyl cellosolve. Carbitol 
solvent is diethylene glycol monoethyl ether. Cranch, Smyth and Carpenter45 
say it is less irritating to the skin than glycerine, less likely to set up cutaneous 
allergy. The ethylene glycols were tested by the Public Health Service326. Ani- 
mals given a lethal dose showed congestion and edema of the lungs, congestion 
of the kidneys, petechial hemorrhages in the gastric mucosa. However, Green- 
burg100 was able to declare in 1938 that no cases of industrial poisoning from the 
monoethyl compound, the cellosolve, had come to light, and this seems to be true 
in England also (Browning23), although it has been used extensively in spray 
painting. 
Methyl cellosolve has a different history, perhaps because its use in industry 
has required the application of heat causing volatilization. It came into use as 
a solvent for the stiffening material used on shirt collars in the so-called “ tru- 
benizing ” or “ fusing ” process. This requires pressing with a hot iron, while 
the ordinary uses of glycol solvents require no heat. In 1936 Donley53 reported 
a case of toxic encephalopathy in* a woman employed in a shirt factory pressing 
fused collars. In addition to the brain symptoms she had anemia, 3,500,000 red 
blood cells, hemoglobin 85 per cent., lymphocytes 46 per cent. The solvent con- 
tained methyl cellosolve but only 3 per cent. 
Greenburg’s100,101 cases were more convincing, for the solvent to which the> 
were exposed contained 33 per cent, methyl cellosolve. He reports an investiga- 
tion of 19 young men employed in making fused collars, 2 of them acutely ill 
with severe anemia of the aplastic type, tremors, marked mental dullness, 1 with 
a history of multiple neuritis and abnormal neurological findings and 16 with ab- 
normal blood pictures. In this last group there were 4 with abnormal reflexes 
and tremor of the hands and 4 with the above signs exaggerated and in addition, 
symptoms of drowsiness and fatigue. Greenburg advises careful blood examina- 
tion for the detection of intoxication in an early stage. The picture is one sug- 
gestive of macrocytic anemia with reduction of platelets and the appearance of 
young granulocytes. It may be mistaken easily for benzene poisoning. 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
633 
Diethylene dioxide or dioxan, the second ether of ethylene glycol, came into 
use as a solvent in the early thirties, and at first it was looked upon as compara- 
tively safe. The Bureau of Mines350 tested it in 1930 and found it of compara- 
tively low toxicity but with a locally irritating action so intense as to provide 
ample warning at a point far below that at which serious harm would result. 
However, in actual practice such warnings are not always heeded, and in 1934 
Barber10 published the story of 5 fatal cases in workers who died after an acute 
illness lasting 5 to 8 days. They had inhaled fumes with greater content of the 
toxic substance than ever before because of a change in the apparatus and had 
suffered from smarting of nose and eyes, headache, drowsiness, dizziness, an- 
orexia and nausea but had kept on working. Within a fortnight all were seri- 
ously ill with severe gastric symptoms, liver enlargement without jaundice, 
anuria and uremic coma. Autopsy on 4 of the 5 revealed hemorrhagic nephritis 
and necrosis of the liver. 
Animal tests were made after this, and it was found that dioxan produces 
damage to liver and kidneys of guinea pigs, rats and rabbits. Wirth and Klim- 
mer343 say that it may produce paralysis, and damage to the blood forming 
organs also. 
Studies made by the Public Health Service239 on the effects of repeated ex- 
posures of rats to vapors of glycol ethers, 300 to 400 parts per million, show that 
“ small but measurable effects ” on the cellular elements of the blood appear, such 
as increase in young granulocytes, decrease in hemoglobin concentration and red 
cell count. They agree with Greenburg that examination of the blood will yield 
the earliest warning of poisoning. 
Furfural 
Furfural is about one third as toxic as formaldehyde, dose for dose, but prac- 
tically it is far less harmful, since it is a fairly nonvolatile liquid, while the lat- 
ter is a gas. Korenman and Resnick171 found in a factory in Odessa, where the 
air contained from 0.007 to 0.053 mgm. per liter, that there was a complaint of 
red, weeping eyes, itching of the throat and headache. It is said to cause anaes- 
thesia of the cornea. 
Ether 
Sulphuric ether is used in this country chiefly in the production of photo- 
graphic films and of smokeless powder and military gun cotton. During World 
War I there were many cases of acute ether intoxication among the young women 
employed here and in England but never of a serious character. An interesting 
and thus far unexplained feature of this was a polycythemia with red counts 
Vol. IV. 944 634 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
running from 5.5 to 7.8 million in over one half of those examined222. In Ger- 
many two severe cases of ether poisoning, one fatal, were caused by spilling ether 
in a factory making collodion films with ether-alcohol solvent22. 
Metol 
Metol, which is methyl-p-amido-m-cresol sulphate, has been used for many 
years in photography, where it is notorious for producing eczematous or ulcera- 
tive lesions on the skin and eyelids. 
Nitroglycerine 
Nitroglycerine produces its well known effects on workmen who are new to 
the job, but the majority acquire a transient immunity to it. No form of chronic 
poisoning has ever been discovered among nitrators of glycerine or makers of 
dynamite and mixed powders (Ebright63, Heitz134). 
Oxalic Acid 
Grolnick105 has described a case of early gangrene of the fingers like that 
caused by phenol in a man who used oxalic acid at intervals for two years in floor 
cleaning. Howard’s case142 was one of inhalation of steam from hot oxalic acid 
in a man who cleaned automobile radiators by boiling them in a strong solution 
of the acid. There was inflammation of the nose, throat and air passages, nose- 
bleed, obstinate cough, vomiting, bloody stools, gradual emaciation and increas- 
ing weakness. An intense pain in the back was the chief complaint, and there 
was albumen in the urine, but apparently no microscopic examination was made 
of either urine or blood. 
Hexamethylenetetramine 
Hexamethylenetetramine, also called “ hexamine ”, “ hex ” or “ urotropin ”, 
is an excellent accelerator for rubber vulcanization, but it is so markedly irri- 
tating to the skin of a large proportion of individuals that its use has been prac- 
tically abandoned. No instance of the familiar action on the kidneys has ever 
been noted in industrial cases. 
Acetylene 
When an acetylene welder suffers an attack of “ gassing ”, the cause must be 
sought either in the metal he is welding or in some accidental impurity in the 
gas. According to Legge183 29 cases of gassing in connection with the use of 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
635 
acetylene torches were notified between 1921 and 1931, 20 of them in welders, 
rivetters, etc., when possibly such substances as zinc oxide from galvanized iron 
or naphtha fumes from bituminous paint or carbon monoxide may have been the 
active agents. Nine cases were caused by acetylene gas leaks and were charac- 
terized by vertigo, headache, mild gastric symptoms, semiasphyxia, loss of con- 
sciousness for brief periods. The impurities that may be present in acetylene 
gas include phosphine, arsine, hydrogen sulphide, carbon disulphide and carbon 
monoxide. Impure acetylene may contain as much as 0.17 mgm. per liter of PH3 
and 0.25 mgm. per liter of H2S according to Adler-Herzmark1 who saw a case of 
jaundice with glycemia in an acetylene welder. 
Chlorinated Hydrocarbons 
These solvents, which are non-inflammable as well as strongly solvent, have 
a wide and increasing use as degreasers of metal, cleansers of textiles, solvents for 
rubber, tar and gums, thinners for cellulose lacquers and in treatment of garbage, 
tankage and bones. Other uses are the production of high grade lubricating oils 
from inferior stock, the production of edible and non-edible vegetable oils, the 
purification of explosives and for refrigeration. 
The chlor compounds may be divided into three groups, namely, the saturated 
(paraffin) group, methane, etc.; the olefins, unsaturated ethylene, propylene, 
etc.; the naphthalenes. The following list includes those compounds which are 
of more or less importance in industry. 
Saturated Compounds of the Methane Series 
Common Name 
Chemical Name 
Formula 
(i) Methyl chloride 
Monochlormethane 
CH3C1 
(2) Chloroform 
T richlormethane 
CHCI3 
(3) Carbon tetrachloride 
Tetrachlormethane 
CC14 
(4) Ethyl chloride 
Monochlorethane 
C,H5C1 
(5) Ethylene dichloride 
Dichlorethane 
c2h4ci2 
(6) Ethylene trichloride 
Trichlorethane 
c2h3ci3 
(7) Acetylene tetrachloride 
Tetrachlorethane 
c2h2ci4 
Unsaturated Compounds of the Methane Series 
(8) Acetylene dichloride 
Dichlorethylene 
c2h2ci2 
(9) Acetylene trichloride 
Trichlorethylene 
c2hci3 
(10) Tetrachlorethylene 
T etrachlorethylene 
C2C14 
(n) Halowax 
Chlorinated Naphthalenes^ 
C10H5C13 
from Tri to Hexa ( 
C10H2C16 
Vol. IV. 944 636 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
It is necessary that the common as well as the chemical names be known, for 
the former often are very misleading. The unsaturated group is less toxic than 
is the saturated group, and if we should go by the names commonly used in indus- 
try, we should class certain highly toxic compounds of the saturated group among 
the comparatively harmless unsaturated ones, as, for instance, tetrachlorethane, 
which is known as acetylene tetrachloride, or dichlorethane, known as ethylene 
dichloride. 
Of these, Nos. 1, 3, 5, 7, 9 and n, are industrially the most important. 
As to the comparative toxicity of the members of the first group von Oettin- 
gen240 says that the narcotic action increases with the number of chlorine atoms, 
but that data are not available concerning the connection between liver damage 
and the number of chlorine atoms. However, back in 1915 Evarts Graham96 
declared that experimental necrosis of the liver increased in animals with the 
increase of chlorine atoms, being brought about by a smaller dose of CC14 than of 
CHC13 and much smaller than that of CH2C12. 
On the basis of animal experiments carried on till death came, Matruchot203 
gives the comparative toxicides as follows: trichlorethylene 1.0, per (tetra) chlor- 
ethylene 1.4, dichlorethylene 1.5, dichlorethane 1.6, carbon tetrachloride 2.6, 
chloroform 4.2, trichlorethane 5.0, tetrachlorethane 6.0. 
The unsaturated group is highly narcotic but does not give rise to degenerative 
changes in the liver as do the members of the saturated group (Barrett and asso- 
ciates11, Hammes122). 
Henderson and Haggard136 lay stress on the great difference between the anes- 
thetic action and the more subtle toxic action, which may be produced from con- 
centrations too small to cause anesthesia and, therefore, insufficient to give warning 
of danger. The personal equation plays a large part in cases of intoxication by this 
group of solvents. It is not rare to have a large number of workers using carbon 
tetrachloride or trichlorethylene with no apparent discomfort, and suddenly one of 
them develop symptoms of intoxication without any increase of exposure. Pa- 
gniez246 reported 3 cases, all exposed to the same fumes of CC14 for the same length 
of time, one of them mild, one severe, one fatal. 
Carbon tetrachloride or tetrachlormethane (CC14) is industrially the most im- 
portant member of this class. It is familiar to the public as a chemical fire extin- 
guisher and as a non-inflammable dry cleanser, to the medical world as an anthel- 
mintic. A great deal of experimental work has been done on this compound both 
in connection with its therapeutic use and its use in industry, but the cases of intoxi- 
cation have come chiefly from its industrial use. It is a narcotic with an action very 
like that of chloroform though not so strong. On the other hand the after-effects 
of severe narcosis seem to be more serious than are those of delayed chloroform 
poisoning, and they occur more often. 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
637 
Industrial poisoning from CC14 is typically acute with symptoms of narcotic 
intoxication, followed by symptoms pointing to liver and kidney damage, which 
appear after an interval of about 6 to 24 hours. In the early days of anthelmintic 
therapy there were a number of accidents because certain persons proved to be 
very susceptible to the action of CC14. These were chronic alcoholics, peopfe with 
damaged hearts and kidneys and those with malnutrition especially from a low 
calcium diet. Animal experiments showed that the attack is especially on the 
intestinal tract and the liver, much less on the kidneys, that a negative calcium 
balance increases the susceptibility and that alcohol increases its action, as does 
also a fatty diet just before the dose (Lamson and associates176’177’178). In man, 
when CC14 is given by mouth, much the same results are produced, but in industrial 
cases, which follow inhalation, the symptoms of renal damage overshadow those 
of hepatic injury. The history is usually the following; nausea, vomiting, abdom- 
inal pains, diarrhea, headache, dizziness, then dark colored urine, which often is 
the first thing that sends the man to his doctor, and later on jaundice, then increas- 
ing oliguria with the urine loaded with casts and albumen. Complete anuria may 
last for some days, 10 in Dudley’s case58, and then clear up, or it may persist until 
death with symptoms of uremic poisoning. Three cases of nephrosis from CC14 
poisoning, 2 of them fatal, were reported in 1939 by Smetana with an excellent 
review of the whole subject293. 
The latest instance of acute nephrosis is that reported by Corcoran and his 
colleagues43 in a welder, who used carbon tetrachloride to prevent explosion when 
he welded a tank that had held gasoline. These authors find that the form of 
nephrosis is that caused by toxic agents; that it is essentially a process destructive 
of the epithelium of the kidney, the stroma being left intact so that complete recov- 
ery may occur through epithelial regeneration. 
The literature of CC14 poisoning contains some unusual clinical pictures. One 
of Dudley’s58 patients had an exposure of only 5 minutes to heavy fumes from 
a fire extinguisher, but 9 days later he developed epileptiform convulsions, a 
blood pressure of 220/90 and an acute uremia of severe character. He finally 
recovered. 
A fatal case after only hours’ exposure in a large, well-ventilated machine 
room occurred in Germany in 1941. Death was due to pneumonia, which followed 
symptoms of poisoning involving the digestive tract, liver and kidneys. 
A case, not of industrial origin but caused by the use of a “ pyrene ” fire extin- 
guisher in the interior of an automobile, was described by Hagen and his col- 
leagues110. The man inhaled the fumes for about half an hour with no immediate 
symptoms of any severity. He took a couple of drinks of alcohol and had a good 
night but the next morning began to suffer from nausea, vomiting, malaise, diarrhea 
and numbness of hands and feet. Later, grave hepatic and renal damage appeared 
Vol. IV. 944 638 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
with hemolysis and some pulmonary damage. There were also nervous symptoms, 
hiccough, mild convulsive seizures, increased muscle tonus and hyperactive reflexes. 
Recovery came after some 3 weeks in hospital. 
Wirtschafter343 was the first to describe visual changes following intoxication 
of a fairly minor character. Five men, dry-cleaners, who complained of headache, 
dizziness, nausea, vomiting, etc., showed bilateral peripheral constriction of the 
color fields but no central scotomata. Two of them had not noticed any change 
in their vision; the other 3 complained of spots before the eyes, blurring, and 
“ everything looked small ”. Wirtschafter, acting on Lamson’s experimental find- 
ing that a fall in blood sugar occurs in animals treated with CC14, made blood 
sugar tolerance analyses and found the amount in all 5 men to be at the lower 
border of the normal variation and sometimes below this. There were small 
amounts of sugar in the urine after fasting, which increased after the giving of 
glucose, and both the blood and the urine returned to normal, when the men left 
work and were put on Minot’s diet of calcium and dextrose220. He suggests that a 
routine examination of the peripheral visual field may be useful in revealing intoxi- 
cation at a very early stage. H. F. Smyth298 agrees with this. Among 93 men 
whom he examined he found 10 with the visual field restricted as much as 30 per 
cent, toward the bottom and outer edge and .16 with less certain evidence. 
Other atypical and dubious forms are those, which are predominantly nervous 
in character. Andre Domart in a Paris thesis written in 1938 describes cases of 
polyneuritis following a hepatorenal type of poisoning. A case of progressive spinal 
muscular atrophy is attributed by Kinney162 to carbon tetrachloride poisoning. 
Hagen’s109 patient had a series of severe epileptiform attacks, coma and convul- 
sions, which began on the eighth day following acute intoxication while cleaning a 
filter with CC14. 
Chronic poisoning, developed gradually in the course of prolonged exposure to 
small quantities of CC14, is much rarer and less characteristic. Butch30 had a case, 
which belongs in this class, one with symptoms simulating portal cirrhosis, a condi- 
tion which Bollman and Mann had produced in dogs. Poindexter and Greene259 
found at autopsy on a workman, who had experienced long exposure to carbon- 
tetrachloride, cirrhosis of the liver with ascites and infarction of the right kidney 
and compensatory hypertrophy of the left. 
For a long time fairly high concentrations of carbon tetrachloride, even up to 
1,000 parts per million or higher, were considered as allowable in industrial estab- 
lishments. However, more than io years ago P. A. Davis49, who has had a long 
and extensive experience with the use of this solvent by the Goodyear Rubber 
Company, decided that anything over ioo parts per million is dangerous for con- 
tinued exposure, and that figure has been approved tentatively by several state 
codes as the maximum allowable concentration. Even though this standard is 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
639 
adhered to, Davis advises a careful selection of workers with rejection of the obese 
and the undernourished, nephritics, diabetics, those with lung or liver pathology 
and those having an enlarged thymus or thyroid. He warns of the possibility that 
free chlorine or hydrochloric acid may be present in commercial CC14 and cause 
bronchitis or bronchopneumonia. Elkins66 of Bowditch’s staff in Massachusetts 
and Heimann and Ford133 of Greenburg’s in New York have found mild symptoms 
of narcosis in workers where the concentration of CC14 was lower than 100 parts per 
million. Elkins thinks that this level is too high, that the limit should not be over 
50 parts per million. 
Carbon tetrachloride, in spite of its unpleasant odor, has in some men a pleas- 
antly intoxicating effect, and cases of addition have occurred in Germany and in 
this country. 
E. F. Russell270 believes that women are more susceptible to carbon tetra- 
chloride than men, that cigarette smoking increases their susceptibility, and that 
one result is abnormally frequent menstruation. 
Trichlorethylene. — Next in importance industrially comes trichlorethylene, 
which can serve the same purpose as CC14 in many cases, and often is preferred 
to the latter as less toxic. For some years after its introduction it was recom- 
mended as an ideal non-inflammable and non-poisonous degreaser and lacquer 
thinner, but evidence from England and Germany soon proved that it is a strong 
narcotic and even pointed to serious systemic damage. In England 38 cases of 
severe acute poisoning with 3 deaths from the industrial use of trichlorethylene 
had been reported to the Home Office by 1935. From Denmark came 5 cases. 
Much the most important publication in this field came from Germany, the mono- 
graph by Katharina Stiiber304, which appeared in 1931 and recorded 284 cases 
with 25 deaths. Von Oettingen240 collected from the literature 7 additional fatali- 
ties between 1931 (Stiiber’s date) and 1937 and 8 non-fatal cases. Pies256 in 
1939 added 2 more cases to the German list of victims of trichlorethylene poison- 
ing, both in women who fell unconscious while at work. One recovered fairly 
soon, but the other was unconscious and cyanotic for some time and developed 
bronchiolitis and bronchopneumonia with fever. 
The most striking characteristic of trichlorethylene'is its acute narcotic action. 
Lehmann184 says it is to chloroform as i .7 to i .0. By far the larger number of cases 
in man are acute in character. In Stiiber’s list of 19 fatal cases, whose history 
was known, 12 were acutely narcotized and died without regaining consciousness. 
Three fatal cases in the German factory inspectors’ reports of 1935 belong in this 
class. Of the 39 English cases all but 2 were severely narcotized; 3 died; the 
others recovered completely. That recovery without lasting injury is to be ex- 
pected is shown in the study made by Striker and his colleagues303 of the histories 
of 304 patients on whom “ tri ” was used as an anesthetic. 
Vol. IV. 944 640 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Stiiber’s list contains cases not only of acute narcotic intoxication but of 
chronic poisoning with marked damage to the central nervous system especially 
but also to the vascular system and to the liver, spleen, lungs and kidneys. Her 
report aroused much interest and started a controversy that still goes on. While 
it is certainly true that organic injury is seen rarely in cases of industrial tri- 
chlorethylene poisoning, some cases have been reported. 
Practical experience with this solvent shows that it causes more discomfort, 
more minor complaints among workers, especially women, than does “ tetra ”, 
because of its strong narcotic action. In hot, humid weather especially there will 
be many cases of headache, dizziness, confusion and fainting, but the severe symp- 
toms pointing to organic damage, which sometimes follow acute CC14 poisoning, 
appear only rarely. Willcox335 saw a case of toxic jaundice following exposure 
to trichlorethylene, and Browning describes one of jaundice with enlarged liver 
occurring in a lad after six months’ exposure to “ tri ” 24. 
Reports of severe damage to the central nervous system come from Germany; 
Kunz and Isenschmidt174 describe a case of polyneuritis of all four limbs, paralysis 
of the hypoglossal nerve and retrobulbar neuritis in a man of 56 who had worked 
with trichlorethylene for a year, while Persson’s254 2 patients, degreasers, devel- 
oped symptoms of spinal cord injury, spastic ataxia, strongly positive Romberg 
and disturbed sensation in feet, hands and forearms. In Stuber’s report 182 out 
of 284 cases are listed as chronic, and the symptoms cover a wide range; func- 
tional neuroses, paralysis of cranial nerves, epileptoid seizures with psychic dis- 
turbances, anemia, gastrointestinal disorders. On the other hand, according to 
Browning23, John Bridge, the Chief Medical Officer of Factories and Workshops, 
finds little proof of chronic poisoning. Only one case of the 30 reported seems to 
belong in that class, a woman, who for some weeks complained of pain in the 
chest, dyspnea, anorexia and loss of weight. She was slightly anemic. Three 
persons, who had been exposed for a year or more under poor conditions, were 
examined carefully by Bridge for evidence of organic damage, but none was found, 
although all 3 complained of subjective symptoms attributable to a narcotic 
poison. 
Animal experiments tend to confirm clinical evidence that organic lesions are 
rare, although McCord208 found in his experiments very severe lesions in all im- 
portant structures. However, the great majority of workers find no characteristic 
changes in liver or kidneys. Barrett and his colleagues11 compared the toxicity 
of trichlorethylene and carbon tetrachloride, a point of great practical importance, 
since one can be substituted for the other in many industrial processes. They 
found that guinea pigs were very susceptible to organic damage from CC14. Ex- 
posure to 1200 p.p.m. resulted in hemorrhage and in degenerative changes in the 
liver and kidneys. The same exposure to “ tri ” for more than 1,100 hours caused 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
641 
no pathological change in any organ except the liver, and even there it was so 
slight as to be probably of no significance. They agree with Lehmann, however, 
that trichlorethylene is the more powerful narcotic of the two. 
Hammes122 gives the history of an acute, severe intoxication developing sud- 
denly after one day’s work with CC14, in a man who had used trichlorethylene on 
the same job for 3 years without any trouble. In this case there was only slight 
involvement of the liver but marked involvement of the kidneys. 
An unusually severe case of trichlorethylene poisoning was seen by one of us 
(R.T.J.). A man was put to cleaning machine parts in a large tank of “ tri ” in 
a far corner of the plant where ventilation was poor. He soon complained of 
dizziness, and after two hours and a half he fell to the floor unconscious, arriving 
at the hospital comatose. Profuse sweating was noted. He had deep respirations, 
slow but increasing in frequency, a pulse of 86 with blood pressure 102/70. As 
soon as the cause was learned, oxygen was administered, and he recovered con- 
sciousness in half an hour but vomited repeatedly for several hours complaining 
of severe pain in the head and the abdomen. Recovery was complete. Ethel 
Browning24 reports 2 cases of severe anemia, which she tentatively ascribes to 
trichlorethylene, one aplastic in form and fatal, the other, hypoplastic. 
An important and still unsettled point is the specific action of “ tri ” on the 
sensory branch of the trigeminal nerve, which Plessner258 described in 1916, and 
which gained such general credence that trichlorethylene, under the name of 
chlorylen, was widely used to stop the pain of facial neuralgia. Much scepticism 
has, however, developed of late concerning this theory. Plessner’s cases, 4 men 
with complete sensory but not motor paralysis of the fifth nerve, occurred dur- 
ing World War I, when German factories were obliged to use all sorts of ersatz 
material and in a factory where no such form of sickness had ever occurred before. 
All 4 sickened at the same time. Some 12 years later Kalinowsky158 saw 2 men 
with practically identical symptoms, but they had been exposed not to trichlor- 
ethylene but to a mixture containing some unidentified chlorinated hydrocarbons. 
In Stiiber’s 10 cases of trigeminal paralysis, all industrial, there is no proof that 
“ tri ” was the only compound present. Moreover, the therapeutic use of pure 
“ tri ” seems to show that its effect is not paralyzing but only narcotic. Eichert65 
reviewed the literature covering this form of treatment of trigeminal neuralgia 
and could find no evidence that the prolonged use of this drug was followed by 
injury to the fifth nerve, even in cases of addiction. 
Eichert makes the same statement with regard to optic nerve injury, which 
also has been described as characteristic of poisoning from trichlorethylene. In 
Stiiber’s collection there are 9 cases of visual disturbance, ranging from alteration 
of the color sense to optic nerve atrophy. Baader (see Stliber) Saw 2 cases follow- 
ing long exposure. Retrobulbar neuritis following 14 months’ exposure occurred 
Vol. IV. 944 642 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
in a case that was reported to one of us (A.H.) a few years ago, but in none of 
these can we be sure that trichlorethylene alone was the active agent. The same 
doubt arises as to the 2 cases of angina pectoris reported by Gerbis88 and to the 
cases of cerebral hemorrhage (Plessner, Stiiber, Kalinowsky.) Stiiber assumes as 
the cause of these cases a vascular injury such as sometimes follows acute carbon 
monoxide intoxication and results in thrombosis or hemorrhage. 
Koch165 made an autopsy on the body of a workman, who died from breath- 
ing fumes from a hot degreasing kettle in a basement, and he found extensive 
lesions in the respiratory tract beginning in the lower third of the trachea, where 
the epithelial lining was completely desquamated. The alveoli were filled with 
blood cells and fatty epithelial cells. Hansen’s123 case had a similar origin, but 
here there was an extensive tuberculosis. In Christiansen’s41 case, which he re- 
gards as a confirmation of Koch’s, there was a widespread pathological process 
in the lungs resembling in the x-ray picture a miliary tuberculosis. This man 
recovered after 5 months. In all of these cases one must remember the possible 
presence of Cl, HC1, COCl2 and, according to von Oettingen240, of dichlorethane 
in the fumes. 
Trichlorethylene according to Barrett and associates11 is more likely to give 
rise to addiction than is carbon tetrachloride because the fumes are less nauseat- 
ing. The maximum allowable concentration has been placed tentatively at 200 
parts per million, because the margin of safety is distinctly wider than is that 
for CC14. 
Recently an interesting contribution to the action of trichlorethylene has come 
from a non-industrial source. A. M. Geiger87 describes a case of intoxication from 
the therapeutic use of “ tri ”, which was characterized by profound loss of con- 
sciousness and “ multiple focal ventricular tachycardia of an ominous type, likely 
to lead to fatal ventricular fibrillation This condition appeared repeatedly 
under therapeutic inhalations, first of pure “ tri ”, then of pure carbon tetra- 
chloride. Geiger suggests that here may be found an explanation for mysterious 
sudden death occurring from the industrial use of “ tri Confirmation of his 
findings is afforded in a recent publication by Waters, Orth and Gillespie324, call- 
ing attention to cardiac arrhythmias noted by them in io patients and 7 dogs 
during anesthesia with trichlorethylene. Multiple focal ventricular extrasystoles 
and ventricular paroxysmal tachycardia were seen several times among 6 patients 
followed with electrocardiograms. 
T etrachl or ethylene is, according to Lamson, Robbins and Ward178, much safer 
than is CC14 when given by mouth. In their animal tests they found it was ab- 
sorbed from the gastrointestinal tract only if a large amount of fatty food had 
been eaten just before. Autopsy on animals, which had reecived it by inhalation, 
showed no fatty degeneration in the organs. These authors believed it to be the 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
643 
safest member of this group for therapeutic use. The experiences of Fernando 
and his colleagues in India is in harmony with Lamson’s findings. They tested 
the toxicity of tetrachlorethylene on hi patients, finding “ no appreciable toxic 
effect on the liver in any of them, even in those receiving double the maximum 
adult dose in general use ”. There was no depressant action of any importance 
and no toxic action on the kidneys. 
Tetrachlorethylene is now in fairly extensive use in industry, but so far no 
reports of the effect on workers, who are exposed to the fumes, has been published. 
Ethylene dichloride, sometimes called ethylene chloride but which really is 
dichlorethane, has come into prominence recently as an excellent solvent and a 
dangerous poison. It is used in the separation of wax from petroleum, in oil 
extraction, in dry cleaning, in the production of photographic films and as a 
thinner in lacquers, especially for coating the interior of beer vats. The last was 
the source of 2 severe cases reported to one of us (A.H.) by State inspectors. In 
1937 von Oettingen240 could find no industrial case reported in the literature, but 
two years later Wirtschafter and Schwarz344 saw 3 cases in men, who used this 
solvent for cleaning yarn, working over an open vat in a hot room (750 F.), lift- 
ing out the yarn and wringing it by hand. The effect was characteristic of a 
narcotic poison, but, in addition, there were severe dermatitis of the hands, leuko- 
cytosis of 12,400 to 18,250 and liver disturbance, as shown by extremely low blood 
sugar levels, but no evidence of kidney involvement. Recovery followed removal 
from the fumes and treatment with calcium and a high carbohydrate diet. They 
conclude that it is less toxic than CC14. 
Sayers and his colleagues272 tested ethylene dichloride on animals and found 
that inhalation of air containing 1 per cent, for 20 minutes caused the animals, 
after a day or two, to die with congestion and edema of the lungs and secondary 
degenerative changes in the kidneys. The narcotic action is about equal to that 
of CHC13 and CC14, but there are less serious sequelae. 
McNally and Fostnedt214 report 2 cases of chronic poisoning in men who 
had been exposed, one for 2 months and the other for 5 months, to the vapors of 
ethylene dichloride (dichlorethane). The symptoms consisted in anorexia, 
nausea, vomiting, epigastric distress, drowsiness, tremors and nystagmus. 
Tetrachlorethane is, by common consent, the most toxic of the chlorinated 
hydrocarbons that have been used in industry. Penta may be more so, but we 
know little about it. It came into prominence during World War I, when the 
wings of war planes were covered with a dope of cellulose acetate, and tetra- 
chlorethane is its best solvent. The Germans had discovered its dangerous nature 
before the war broke out, for there had been in airplane plants a number of cases 
of acute yellow atrophy of the liver, and the pharmacologists, Grimm, Heffter and 
Joachimoglu104, had identified this constituent as the one responsible, but none 
Vol. IV. 944 644 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
of that information reached England, and the English had to go through the same 
experience, toxic jaundice in airplane dopers, the cause to be discovered by Will- 
cox333, and a resultant discontinuance of its use. We were warned in time by the 
English and escaped that particular danger. The first reported case in American 
industry came from the manufacture of acetate rayon, but the solvent is used no 
longer in that industry. 
For many years we heard nothing about this solvent beyond occasional rumors 
that it was being used in coatings, in laundry “ mix ” and in non-inflammable film 
production, but no cases of poisoning were reported. Now, however, we are told 
that it is coming back into use, a fact to be deplored, if true, for it is highly toxic, 
although fortunately its volatility is low; it is six times as heavy as air. 
Characteristically tetrachlorethane is absorbed slowly and its action is pro- 
longed. One does not read reports of acute narcosis but rather of vague symp- 
toms, nervous and digestive, which slowly progress to serious illness. The form 
most often described is acute yellow atrophy of the liver, which appears in British 
factory inspection reports under the head of toxic jaundice, along with arsine 
poisoning. The immediate cause of death in both these classes may be hem- 
orrhage from stomach or intestines or from the nose. Finally, the Germans report 
cases with a predominance of nervous symptoms and no apparent injury to the 
liver (Brezina and Teleky22). 
Minot and Smith223 were able to detect in men and women exposed to mild 
concentrations a characteristic change in the leucocytes which may serve as a 
warning that absorption and damage are taking place. This is the appearance of a 
relatively large number of leucocytes of the endothelial type, which may run as 
high as 40 per cent., the cells showing degenerative changes more and more as 
their number increases. 
Penta- and hexa-chlorethane are coming into industrial use. Hexa is said to 
be a constituent of a secret explosive. Theoretically they should behave much as 
does tetrachlorethane, but we have as yet no data concerning them. 
Methyl chloride or monochlormethane is used very extensively as a refriger- 
ant, and most of the instances of intoxication, whose histories have been published, 
have been caused by the escape of fumes into dwellings; only a minority were 
of industrial origin, in makers or repairers of refrigerators. Most of the cases 
of industrial intoxication, which have come to light, are the result not of acute 
narcosis but of repeated exposures to small doses, which gradually cause injury 
to the central nervous system. The earliest industrial cases were characterized by 
increasing fatigue, lassitude, anorexia, muscular weakness and finally, somnolence 
and dimness of vision. To this picture nausea, vomiting, restlessness and insom- 
nia sometimes were added, also ptosis, fine tremors and staggering gait. Baker93 
found formic acid in the urine. No fatality from the industrial use of methyl- 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
645 
chloride has been reported, unless one accepts a case, described by Schwarz279, in a 
man who was very nervous for three weeks after an acute poisoning, and then 
lost consciousness and died in convulsions. From the animal experiments of 
Sayers and his colleagues273 and from the autopsies on the victims of the mass 
poisoning in Chicago in 1929 (Kegel and associates159) it is evident that methyl- 
chloride causes an acute nephritis with degenerative changes in liver and spleen, 
hemorrhages in lungs, intestinal tract and dura, and, in the Chicago cases, primary 
anemia with leucocytosis. Of those that survived in that epidemic a number had 
some sequelae, usually of a character to indicate degenerative changes in the cen- 
tral nervous system. 
The most recent case in the literature comes from England. In 1940 Chalmers 
and associates38 examined a refrigerating engineer, who was acutely intoxicated 
by methylchloride, with delirium, convulsions and tremors. They found large 
quantities of coproporphyrin, series III, in urine and feces, disappearing with the 
disappearance of the toxic symptoms. Recovery was not complete till the end 
of the seventh week. 
A. M. Jones157 reports 7 English cases, but only one was severe, the first one 
of that character to be reported in that country. The men were refrigerator re- 
pairers and, since the gas is not disagreeable, all had inhaled it in the course of 
their work in sufficient quantity to cause headache, dizziness, staggering gait, 
followed some hours later by nausea and vomiting. Loss of appetite was common. 
However, the men were not incapacitated, and the only observed sequelae were 
attacks of depression and vomiting. Eye symptoms were common, misty vision 
and diplopia. In the severe case there was involvement of the central nervous 
system and hepatic and renal damage and depression of marrow activity. 
There has been a great increase in the use of methyl chloride for refrigeration 
since the present war began and for air conditioning in the place of freon, dichlor- 
odifluoromethane, which now is largely preempted for use as a disperser of insecti- 
cides. Engineers warn that methyl chloride is inflammable and explosive as well 
as toxic. 
Ethylene chlorhydrin is reported to have caused 2 deaths in German industry 
(Koelsch169) and 2 severe cases, one fatal, in English (Middleton219). It is a by- 
product in the making of synthetic indigo and is a good solvent for fats. The 
action is that of a narcotic poison with characteristic lesions in liver, spleen 
and lungs. 
Chlorinated naphthalenes. — These very valuable insulating waxes are com- 
pounds of naphthalene with a chlorine content which runs from about 20 to 65 
per cent. The products of higher chlorination came into use later than the lower 
ones. In this country they are known as halowax, and this wax has been a notori- 
ous source of acne, “ cable rash ” or “ blackhead itch ” often of a severe type 
Vol. IV. 944 646 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
(Mayers and Silverberg205, Sulzberger, Rosenberg and Scher305 and Schwarz282). 
The Germans described it under the name of “ chloracne ” caused by “ perna 
a mixture of these compounds310. 
For some twenty years halowax was used in electrical insulation without any 
more serious injury to the users than skin lesions, but when the higher members 
of the group, penta and hexa, came into use, cases of fatal jaundice, acute yellow 
atrophy of the liver, began to appear, few and scattered, but fortunately in States 
where such cases are investigated carefully. In 1936 3 fatal cases were recog- 
nized as linked up with exposure to fumes of halowax, either melted or dissolved 
in carbon tetrachloride and ethylene dichloride. The industrial hygiene bureaus 
of New York, Connecticut and Massachusetts were unable to get any history of 
similar cases among users of chlornaphthalenes in foreign countries. But in 1938 
the Annual Report of the Chief Inspector of Factories for Great Britain made a 
brief statement about 3 fatal cases of toxic jaundice which were traced to inhala- 
tion of fumes of chlornaphthalene. 
The 3 original cases are summarized in a paper by Flinn and Jarvik77, 
who also succeeded in producing fatal liver lesions in animals by injections of 
chlornaphthalenes from tri up to hexa. The histories of these cases are given in 
full by Greenburg and associates in The Industrial Bulletin, State of New York, 
18, No. 40, 1939. At this time the purveyors of halowax, the Halowax Corpora- 
tion, asked C. K. Drinker and his colleagues55 of the Harvard School of Public 
Health to make a thorough study of the problem. These investigators succeeded 
in producing severe lesions in the liver by means of penta- and hexa-chlornaph- 
thalene, the more readily when the action of CC14 was added to that of the chlor- 
naphthalenes. With tri and tetra the lesions were much less serious. Drinker 
adds to the first 3 human cases 4 non-fatal ones. It is interesting to note that 
in their animal experiments he and his colleagues found that rats, which had shown 
no clinical evidence of disease from the chlornaphthalenes, would die promptly, 
if they were given a small dose of CC14. Lesions always were confined to the liver. 
In 1942 Mayers and Smith206 reported the history of a non-fatal case of toxic 
jaundice in an 18-year-old girl, who had breathed fumes of chlornaphthalenes, 
which were given off when she used a soldering iron on condensers impregnated 
with chlornaphthalene wax. The first symptom noted in this case was edema, 
which appeared before the icteroid tinges in the sclera. Later there was jaundice 
with anorexia, nausea and severe abdominal pains, but edema was the outstand- 
ing feature. The authors hold that the edema was produced by hypoproteinemia 
caused by the liver damage (serum albumin 1.7 gm. per 100 c.c., serum globulin 
2.5 gm. per cent.) and that it can be controlled by increasing the blood protein. 
Up to 1942 the only published histories of this form of poisoning were all of 
American origin, but in that year the first English case was described in detail 
Vol. IV. 944 ALIPHATIC OR PETROLEUM SERIES OF SOLVENTS 
647 
by McLetchie and Robertson212, a case of toxic jaundice in a woman who for 
six months was exposed to chlornaphthalenes. Some of her fellow workers had 
the usual acneiform eruptions, but there was no other case of jaundice. The 
illness came on slowly, jaundice appeared and increased, the patient passed into 
coma and died in the fifth week. 
Just recently Greenburg" has reported an outbreak of toxic jaundice in two 
factories in New York State producing insulated wire and other electrical appara- 
tus. In one of them 2 fatal cases of acute liver disease occurred in the spring 
of 1942; in the other there were at least 4 fatal cases during the year and several 
of systemic poisoning requiring hospital care as well as many cases of acne. 
Drinker’s studies55 show that the allowable concentration for the lower mem- 
bers of the group, such as trichlornaphthalene, is 10 mgm. per cubic meter of air, 
but for the higher members, such as penta and hexa, it should not go over. 0.5 
mgm. They also warn against the use of carbon tetrachloride as a solvent, for 
that greatly increases the danger. Preventive measures should be based on the 
fact that the vapors are much heavier than is air. The examining physician should 
be careful to reject men, who might already have liver damage, e.g., syphilitics 
under arsphenamine treatment. Greenburg warns against allowing a worker, who 
shows any evidence of even mild liver damage, to go back to work, for the result 
may be fatal. 
Another source of “ chloracne ” has come to light lately, cutting oils to which 
organic chlorine compounds have been added. The mists from such oils used in 
heavy cutting and grinding operations cause skin lesions like those of “ cable 
itch ” 
Bromine Compounds of the Hydrocarbons 
These are less narcotic but much more toxic than the chlor compounds. For- 
tunately they are far less useful in industry. Methyl bromide, ethyl bromide 
and ethylene dibromide have been used as refrigerants, especially abroad. Sayers 
and Yant273 tested these compounds on animals and found methyl bromide much 
the most toxic. The known cases of poisoning by bromine derivatives, usually 
methyl bromide, come to us from foreign reports, German and Swiss chiefly. Even 
in those countries they are rarities. 
Methyl bromide has come into extensive use in this country as a fumigant for 
foods, to get rid of insects. It is shipped as a liquid in cylinders and either allowed 
to evaporate directly into the fumigation area or conveyed there by pipes. Al- 
though it has been used thus for some years and on a large scale, no reports have 
reached us of harmful results. One of the very rare cases of industrial methyl 
bromide poisoning in this country was reported to one of us (A.H.) in 1926. This 
was in a man, who inhaled the gas while charging a refrigerator, made no com- 
Vol. IV. 944 648 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
plaint at the time, was seen to stagger home two hours later and fell unconscious 
at his door. He had a series of convulsions suggesting uremia, and catheteriza- 
tion showed the bladder to be empty. He died nine hours after his exposure. 
Methyl bromide poisoning has several unique characteristics; a definite latent 
period, a profound action on the motor system with violent jerkings or clonic 
convulsions, visual disturbance from retinal hemorrhage, fever, delirium, coma 
and after death, a complete disappearance of the poison from the tissues and 
fluids of the body (Irish and associates150). Victims who survive show evidences 
of profound injury to the nervous system. 
Recently Watrous325 has published his observations on 90 men exposed to low 
concentrations of methyl bromide, less than 35 parts per million. He found symp- 
toms of mild intoxication in 33, skin lesions in 22. Watrous warns that organic 
matter such as rubber and adhesive tape may retain methyl bromide a long time. 
The action of ethyl bromide is chiefly on the kidney, and a diffuse acute paren- 
chymatous nephritis is the most prominent change found in animals dying from 
exposure to the fumes. For ethylene dibromide see Thomas and Yant315. 
Aromatic or Benzene Series of Solvents 
Coal Tar Benzene or Benzol 
Coal tar benzene or benzol is the most dangerous of the industrial solvents 
with the exception of tetrachlorethane. It is so recognized in industry, and its use 
has been abandoned, often at a good deal of sacrifice, by conscientious employers, 
who refuse to subject their workers to such a risk. Many, however, have been 
obliged to go back to its use now, since toluene cannot be secured because it is 
needed for trinitrotoluene. 
Benzene was brought to the attention of the medical world first in 1897, when 
Santesson-71, a Swedish toxicologist, read a paper before the International Medical 
Congress in Moscow, in which he described 9 cases of hemorrhage under the skin 
and from mucous membranes in girls using benzene rubber cement in a tire fac- 
tory, 4 of these cases ending in death. Then 13 years later Selling286 of Johns 
Hopkins reported 3 similar cases in girls using a benzol rubber seal for tin cans. 
Selling made many experiments on animals and established the basic facts under- 
lying the pathology of benzene poisoning, namely, that it acts chiefly on the 
blood forming tissues, the marrow of the long bones and the lymphatic structures, 
producing anemia and granulocytopenia together with a loss of the clot forming 
substances in the blood. 
The clinical picture that emerges from these early studies is one of progressive 
weakness, dizziness, headache and vomiting, then the appearance of purpuric 
spots on the skin, bleeding from gums, throat, nose and uterus and in fatal cases, 
Vol. IV. 944 AROMATIC OR BENZENE SERIES OF SOLVENTS 
649 
death from severe hemorrhage or toxemia. 
Selling’s work in the experimental field was confirmed by many students, who 
found that in animals the most important effect is leucopenia; the fall in the red 
cell count is far less striking; the most important change found postmortem is 
aplasia of the bone marrow; damage to the lymphadenoid tissues is far less impor- 
tant. Among the leucocytes the polynuclears suffer the most. In the early stage 
of poisoning stimulation of cell production is seen in the marrow accompanying 
the destructive process. Regeneration can occur after an advanced degree of 
aplasia. Benzene also is a direct leucotoxic poison acting on the white cells of the 
circulating blood. 
Other features were added to Selling’s findings. Duke00 found in rabbits a 
rapid rise in the platelet count followed by a rapid fall, while the bone marrow 
showed almost complete absence of megacaryocytes. Animal experiments also 
showed the effect of benzene on the formation of antigen. Rusk269 found a reduc- 
tion in the formation of lysin for sheep’s blood and of precipitin; Simonds and 
Jones292, a loss of hemolytic and agglutinating substances; Hektoen135, a loss of 
lysin and precipitin; Winternitz and Hirschfelder342, reduced resistance to pneu- 
mococci; White and Gammon328, to tubercle bacilli. Camp and Baumgartner31 
found that benzolized animals failed to have a normal reaction to injuries pro- 
duced by heat, chemical irritants and unsterilized foreign bodies, i.e., no leuco- 
cytosis and no increase of leucocytes in the injured area. 
Those years produced more careful experimental work with benzene than 
clinical studies, and because of this a standard for diagnosis emerged which was 
based on animal response, not on human. 
It is a serious error to assume that all the observations made on animals are 
true of human beings with benzene poisoning, for there are marked differences. 
Thus Hurwitz and Drinker147 found only slight signs of hemorrhage in their 
experimental rabbits and, as a rule, no prolonged bleeding time. Even more im- 
portant is the difference in the degree of anemia. In animals leucopenia is far 
more striking than anemia, and it was assumed for many years that that was true 
also of benzene poisoning in working people; therefore that the earliest and most 
trustworthy sign was a fall in the white cell count, below 5,000, a red cell count 
being unnecessary. Many early cases must have been missed under this mistaken 
procedure, for in man the loss of red cells may be greater than the loss of white 
cells and it may appear earlier. 
Acute benzene poisoning is of little importance under modern industrial man- 
agement. The danger is well understood, and no longer are men sent unprotected 
into tank cars or vats. It is a narcotic poison, which acts with great swiftness 
producing unconsciousness or helpless confusion. In such cases it is often the 
rescuer, exerting himself to save the victim, who gets a fatal dose, while the 
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INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
passive victim survives. As a usual thing recovery in non-fatal cases is complete 
with no sequelae. 
Chronic poisoning is far more important. It comes on slowly, the symptoms 
are vague, and often it is not till the stage of hemorrhage has been reached that 
the victim seeks help. The bleeding may be from the nose, the gums, the uterus, 
into the subcutaneous tissue, more rarely into the retina or stomach or intestines. 
An examination of the blood at this stage shows marked changes, an anemia of 
the non-regenerative type, a granulocytopenia, prolonged bleeding time and de- 
layed clotting. In such cases the diagnosis is easy, if benzene exposure has taken 
place. The process may be halted under appropriate treatment, or it may pro- 
gress even to a fatal ending without any further exposure. This fact is stressed 
by Selling and Osgood and a number of such instances are to be found in the 
literature (Rohner and Baldridge266, Andersen2). 
For the physician the most important task is to detect benzene poisoning in 
the early stage before serious damage has been done. Blood and urine examina- 
tions should serve to reveal this stage. 
Theoretically there should be a stage of marrow stimulation with high blood 
cell counts and immature forms, and actually this stage has been observed. Teleky 
and Weiner311 found in the blood of women benzene workers nucleated red cells, 
anisocytosis and poikilocytosis. Ross-Smith294 found a high red cell count, over 
5 million, in 14 out of 71 women, also an increase in large epithelioid cells. 
As for the diagnosis of benzene poisoning in the very early stage opinion has 
changed very decidedly in recent years. As the study of benzene poisoning in 
man has proceeded, the simple picture formerly established has had to be aban- 
doned and the fact accepted that benzene is a bone marrow poison, whose action 
may be exerted now on one element of the marrow, now on another. There may 
be polycythemia or anemia, leucocytosis (polynuclear or lymphatic) or leuco- 
penia, there may be a complete absence of youthful forms or abnormal forms, 
there may be reticulocytes, myelocytes, anisocytosis and poikilocytosis, eosino- 
philia, megalocytosis. The color index may be low, normal or high. Benzene is a 
bone marrow poison, but the attack may be now on one element, now on another; 
indeed there is evidence to show that a stimulation of one may go on at the same 
time as destruction of other elements118,278. 
Donald Hunter145 saw an illustrative case in a young girl, who was exposed 
for 4 years to fumes from a mixture of 7 per cent, benzene with Russian benzine, 
which contains a fairly high percentage of benzene. On her first examination 
she was clinically well except for purpura of the limbs and a past history of menor- 
rhagia. The first blood count showed a reduction only of platelets, 51,000, and 
of polynuclear leucocytes, 40 per cent., but the red count was 5,100,000, the white, 
7,600. However, only 48 hours later she had severe bleeding from the gums, 
Vol. IV. 944 AROMATIC OR BENZENE SERIES OF SOLVENTS 
651 
lungs and gastrointestinal tract. The platelets disappeared from the circulating 
blood, the red cells fell to 1,000,000, but the white cells rose to 15,000. _ Under a 
mistaken diagnosis splenectomy was performed, and the peritoneal cavity was 
found full of blood. She survived the operation and slowly recovered, the plate- 
lets reappeared, 132,000, in the second week, the red cell count rose to 3,300,000, 
white cells were 8,200 with polynuclears 41.5 per cent. Another English report 
by Hamilton-Paterson121 in 1941 confirms these findings. The author describes 
3 cases of poisoning, one fatal, and also the blood changes in 18 other women 
exposed to benzene. The blood picture varied greatly, anemia, polycythemia, 
leucopenia, leucocytosis, relative decrease, relative increase of polymorphonuclears 
and eosinophiles. 
Andersen’s2 case is a contribution to the literature of atypical benzene poison- 
ing. Here there were several interesting features. The disease developed about 
5 months after exposure, and continued to progress for 18 months after ex- 
posure had ceased; death was caused by general septicemia, streptococcus 
hemolyticus; the red blood cells showed marked variations in size and shape with 
polychromatophilia and basophilic stippling. Two normoblasts were seen. The 
polymorphonuclear cells were young, showing a marked shift to the left. A few 
weeks before death the reticulocytes made up 12.3 per cent., normoblasts 10 per 
cent., and there were monocytes, myelocytes and myeloblasts. Autopsy revealed 
hyperplasia of the marrow and acute splenic tumor. 
A recently discovered aid in the diagnosis of early benzene poisoning is the 
urinary test devised by Schrenk, Yant and Sayers276 of the Bureau of Mines. 
They found uniformly in a series of about 100 animals an early sign of benzene 
poisoning in the urine, namely, a decrease in the proportion of inorganic sulphates 
to total sulphates, this decrease being marked in accordance with the severity of 
the intoxication. The same decrease was found in benzene workers. 
Normally the inorganic sulphates make up 85 to 95 per cent., the organic, 
ethereal or conjugated, 5 to 15 per cent., but in cases of benzene absorption the 
phenolic products that are formed take up the sulphur, and the result is an increase 
in the conjugated sulphates which reverses the above proportions. “ The most 
important fact relating to this test is that the decrease occurs rapidly on exposure 
to benzol and well in advance of leucopenia or anemia or other evidence of 
damage ”276. 
In other hands this test has proved of minor value. The studies made by the 
Boston and New York groups18 showed that it failed in some cases of clinical 
poisoning and could not be depended on to reveal absorption of benzene. Like 
conclusions were made by the Public Health Service. 
Vigliani251, who has seen many cases of benzene poisoning in Italian rubber 
works, divides them into four classes: (i) those clinically, hematologically and 
Vol. IV. 944 652 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
anatomopathologically typical of aplastic anemia; (2) those clinically typical of 
aplastic anemia but showing an active hemopoiesis especially in the bone marrow, 
pseudo-aplastic anemia; (3) those with a typical aplastic anemia with myelitic 
hyperplasia or metaplasia resembling leucemia especially in liver and spleen; 
(4) those with chronic or acute leucemia, not infrequently appearing as aleu- 
cemia. All these forms have been demonstrated experimentally in animals. 
As to the fourth class, evidence is piling up that leucemia, myeloid or lym- 
phatic, may be one of the forms benzene poisoning may take. Vigliani and Penati 
collected 10 cases, which had been reported by 1938, and Mallory and his col- 
leagues have added 2. 
It may be well to give a brief summary of the newer additions to our knowl- 
edge of this form of industrial poisoning, which we owe to the studies made by a 
group in New York (Division of Industrial Hygiene, State Department of Labor 
and Hospital of the Rockefeller Institute) and a group in Boston (Division of 
Occupational Hygiene, State Department of Labor and Massachusetts General 
Hospital18). 
(1) The diagnosis of benzene poisoning, mild or severe, must be made on the 
whole blood picture, and the earliest and most frequent deviation from the normal 
consists in a fall in the red cell count and an increase in the mean corpuscular 
volume of the red cells. A fall in platelet count and a reduction of hemoglobin 
follow in frequency, but a fall in the white cell count is less characteristic of early 
poisoning than any of the above. Anemia and macrocytosis are the changes to 
be looked for. 
(2) Increase of urobilinogen and deviation from the normal urine sulphate 
partitions were not found to be of value in diagnosis. 
(3) Bleeding time and coagulation time were of no aid, being prolonged only 
in severe cases. 
(4) Clinical symptoms, weakness, fatigue, epistaxis, dryness of the throat, 
anorexia, nausea, dizziness, insomnia, were of dubious value, because, although 
they were present in workers exposed to benzene more than in controls, they were 
absent in some cases of serious poisoning. 
(5) Purpura, particularly bleeding from the mucous membranes, was rela- 
tively rare, being absent in some severe cases. 
(6) In severe poisoning the blood may show changes like those in pernicious 
anemia. Erf and Rhoades18 noted a feature of benzene intoxication, which may 
prove helpful in distinguishing it from pernicious anemia, namely, that free 
hydrochloric acid is present in the gastric juice. 
(7) An aplastic marrow is not typical of benzene poisoning; hyperplasia 
may be found even more often. In 16 cases, 12 men and 4 women, the 4 women 
all showed aplasia, but only 2 of the 12 men; the other 10 showed hyperplasia. 
Vol. IV. 944 AROMATIC OR BENZENE SERIES OF SOLVENTS 
653 
This seems to point to a tendency of the male to react with hyperplasia, of the 
female with aplasia and suggests that the belief that women are more susceptible 
to benzene than men may be based on the failure hitherto to recognize the hyper- 
plastic form of the disease. 
(8) A study of the hyperplastic cases reveals what may be called a neoplastic 
tendency, rapid growth as shown by mitotic figures, the development of cells hav- 
ing no counterpart in normal tissues but common to a variety of malignant tumors. 
In a case seen by one of us (R.G.J.) the marrow was full of mitotic figures, and 
there were occasional giant cells with monstrous nuclei, suggesting a neoplastic 
tendency. A close similarity between these hyperplastic marrows and those de- 
scribed by Martland202 in chronic radium poisoning was noted, and in both cases 
there is a prolonged latency and a tendency to progress for months or years after 
exposure has ceased. 
The influence of benzene on the course of infections in animals has been 
reviewed. Clinical cases confirm these facts. Thus Rohner and his colleagues266 
noted as an outstanding feature the decided lack of response on the part of their 
patient to infection. Of Hunter’s18 first 4 cases, those that died had septic tem- 
peratures, as did Selling’s first case, but the 2 that recovered did not. Meda216 
reported a case of prolonged suppurative cysto-pyelonephritis; Smith294 reported 
one of obstinate suppuration of the axillary lymph nodes, another of abscess in 
the thigh. Severe lesions of the mouth are the most frequent manifestation of 
this action of benzene, and Vincent’s angina was noted in several cases. Mart- 
land (see reference no. 118) saw osteomyelitis of the lower jaw and gangrenous 
stomatitis. Loewy’s192 case was one of death from gangrenous osteomyelitis of 
the jaw and gangrene of the lungs. 
It is probably true of working people poisoned by benzene, as it was of the 
early cases of radium poisoning, that a diagnosis of Vincent’s angina or osteo- 
myelitis was made in many cases without inquiry into a possible occupational 
cause. 
The use of benzene has increased not only because of the demand for toluene 
for explosive production, but because the new method of distilling petroleum at 
a great heat, “ cracking ”#, results in a gasoline or naphtha containing coal tar 
bodies, benzene among them, sometimes in a high proportion. The manufacturer 
may believe he is using a safe solvent free from benzene, when actually there 
is a dangerous amount of benzene present. 
The American Standards Association has pronounced ioo parts per million 
to be the maximum allowable concentration of benzene. 
# Cracking petroleum means heating it above its decomposition point in order to “ crack ” 
or break up the large molecules of the heavy hydrocarbons to form smaller molecules of the 
lighter. Aromatic compounds begin to appear at 8oo° F. and at i,ooo° F. the amount is 
appreciable. 
Vol. IV. 944 654 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Toluene (Toluol): Methyl Benzene and Xylene (Xylol): Dimethyl Benzene 
The textbooks say that toluene is a stronger narcotic than benzene, but that 
is based on animal experiments with measured quantities of vapor. In practical 
life the greater volatility of benzene makes the danger of narcosis much greater 
than with toluene or the still heavier xylene. In fact it is very rare to hear of a 
case of acute toluene poisoning of any severity, still rarer of xylene poisoning. 
As for chronic poisoning Batchelor (see ref. 341) of the Public Health Service 
tested toluene, xylene and that mixture of higher homologues called solvent naph- 
tha or hi-flash naphtha and failed to produce in any of the animals the severe ane- 
mia and leucopenia of benzene poisoning; nor did Winternitz342 find a loss of de- 
fensive bodies in the blood. In Selling’s286 experiments with toluene there was 
destruction of leucocytes but far less than with benzene, and it was compensated 
rapidly. Hektoen135b found no marked changes in the bone marrow or in the 
absolute or relative white count. 
According to Cushny47 toluene is oxidized in the body to benzoic acid and then, 
combined with the glycocol of the body, it is excreted as hippuric acid. Benzene 
is oxidized to phenol and dioxybenzol, which combine in the kidney with sulphuric 
and glycuronic acids to form conjugate acids and the corresponding dioxy com- 
pounds. 
Nevertheless from all the industrial countries, Germany especially, come con- 
tradictory reports concerning the two methyl derivatives of benzene, some assert- 
ing the safe character of these solvents, others the contrary. Reports, have 
appeared from England and from Germany with claims that toluene and xylene 
have been proved to exert an action on the blood forming tissues which differs not 
at all from that of benzene. Most of the German cases were in printing establish- 
ments, probably in rotogravure work, where large quantities of xylene or xylene 
and toluene seem to be used302’236. For instance, there is the case of a lithographer, 
who was exposed for a long period to xylene fumes, and died of aplastic anemia. 
The autopsy showed severe damage to the bone marrow, atrophy of lymphoid 
tissue and complete atrophy of the normal cellular elements in spleen and lymph 
nodes. There were also 12 cases of poisoning in German color printers, who 
showed leucopenia and thrombopenia but in only 2 cases a reduction in red cells. 
Here, however, benzene was used in addition to the other two. Gerbis, who has 
had a long experience in the German factory inspection service, says that the 
cases in the printing industry are severe in proportion to the amount of benzene 
present in the solvent, and that toluene and xylene are far less harmful. One of 
the recent series of experiments on blood changes from these two homologues 
was reported by Engelhard^7, who found a decrease in the number of red cells 
after exposure to high concentrations, a proportionately lowered hemoglobin, a 
Vol. IV. 944 AROMATIC OR BENZENE SERIES OF SOLVENTS 
655 
marked leucocytosis and a considerable fluctuation in the proportion of lympho- 
cytes to polynuclears. These are, of course, far less severe changes than those 
caused by benzene. So far Ferguson and his colleagues74 are the only ones who 
insist that toluene and benzene have an identical effect on the blood. They tested 
the two on rabbits and rats and found that, while benzene is the more toxic, prob- 
ably because of its greater volatility, the effects of the two on the blood forming 
organs are similar, first stimulating the formation of young blood cells, then 
producing leucopenia, anemia and thrombopenia. They also describe a case of 
agranulocytic anemia in a workman exposed to toluene (see also R. H. Wilson340). 
Smyth and Smyth297 observed in experimental toluene poisoning signs of early 
toxic damage in the cells of liver and kidney and some pulmonary inflammation 
but only after inhalation of heavy fumes. 
The authors of this chapter have had confidential communications from sev- 
eral industrial physicians who have had disappointing results following a change 
from benzene to toluene. Instead of a disappearance of the leucopenia and 
anemia there was little if any change in the blood, in one instance even after the 
lapse of 3 years. In fact not only did the low counts persist, but some women, 
whose blood counts had been normal at the time benzene was discontinued, devel- 
oped polynuclear leucopenia and low red cell count and low hemoglobin while 
working with toluene. This is a puzzling situation. One does not know whether 
to assume a persisting action of benzene even after exposure has ceased or a 
combined action, the toluene continuing the damage begun by the benzene. A 
striking instance of this is a case of fatal aplastic anemia reported to one of 
us (A.H.). 
A leather worker was exposed to benzene continuously from 1918 to 1928 
and thereafter was exposed to a substantial quantity of toluene vapors from 1928 
to 1931, when he was disabled and six months later died of aplastic anemia with 
typical blood changes. The autopsy was performed by Martland, who found an 
aplastic marrow, and the award was rendered in favor of the widow and depend- 
ents on the ground that exposure to toluene can produce chronic poisoning or 
aggravate a benzene poisoning previously acquired. 
A number of mass observations of workers exposed to toluene have been 
made in recent years. Greenburg and his colleagues103 examined 106 painters and 
a control group of 430 fur workers. The concentration of toluene in the work- 
rooms ran from 100 to 1,100 parts per million. Sixty-one painters had had no 
exposure to other solvents; 45 had had exposure to other solvents, 30 of them 
to benzene. The comparison with the controls ran as follows; enlarged liver, 
painters 30 per cent., controls 7 per cent.; in the 61 with no previous exposure, 
only 21.4 per cent, had enlarged liver, but even this is three times the control 
rate. There was in the painters’ group a slight decrease in the red cell count and 
Vol. IV. 944 656 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
a slight lymphocytosis; the mean corpuscular volume was somewhat increased in 
23.6 per cent, (controls 7.2 per cent.); the hemoglobin was higher; values of 16 
gm. per 100 or more were found in 37.7 per cent, as contrasted to 2.4 per cent, 
of the controls. All these deviations from the normal were slightly more marked 
in men who had had previous exposure to benzene. 
The Public Health Service243 tested concentrations of toluene from 50 to 800 
ppm (parts per million) on three normal subjects and concluded that inhalation of 
200 ppm for 8 hours causes slight but definite impairment of coordination and 
reaction time, which is liable to increase the danger of accidents; with higher con- 
centrations these effects increased and at 600 to 800 ppm they could be observed 
after a few hours’ exposure. The elimination of hippuric acid in the urine in- 
creases with the concentration of toluene in the air, but the ratio of inorganic to 
organic sulphates is not affected by toluene, nor was there any sign of injury to 
the blood forming organs. 
The latest study of toluene exposure in a large group is that of Rex H. Wil- 
son340, who was able to follow the history of some thousand employees working 
with commercial toluene for one to three weeks in concentrations from 50 to 1,500 
ppm. One hundred showed symptoms severe enough to send them to the hospital 
for examination, and to of these showed blood changes. There were no deaths. 
Those exposed to concentrations no higher than 200 ppm. were practically unaf- 
fected; at 200 to 500 ppm headache was complained of, and there developed 
nausea, anorexia, bad taste in the mouth, lassitude, slight but definite impairment 
of coordination and reaction time, but no significant physical or laboratory find- 
ings were noted. When the concentration of toluene was over 500 ppm, all the 
above disorders were increased, sometimes markedly, and in several cases petechial 
hemorrhages appeared under the skin. 
In most of the cases the blood picture was normal except for a fall in the red 
cell count, usually down to 2,500,000. Leucopenia was found in only 2 cases, 
with white cell counts 2,500 to 3,000; here all the other blood elements were re- 
duced, and biopsy of the bone marrow disclosed partial destruction of the blood 
forming elements. 
In dealing with commercial toluene and xylene, it must never be forgotten 
that both are very likely to contain benzene. The ordinary method of distilling 
these bodies does not make for their complete separation, nor is it necessary in 
industrial use to have pure products. 
The maximum allowable concentration for toluene has been set by the Ameri- 
can Standards Association at 200 ppm (parts per million), for xylene at 200 ppm. 
Vol. IV. g44 AROMATIC OR BENZENE SERIES OF SOLVENTS 
657 
Benzene Derivatives 
The derivatives of the benzene ring are numerous; they are industrially im- 
portant, and they are of course extremely complex. New ones are introduced 
continually, too rapidly to allow the toxicologist to keep pace with the chemists, 
who produce them, and as a result we have here a most obscure and difficult field 
for the industrial physician. Sometimes it is possible to predict from the chem- 
ical composition of the simpler members of the coal tar group what the physio- 
logical action probably will be, although even here the problem of the isomers 
enters, for of three compounds with the same formula the one in the para posi- 
tion may differ in its action from the one in the ortho position and both from the 
one in the meta position. Thus the toluidins are toxic in this order; para first, 
then ortho, then meta. The French high explosive, melinite, is a mixture of tri- 
nitrophenol and of the isomer of dinitrophenol which has the two NO, groups 
and the HO group attached to the ring in the 1-2-4 position. This isomer proved 
during World War I to be highly toxic with a characteristic action which was not 
shared by any of the others. Later on, its use as an anti-obesity drug amply con- 
firmed the French observations. There is also a decided difference in the toxicity 
of substitution products formed by displacement of the hydrogen in the ring and 
those formed by displacement of hydrogen in a side chain. An example of the 
former is toluidin, which is very toxic, of the latter, benzylamine, which has the 
same written formula but is fairly harmless. Many other illustrations could be 
given, but these are sufficient to indicate some of the complexities of the subject. 
According to Fraenkel81 the entrance of the HO nucleus to form the phenols, 
naphthols and cresols increases toxicity, but industrially these bodies give very 
little trouble except in the matter of burns with a very rare case of extensive skin 
absorption followed by collapse and death. The entrance of chlorine into an 
aliphatic compound increases its toxicity, but the reverse is true of an aromatic 
compound. The chlorbenzenes are less toxic than benzene. The nitroso group 
and the nitro group always increase toxicity, but when a nitro compound is re- 
duced to an amino, as when nitrobenzene is reduced to aniline, the toxic charac- 
teristics remain much the same, but the intensity of action is lessened. 
Aniline: Nitrobenzenes: Nitrotoluenes 
According to some authorities all of the clinical manifestations of poisoning 
by the nitro and amino benzene derivatives may be explained by the formation of 
methemoglobin and the resulting oxygen starvation, but in very rapid and severe 
poisoning a direct action on the central nervous system takes place before methem- 
oglobin is formed (Heubner137). Clark, van Loon and Morrisey42 testing ani- 
Vol. IV. 944 658 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
mals with aniline decided that the most important action is the formation of 
methemoglobin, with resulting anoxemia and depressant action on the central 
nervous system which is specially sensitive to anoxemia. With this Young and 
his colleagues351 agree but add a direct toxic action as shown by a marked fall in 
blood pressure and cardiac arrhythmia. 
The effect on the bone marrow is at first to stimulate active red cell produc- 
tion as shown by polycythemia, although sometimes with low color index, and 
then inactivity follows. There are evidences of effort at regeneration, stippled 
red cells, polychromatophilia, nucleated forms, variation in size and diminished 
platelets. An early leucocytosis is followed by a lymphocytosis. The blood often 
is chocolate-colored and appears thicker than normal. It may be impossible to 
make hemoglobin estimations by means of color scales, for the methemoglobin 
changes the color of the blood. 
The smoky or dark brown or port wine color of the urine is noticed by the 
men themselves as an early sign of poisoning. Hemoglobin has been demonstrated 
in the urine, also hydrobilirubin and hematoporphyrin. A reduction compound is 
found in the urine in some cases and serves as a proof that absorption is taking 
place. These are para-amino phenol from aniline, the nitrobenzenes and nitro- 
anilines, amino-2-nitro-4-phenol from dinitrophenol, dinitro-hydroxylamino tolu- 
ene (Webster test227) and 2.6-dinitro-4-aminotoluene (Snyder and von Oettingen 
test299) from trinitrotoluene. 
Certain of the nitro and amino compounds are conspicuous as causes for occu- 
pational poisoning. Thus the British factory inspectors list cases almost every 
year from exposure to the intermediates, DNB, DNT and TNT, from the making 
and use of aniline, from aniline-black dyeing and from dinitrochlorbenzene. 
“ Anilinism ” is the term under which these cases are listed, and under this term 
reports have been made since 1930. 
Some of the histories show clearly that skin absorption plays an important 
part in such poisoning. For instance a workman carrying a bucket of aniline 
slipped and splashed it over his coat and arms. He took off his coat and washed 
his arms, but then put on his coat again. Some hours later he become cyanosed, 
was dizzy and drowsy and, when removed to the hospital, was only semiconscious. 
A case which illustrates this point was seen by one of us (R.T.J.). This was 
in a chemist’s assistant who spilled nitrobenzene on his trousers and almost at 
once fell to the floor. He was rushed to the hospital in his soaking clothes and 
was unconscious when he arrived with respiration at first rapid, then slow and 
irregular, pulse feeble, heart sounds distant and weak, cyanosis marked. A sample 
of blood was of a deep brown color. He died an hour and a half after the accident. 
Postmortem examination revealed nothing of note. 
Vol. IV. 944 
Volatile liquids such as aniline act more rapidly than solids, as for instance AROMATIC OR BENZENE SERIES OF SOLVENTS 
659 
trinitrotoluene. When poisoning is slower, there is a toxic action on bone marrow 
and liver, and acute degenerative hepatitis may result with or without aplastic 
anemia. TNT is the substance which has given rise to the great majority of such 
cases in the literature, but an unusually slow form of dinitrobenzene poisoning 
has been known to result in the same liver lesions. 
Prosser White329 has described dinitrobenzene poisoning as he saw it in British 
explosives manufacture in World War I. The poison passes rapidly through the 
skin and also is inhaled as vapor. A workman, who breathed for ten minutes 
the air in a flue through which pure dinitrobenzene had been poured from the 
mixing pans, died eighteen hours later from the effects. Such cases were rare, but 
chronic poisoning was far from rare. This was characterized by a severe form 
of anemia, the skin was dusky yellow, the conjunctivae jaundiced, the man looked 
as if he were suffering from partial asphyxia, his muscles were wasted, sensation 
dulled, paresis of the hands was marked, there were paresthesias, hyperesthesia 
and defects of vision. 
Almost all of the compounds of this series seem capable of setting up a more 
or less severe dermatitis, although some are far worse than others. According to 
White329 the intermediates, which are responsible for lesions of the skin, are the 
following in the order of their injurious action; dinitrochlorbenzene, dinitro- 
phenol, p-nitrosophenol, p-nitrosocresol, diaminophenol, p-nitroaniline, p-amino- 
phenol. 
Dinitrophenol 
Dinitrophenol 1-2-4 or alpha dinitrophenol was a constituent of the French 
explosive melinite and is also an intermediate in dye production; for a while it 
came into use in the treatment of obesity. It is a powerful stimulant to 
metabolism. According to the French investigators, Etienne Martin and A. Meyer 
(see Perkins253), the mechanism of intoxication consists in an enormous increase 
in the intracellular oxidation processes with consequent increase of gaseous ex- 
change from ten to twelve times the normal and rise of body temperature in spite 
of the distension of skin capillaries and profuse sweating. This excessive oxida- 
tion affects metabolism and nutrition and damages liver and kidney cells. Un- 
changed dinitrophenol and the reduction products, amino- and diamino-nitro- 
phenol, are found in the urine. There are absolutely no pathological findings at 
autopsy. 
The use of alpha dinitrophenol for the treatment of obesity has led to a num- 
ber of cases of serious poisoning with symptoms such as those described above 
and in 4 cases with agranulocytosis (see Silver289). The pronounced toxicity of 
this compound should lead to great caution in its industrial use, which unfortu- 
nately is increasing. 
Vol. IV. 944 660 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Dinitrocresol 
Another compound of increasing importance in industry is 3.5-dinitrocresol, 
which has an action similar to that of dinitrophenol, being in the opinion of some 
observers less toxic, of others more toxic. It has been used also in the treatment 
of obesity and has been responsible for severe and even fatal poisoning (von 
Oettingen242). Industrial poisoning has been described by a German (Schwarz280) 
and recently by J. M. McDonald211 of the Bureau of Occupational Diseases of 
the Baltimore City Health Department. McDonald’s case was in a negro, whose 
palms and soles were dyed a deep canary yellow, and who recently had lost 20 
pounds. He had a temperature of 102 0 F., a phenomenal basal metabolism rate 
of 400 plus, rapid pulse, rapid respiration, profuse sweating, shortness of breath 
and cough. An examination of his work place showed he had been exposed to 4.7 
mgm. of dinitrocresol dust per cubic meter of workroom air per day. The man 
recovered. 
Paraphenylenediamine 
Paraphenylenediamine is used very generally as a dye for furs, known in 
industry as ursol. It is a notorious cause of dermatitis both in fur dyers and fur 
wearers, and also it has been known to set up in susceptible individuals typical 
attacks of bronchial asthma, which are attributed by Hanzlik125 to direct irrita- 
tion of the air passages, by Mayer204 and others29 to an allergic reaction. 
Nitroanilins, para and meta, are important intermediates in dye manufacture, 
and cases of severe poisoning have been reported following overexposure to fumes 
or dust. The symptoms are characteristic of the aniline group as already de- 
scribed. 
Chlorotoluidine 
An amino compound, 5-chloro-2-toluidine, has caused a good deal of trouble 
recently in some English factories, the intoxication being characterized by cyano- 
sis, tachycardia and hematuria with subsequent albuminuria, strangury and fre- 
quent micturition. The bladder is affected chiefly, the kidneys more slightly. 
For further discussion of this and for the 4-chloro and 6-chloro isomers see von 
Oettingen242. 
Betanaphthylamine 
The amino derivatives of naphthalene are important dye intermediates and 
have been the subject of much study because of the part one of them, betanaph- 
thylamine, plays in the production of bladder tumors. In the experience of one 
of us (A.H.) both are capable of producing symptoms of “ anilism ”, but in 
Vol. IV. 944 AROMATIC OR BENZENE SERIES OF SOLVENTS 
661 
practice the alpha isomer gives little trouble, while the beta may cause cyanosis 
and frequent micturition from the presence of the carcinogenic substance. 
Trinitrotoluene: TNT 
This was studied exhaustively during World War I, especially by the British, 
and experience during World War II has not added much to the facts accumulated 
in 1914-18. It is highly toxic both locally and after absorption. It produces a 
sago-grain dermatitis, intensely irritating with exfoliation, appearing on hands 
and forearms chiefly but wherever the skin is exposed or touched with TNT 
smeared fingers. In American plants there was invariably an increase of derma- 
titis in hot weather, not only because arms and necks were more exposed, but 
because the sweat helped to dissolve the TNT dust and quicken its absorption. 
Because TNT is absorbed through the skin, the mixture of nitrate of ammonia 
and TNT, known as amatol, is more productive of poisoning than pure TNT. 
Ammonium nitrate is hygroscopic and keeps the skin of hands and forearms moist, 
thus dissolving the TNT. 
TNT belongs to the group of poisons which enter through the skin, and which 
form methemoglobin317. Cyanosis is a characteristic symptom. The usual case of 
“ TNT sickness ” shows pallor, bluish lips and lobes of the ears, breathlessness, 
feeling of tightness in chest, abdominal pain, nausea, headache, lassitude, anorexia. 
Jaundice is a serious sign of liver damage, and no worker, who has recovered 
from such an attack, should ever be exposed again (Hilton and Swanton139). 
TNT affects the liver, the bone marrow and the vascular endothelium in varying 
degree199. Severe intoxication therefore results, in acute toxic hepatitis, toxic 
purpura and more rarely, aplastic anemia. Evans69 reports 7 cases of TNT 
jaundice with 3 deaths. Autopsy revealed acute yellow atrophy of the liver and 
hyperplastic bone marrow. 
A recent article (March, 1944) by Coyer44 reports 7 cases of TNT poisoning 
of the gastrointestinal type, one of them fatal. In this case autopsy revealed 
severe jaundice, cirrhosis of the liver with superimposed hepatitis and hemor- 
rhage into the gastrointestinal tract. 
In World War I physicians in charge of TNT plants depended on the Webster 
test227 to give warning of approaching danger. This color test revealed the reduc- 
tion product. It is, however, proof only of absorption. Kennedy and Ingham161 
prefer a simple test for the determination of porphyrinuria, which shows intoxi- 
cation. Snyder and von Oettingen299 propose a new test more sensitive than the 
Webster test for a reduction product in the urine, which they tentatively identify 
as 2.6 dinitro-4-aminotoluene. 
Experience in England indicates that women are more susceptible than men 
Vol. IV. 944 662 
INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
to TNT, colored men less than white. The greater susceptibility of youthful 
workers was demonstrated in American plants during World War I116. 
T etryl 
Tetryl is trinitrophenylmethylnitramine, a very important military propellant. 
Tetryl dermatosis was recognized during World War I as a very troublesome 
affection, but it was believed that this was the only form of poisoning to be looked 
for in tetryl workers. More careful studies made during 1943 reveal the fact 
that systemic effects also may occur. Witkowski and his colleagues345 report no 
less than 1,258 cases of industrial illness due to tetryl in a force of over 5,000 
workers. The chief complaint was of a dermatitis, usually on the face and neck. 
Epistaxis was a common complaint, and small ulcerations of the nasal mucosa 
furnished the cause. A systemic effect was seen also. Anorexia, mild nausea, 
flatulence and abdominal cramps occurred in 10 per cent, of all exposed; dry 
cough and pain in the chest, headache, irritability, sleeplessness, lassitude were 
frequent complaints. Three cases were serious enough for hospitalization. All 
had a history of severe tetryl dermatitis, which recurred with increased intensity 
on a second accidental exposure. The authors emphasize also the occurrence of 
rapidly developing secondary anemia. Noro238 of Finland observed anemia in 
109 of 163 tetryl workers. 
Chlor Compounds of Benzene: Nitrochlor 
Chlor compounds of benzene are used largely in industry, notably paradichlor- 
benzene, which is a constituent of drugs, anti-moth mixtures, insecticides, etc. 
It gives rise to dermatitis, but if systemic symptoms arise in a sprayer of this 
compound, it would be well to learn what is the liquid vehicle, for it might be 
benzene, carbon tetrachloride or carbon disulphide. 
Nitrochlor compounds are more irritating to the skin than those without the 
nitro group, and they produce systemic poisoning with methemoglobinemia of 
like character but less severe than that of nitrobenzene (von Oettingen242). 
Diphenyls 
Diphenyl, an important intermediate for the newer plastics, is two benzene 
rings linked together and is made by bubbling benzene through molten lead. At 
ordinary temperature it is solid, which may explain why no trouble has been 
reported from its use. This is not true of its important chlorine derivatives. 
Chlorinated diphenyls are used for the same purposes and often in conjunc- 
Vol. IV. 944 AROMATIC OR BENZENE SERIES OF SOLVENTS 
663 
tion with chlorinated naphthalenes. In their study of the latter Drinker and his 
colleagues55 tested also chlorinated diphenyls and chlorinated diphenyl oxides. 
They found that the former bodies act much as do the naphthalenes of low 
chlorine content, and that the same limit of concentration in the air may be per- 
mitted, 100 mgm. per 10 cubic meters of air. For the chlorinated diphenyl oxides 
the limit should be the same as that for the higher chlorinated napthalenes, 50 
mgm. per 10 cubic meters. Greenburg" has outlined the proper methods of pro- 
tection against injury from these compounds. 
Aniline Tumor of the Bladder 
An interesting and long unexplained manifestation of slow chronic poisoning 
by coal tar derivatives is the so-called aniline tumor of the bladder, a papillomatous 
growth which undergoes carcinomatous degeneration. The German dye industry, 
since it is the oldest and much the most extensive, was the first to discover that 
men in contact with certain dye intermediates suffered in abnormal proportion 
from cancer of the bladder. By 1920 the reported cases numbered 177, and each 
year new ones have been added. Animal experiments were not fully convincing, 
but it was soon established that whatever was the elimination product in the urine 
responsible for these tumors, it belonged to the amino group, not the nitro. 
Hueper and his colleagues143 succeeded in producing neoplastic lesions of the 
bladder in 9 of 16 dogs treated with beta-naphthylamine. Morigami and Nisi- 
mura228 had a like success with orthotoluidine and benzidine. Cases develop 
chiefly in men exposed to aniline, benzidine and beta-naphthylamine, but other 
amino compounds also have been accused. Usually it is only after an exposure 
of many years that the tumor appears, and in some cases not until years after all 
work with amino compounds has ceased. 
In England the first cases of aniline tumor of the bladder appeared much later 
than in Germany because the industry is of more recent origin (Wignall331, 
Macalpine194). According to Legge183 23 fatal cases had been reported in Eng- 
land up to the end of 1931. In the United States the manufacture of coal tar 
dyes did not amount to much before the outbreak of World War I shut off the 
supply from Germany. Twenty years later the first American publications on 
aniline tumors of the bladder appeared in the shape of a number of articles by 
the group of physicians associated with the E. I. du Pont de Nemours Company 
(Ferguson and associates75). In the experience of these men the active agents 
have been benzidine or beta-naphthylamine or alpha-naphthylamine containing 
about 5 per cent, of beta. The unusual feature of this report is that it is based on 
532 cystoscopic examinations, which enabled the physicians to discover 25 posi- 
tive fases, or 4.5 per cent., and 16 others with hemorrhagic areas in the bladder. 
Voi . IV. 944 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
The age of these men varied from 30 to 60 years and the exposure from 4 to 18 
years. Of the 25 tumors 14 were simple papillomas, 8 carcinomas, and 3 were 
doubtful. 
Neither the Germans nor the English use cystoscopic examination as a routine 
measure, believing that the workmen would not submit to it, so they are obliged 
to depend on the detection of blood in the urine. After blood has been found 
three times the cystoscope is used. Gehrmann75 of the du Pont Company is 
convinced that a cystoscopic examination should be made once a year in all men 
exposed to the dangerous compounds and immediately, if blood appears in the 
urine. They no longer shift positive cases to other work, for the German experi- 
ence has shown that once a man has been exposed removal does not lessen the 
danger to him and only results in the exposure of a new man. Even if a workman 
is discharged, he should be given an examination at least once a year thereafter, 
if he had worked with the tumor-producing compounds. 
Aniline Dyes 
The substances used in the production of coal tar dyes, to mention only the 
toxic ones, are the “ crudes ”, benzene, toluene, xylene, phenol, which are treated 
with mineral acids, alkalies and certain compounds of the aliphatic series such 
as methyl alcohol, dimethyl sulphate, formaldehyde, methyl chlorides; reduction 
is effected by means of nascent hydrogen produced from zinc and hydrochloric 
acid in the course of which AsHo may be given off, nitration by nitric acid and 
oxidation by potassium chlorate and lead peroxide. The resulting compounds, 
known as “ intermediates ”, are chiefly nitro, chlor and amino compounds322. Re- 
duction is now being replaced by amidation in some plants. Aniline can be 
produced by amidation of benzene with ammonia, and this process does not carry 
any danger from AsH3. 
The finished dyes for the most part are quite harmless, and the dermatoses 
that sometimes appear in. dye makers and dyers should be attributed to over-harsh 
methods of cleaning the hands (White329). Commercial aniline, which may con- 
tain nitrobenzene, has been used for printers’ ink, hair dyes and floor polishes, but 
such uses are rare now. A new use, however, for aniline is as a stabilizer of tri- 
chlorethylene in degreasing tanks to prevent the break up of tri with the formation 
of metal-corroding hydrochloric acid. 
Carbon Disulphide 
Carbon disulphide for many years has played an important part in the rubber 
industry in Eurone and a less important part in American rubber manufacture. 
Vol. IV. 944 CARBON DISULPHIDE 
It is necessary to incorporate sulphur in crude rubber, the process being known 
as vulcanizing, and this may be done either by adding flowers of sulphur and then 
heating the mass, or by exposing rubber to the action of sulphur monochloride 
either in vapor form, or by dipping it in the liquid or by painting. The carrier for 
sulphur monochloride usually was carbon disulphide. American manufacturers 
always have preferred the heat cure for rubber, while the Europeans preferred the 
so-called cold cure with carbon disulphide. It is this last compound that has given 
to European rubber manufacture a very bad reputatiqn, and the literature is full 
of reports of carbon disulphide poisoning in rubber workers. Recently these 
cases have diminished in number as hygienic conditions have improved, but their 
place has been taken by a new class of workmen, the makers of artificial silk by 
the viscose process. This is the process used in Europe and the Orient and also 
in this country in the production of “ viscose rayon ”. 
Carbon disulphide was recognized as an industrial poison by the French almost 
one hundred years before psychiatrists in the United States were willing to do so. 
Payen248 who first described its action in 1851 was followed by Delpech51 in 1856, 
the latter describing 24 cases in rubber workers and also experimental poisoning 
in dogs. Germany followed with a number of very thorough studies of this poison, 
whose manifestations were said to be as varied as those of lead (Koester170). 
Then many reports began to come from Italy264, some frorn England, France235, 
Holland, Japan, but up to the early years of this century only one article had 
been published in the United States, that of Peterson255 in 1892 describing carbon 
disulphide poisoning in rubber workers. 
Recently the picture has changed markedly, and there are now a number of 
American publications on the clinical and biochemical action of this poison on 
viscose rayon workers and on experimental animals. The most important of 
these are contained in a series of studies, clinical, anatomical and experimental, 
conducted by a group of members of the faculty of the University of Pennsyl- 
vania Medical School under the leadership of F. H. Lewey252. These are based 
on an examination of 120 men employed at the time in those processes of rayon 
manufacture, which involve exposure to fumes of carbon disulphide, and on ex- 
perimental intoxication of animals188. Mild forms of poisoning were found in 
nearly 60 per cent, of spinners, whose exposure is not high, while in churners, 
whose exposure is much higher, severe poisoning was found in 20 per cent, in one 
plant, in 44 per cent, in the other. 
Lewey and his colleagues found that chronic carbon disulphide intoxication 
may involve all parts of the central and peripheral nervous systems, beginning 
with psychic symptoms, later peripheral neuropathy and damage to the cranial 
nerves, decrease of corneal and pupillary reflexes as well as pyramidal and extra- 
pyramidal signs. Varying degrees of Parkinsonism were observed also. All these 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
had been described already in the foreign literature, especially by Germans and 
Italians. 
The commonest form of carbon disulphide poisoning is neuritis187, which may 
affect any of the nerves but most commonly involves the nerves of the limbs and 
certain of the cranial nerves, optic, auditory. Both the motor and the sensory 
nerve fibers are affected, causing abnormal sensations and loss of power. For 
evidence of sensory involvement we must depend on the patient’s word, but 
motor nerve injury is revealed by objective tests of known reliability. 
Usually the trouble begins with a sensation of crawling over the skin, formi- 
cation, a tendency for the arms and legs to “ go to sleep ”, a sensation of coldness 
and heaviness and a curious feeling that the hand and foot belong to someone else. 
Pain is associated with these symptoms and tenderness along the nerve trunk, 
and at the same time tests may show touch, pain and temperature sense to be 
heightened, rarely diminished. 
Sometimes irritative symptoms prevail, constant or paroxysmal pain in the 
distribution of one or several nerves or sometimes generally diffused. During 
the night pain in the legs may reach an intolerable intensity. Aching muscles, 
cramps and sharp pains shooting up and down the legs may make sleep im- 
possible. 
Any of the nerves may be affected, but those more usually involved are the 
radial and ulnar in the upper limbs, the sciatic and external peroneal in the lower. 
Lewey’s group found that areas supplied by the anterior and lateral cutaneous 
nerves of the thigh often were the seat of hypersensitivity. 
These symptoms are followed soon by signs of motor nerve involvement. 
Lewey’s group found such signs more frequently than those of sensory nerve in- 
jury. The victims complained of early fatigue, gradually increasing loss of 
strength and especially difficulty in climbing stairs or walking up hill. Weakness 
in the legs appears earlier and is complained of more frequently than weakness in 
the arms. Some observers have found the extensor muscles more severely in- 
volved than the flexor; others find the reverse to be true. Sometimes there is an 
exaggeration of the deep tendon reflexes, biceps, triceps, patellar, Achilles, espe- 
cially in the early stages, but more often the reflexes are diminished. The muscles 
are weak, and as time goes on, wasting appears, more or less marked according 
to the severity and duration of the poisoning. The “ chronaxia ” test, which 
measures the time it takes to produce excitation of the nerve-muscle apparatus 
together with the strength of current required to produce it, was applied by 
Lewey’s group. In a few individuals it showed an increase of electric irritability, 
but in the majority of cases there was a decrease, sometimes very marked. 
Lewey found evidence of peripheral neuritis in 87 per cent, of 120 men ex- 
posed to fumes of carbon disulphide. The course of carbon disulphide neuritis 
Vol. IV. 944 CARBON DISULPHIDE 
is slow, slower than that of alcoholic, rheumatic or syphilitic origin. Recovery 
proceeds with extreme slowness, and the prognosis must be guarded, because the 
atrophy, pain, paresthesias, etc. may persist even if the victim quits his job. 
The most striking and the most disastrous effects of carbon disulphide poison- 
ing are upon the brain. The mental symptoms run the gamut from simple irri- 
tability and depression to manic-depressive insanity. If the basal ganglia are 
involved, Parkinsonian palsy occurs. In typical cases the attack of active or 
violent mental derangement comes on fairly suddenly, but careful questioning 
of the family and working mates always will bring to light an earlier stage of 
emotional upset, irritability, depression and complaint of loss of memory. During 
this stage there may be excessive sexual excitation, which soon is followed by loss 
of libido and even impotence. 
Even in milder poisoning changes in personality are evident, especially in the 
man’s relations with his wife and children, and the victims realize this but are 
powerless to help it. Sleeplessness, horrid dreams, loss of memory are frequent 
complaints. Neuritis, shown by weakness, paresthesias, pain, is the commonest 
form of intoxication by carbon disulphide; disturbances of vision, though rarely 
of a pronounced character, are present often and give valuable aid in the diagnosis. 
Diminution or loss of the corneal reflex is stressed by Teleky22, central scotoma 
for color, abnormal color vision, loss of visual acuity, paralysis of accommodation, 
all have been described. 
Lewey and his colleagues188 made a survey of the changes in the nervous sys- 
tem in man and in experimental animals following carbon disulphide poisoning. 
“ A comparison of the two discloses the fact that in the human nervous system 
one finds scattered changes in the ganglion cells of the cerebral cortex of varying 
degree, depending on the severity of the intoxication, disease of the basal ganglia 
and peripheral nerves, and evidence of vascular involvement; in the experimental 
animal there are more extensive damage to the cerebral cortex and basal ganglia, 
injury of the Purkinje cells, vascular changes, minor damage to the spinal cord 
and involvement of the peripheral nerves.” 
Ferraro, Jervis and Flicker76 also produced experimental carbon disulphide 
intoxication in cats. They found the most important lesions to be a diffuse vas- 
cular involvement of a productive type, leading to endarteritis, occlusion of the 
vessel and secondary softening and to diffuse neurocellular changes, ranging from 
chromatolysis to severe degeneration scattered all over the brain and cerebellum 
but most evident in the corpora quadrigemina, the cerebellar and vestibular 
nuclei. 
Gordy and Trumper94 reported in 1940 21 cases of chronic carbon disulphide 
intoxication in workers in American viscose rayon factories from exposures lasting 
on an average 10 years. Encephalopathic symptoms were seen in 90 per cent., 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
subjective eye disturbances in 67 per cent, with blurring of the disks in 30 per 
cent; about 75 per cent, had lessened libido, 70 per cent, various degrees of 
neuropathy affecting the limbs and over two thirds had gastrointestinal disorders. 
In 55 per cent, the symptoms indicated localized lesions of the central nervous 
system including Parkinsonism. 
Finally Weise327 has published an extensive investigation of the gastrointes- 
tinal diseases of German rayon workers, especially peptic ulcer, to which he was 
led by observing the large proportion of gastrointestinal cases among rayon and 
rubber workers in Berlin. Among 100 such cases 66 were from the carbon disul- 
phide departments of rayon factories. Comparing them with other textile work- 
ers through sickness insurance records he found that the latter had only an aver- 
age of 2.1 to 3.2 per cent, cases in a year, while the rayon workers averaged 17.7 
per cent. Weise produced marked gastrointestinal injury in animals. 
The American Standards Association has established 20 parts per million as 
the maximum allowable concentration of carbon disulphide. 
Synthetic Rubbek 
Synthetic rubber production utilizes many of the chemical compounds already 
familiar in connection with natural rubber manufacture, solvents, anti-oxydants, 
accelerators. The new toxic substances according to Wilson339 and to Mallette197 
of the Firestone Company, are three, namely, acrylonitrile or vinyl cyanide, buta- 
diene or vinyl ethylene and monomeric styrene or phenylethylene. The first has 
been described already under the cyanides. Butadiene is a gas at ordinary tem- 
peratures, and it must, therefore, be kept under pressure, which makes it unlikely 
that exposure would occur under usual conditions. It is mildly narcotic below 
the lower explosive limit, 2.2 per cent, or 22,000 parts per million. The vapors 
cause irritation of eyes, nasal passages, throat and lungs, sometimes with cough 
and also a sense of fatigue and drowsiness but no evidence of a cumulative action. 
Mallette considers that no permanent effect will follow exposure to cqncentrations 
below the explosive limit, which have occurred fairly often in the experimental 
laboratory without harm. 
Styrene was tested by Spencer and his colleagues300 of the Dow Chemical Com- 
pany, and it was found that vapor concentrations acutely dangerous to animals 
range from 2,400 parts per million for an 8 hour exposure to 10,000 parts per 
million for 30 to 60 minutes. Immediate death results from a primary action on 
the central nervous system, delayed death from pneumonia. In man there is 
eye and nose irritation, which Mallette believes should be ample warning of 
danger. He has seen also light narcotic symptoms follow inhaling styrene fumes. 
Wilson says that a year’s exposure to styrene, not over 500 parts per million, does 
Vol. IV. 944 TOBACCO: NICOTINE 
not result in any sign of chronic disease. The rubber industry has suggested 200 
parts per million as a safe limit. 
The Public Health Service has tested a fourth compound, chlorobutadiene, 
known as chloroprene, the starting point for Duprene rubber. It is toxic to ani- 
mals, causing severe degenerative changes in the organs, depression of the central 
nervous system and low blood pressure244. 
Tobacco: Nicotine 
The tobacco industry has a very bad reputation, and in all foreign textbooks 
on industrial disease this is listed as one of the dangerous trades, yet there are 
surprisingly scanty data on which to base such a belief. The assertion is made 
often that tobacco workers suffer inordinately from pulmonary tuberculosis, from 
nervous disorders including dimness of vision, and that women workers have an 
unduly high rate of pelvic disease. It seems to be true that there is an excessive 
tuberculosis death rate among tobacco workers even in this country, where the 
industry is for the most part carried on in excellent, highly mechanized factories, 
but the cause is not the dust; rather it is the low wage and the fact that tobacco 
work attracts persons of poor physique (Dublin07, Landis179). Long193 observed 
1,246 tobacco workers over a period of ten years comparing them with a control 
group of 1,008 and found no evidence that the former group had an excess of 
pneumoconiosis. He seems to have been the first to use the x-ray and fluoroscope 
in investigating tobacco workers. Nervous disorders with nausea and vomiting 
are a common occurrence among the newly employed, but they soon grow accus- 
tomed to the effect, as smokers do. Burstein29 found that workmen in Russian 
factories breathe dust representing somehat less nicotine than they would absorb 
by smoking 20 cigarettes. A few cases of blindness from long contact with nico- 
tine have been recorded, but they are not beyond question. An excess of pelvic 
disease in women tobacco workers seems to be shown by the sickness insurance 
statistics of Germany and Austria, whatever the explanation may be. 
Stevenson301 has been able to observe acute nicotine poisoning in a California 
factory, which manufactures insecticides. From a study of io cases of acute 
poisoning and observation of the employees in general he concludes that the symp- 
toms caused by nicotine are not the same as those caused by smoking tobacco, for 
smokers are no less susceptible to industrial nicotine poisoning than non-smokers. 
The symptoms show a direct action on the spinal cord, medullary centers and the 
sympathetic system. At first there is excessive secretion of saliva and tears with 
watery discharge from the nose; then headache comes on with giddiness, numb- 
ness, disturbed vision, torpor and rapid respiration followed in about half an hour 
by faintness, intense depression, cold extremities, nausea, vomiting and increasing 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
dyspnea. He has not seen the clonic convulsions described by others. Recovery 
is rapid, provided the victims are kept strictly at rest. Usually they are able to 
come back to work in 48 hours. Nicotine can be absorbed through the skin 
(Wilson338). 
Radioactive Substances 
The use of radioactive substances in industry is very recent and as yet not 
extensive. The accidental exposure of workers to radiation in mining radioactive 
ores is much older, but the discovery of the part played by emanations of radium 
in the sickness and death of these miners was made only lately. Even now the 
industrial uses of radiation are few, but the injuries, that have resulted in some 
cases, were so spectacular as to arouse wide public attention and lead to strenuous 
efforts of control, much as the occurrence of “ phossy jaw ” in a relatively small 
proportion of match makers led to a world-wide campaign against the use of white 
phosphorus. 
Roentgen rays may be used industrially either for radiography or for fluoros- 
copy, but the latter is much better adapted for such purposes and is almost always 
used. The strength of the rays varies according to the thickness of the material 
to be penetrated; soft rays will do to show the position of the metal plate in rubber 
heels; hard rays must be used to reveal flaws in castings. Undoubtedly the chief 
source of x-ray injury is still the use of these rays in medical practice, although 
now the proper measures for protection are so well known that instances of serious 
injury are rare. In industrial use there is far more risk of minor injuries, of x-ray 
lesions of the skin, since the precautions are likely to be far from perfect, but it is 
doubtful if there will be cases of such severity as have occurred among radiologists, 
for the workman has not so strong a motive to keep on at work after he has dis- 
covered that it is dangerous. So far the only instances of strictly industrial x-ray 
lesions that have come to light are skin lesions of more or less severe character. 
These, which are usually on the fingers, are intensely painful even when quite in- 
significant in appearance and are very obstinate. As we know from non-industrial 
cases, such lesions may undergo cancerous change years later (Porter260), but 
as yet no cases of that sort have been reported from industry. 
Radium. — This section is based largely on the studies of J. C. Aub6 and 
R. D. Evans68. According to Evans68 records show that several hundred peo- 
ple were killed through various types of radium exposure prior to 1930. Since 
then the number of persons engaged in the industrial handling and application 
of radium has increased about fifty fold. Radium is formed by the natural radio- 
active decay of its ultimate parent, uranium, which occurs in commercial quan- 
tities in a few isolated mineral deposits. Radium is the fifth in a long series of 
decay products of uranium. 
Vol. IV. 944 RADIOACTIVE SUBSTANCES 
In its radioactive disintegration radium emits alpha rays. For practical pur- 
poses the alpha ray can be thought of as an energetic atomic bullet whose range 
is about 50 microns in living tissue, and which can do lethal damage to most of 
the cells traversed along its path. After the radioactive decay of radium by its 
emission of an alpha ray, the residual is an atom of radon. Radon is the heaviest 
member of the group of noble gases, helium, argon, etc., and is, therefore, chemi- 
cally inert. However, physically radon, like radium, is radioactive and emits 
alpha rays in its disintegration. Each decaying atom of radon experiences seven 
subsequent radioactive transformations before finally becoming a stable atom of 
lead. In the commercial use of radium radioactive equilibrium usually is present; 
then each of the decay products, radon, radium A, radium B, radium C and 
radium C', has the same rate of radioactive emission as radium. 
The alpha radioactivity of radium in equilibrium with its decay products, 
therefore, is four times as great as the alpha radioactivity of radium element alone. 
From the standpoint of toxicity, that is cell damage produced by alpha rays, 
the decay products of radium are three times more hazardous than radium itself. 
All salts of radium have the same toxicity as the elemental radium which they 
contain. 
In the preparation of self-luminous compound a small amount of some radium 
salt, usually radium chloride or radium bromide, is mixed with a binding agent 
and specially prepared and finely powdered zinc sulphide crystals. The alpha 
rays emitted by radium and its decay products bombard the zinc sulphide crystals 
and cause them to emit visible light in tiny flashes, one for each alpha ray. The 
integrated effect of thousands of such tiny flashes of light per second is that of 
a uniform emission of light. 
Zinc sulphide emits a visible light when irradiated by ultra violet light. For 
this reason a mixture of zinc sulphide and binder is used also as a fluorescent 
paint without the addition of any radium to the mixture. This fluorescent paint 
is applied to a number of the markings of modern military instruments. Conse- 
quently a number of dial painting concerns have both “ fluorescent ” and “ ra- 
dium ” painting going on in different parts of the same plant. In safeguarding 
the health of the radium painters this fluorescent painting is a most fortunate 
circumstance, because it provides a simple means of rotating personnel between 
radium and non-radium work. 
Industrial exposure to radioactive substances occurs in mining radioactive 
ores, handling and testing the products of the ores, making up radon seeds and 
making and applying luminous paint to the figures on time pieces and to parts of 
apparatus. Such exposure has resulted in pulmonary carcinoma, necrosis of bone, 
malignant growth of the bone and primary blood diseases of various kinds. Car- 
cinoma of the lungs is the kind seen in miners of the Schneeberg region of Saxon 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Switzerland, where the cobalt arsenide ores are radioactive, and for more than a 
century it has been known that a large proportion of the miners died prematurely 
of lung disease with wasting. The discovery that the disease was pulmonary 
carcinoma was made in 1878, confirmed in 1913 and again in 1926268. At first 
the arsenic in the ore was supposed to be the carcinogenic agent, but the later 
studies attributed this action to the radioactivity of the ore. The same ore is 
found on the Bohemian side of the mountain, and pitchblende is now mined there. 
Here also the miners suffer from pulmonary carcinoma257. 
In September 1924 Theodore Blum17, a dentist, described before the American 
Dental Association a form of necrosis of the jaw with severe buccal infection in 
dial painters applying a luminous paint, and he attributed it not to phosphorus 
but to the radioactive substances in the paint. He was the first to discover the 
real cause of this affection, which had attracted the attention of other dentists in 
northeastern New Jersey but had been diagnosed as “ phossy jaw ” or Vincent’s 
angina or syphilis. In some of these cases there was evidence also of a profound 
injury to the blood-forming tissues. 
The cases of radium necrosis and aplastic anemia among these women dial 
painters attracted widespread interest and much controversy, from which, how- 
ever, a clear picture gradually emerged37. The chief credit must be given to Mart- 
land200, who not only published the first description of the pathology of this new 
occupational disease but followed year after year the fate of the women, who 
had been exposed to the luminous paint, and thus discovered the later manifesta- 
tions of this kind of radium poisoning. In the early cases, which developed fairly 
rapidly, there was a rarefying osteitis of the bones of the jaw with sepsis and 
anemia, usually of the aplastic type. In cases developing later there was necrosis 
of other bones, the femur and the humerus (Martland200), the cranial bones (Flinn 
and Seidlin78). Still later, in 1931, Martland and Humphries202 reported 5 in- 
stances of osteogenic sarcoma among 18 victims of fatal radium poisoning in New 
Jersey and Connecticut, which would make 27 per cent., while the incidence of 
osteogenic sarcoma in the general population is only 0.07 per cent. Three former 
dial painters still living at that time had bone lesions which were very suspicious 
of neoplasm. 
Silvertone291 says that the actual dose required to produce radioactive cancer 
is not known, but it is known that for its production there must be either a long, 
continuous exposure or many intermittent exposures. He does not believe that 
the radionecrotic tissue becomes cancerous, but cancer may arise in the viable 
tissue nearby, where degenerative and regenerative changes continue side by side. 
Both are progressive even after the radioactive agent is withdrawn. The type of 
neoplasm depends not on the nature of the injurious agent but on the type of 
Vol. IV. 944 CARBON MONOXIDE 
tissue affected. The neoplasm arises in the irradiated tissue, but once established 
it behaves like any other of similar structure and anatomical site. 
As for the blood changes the history of radium poisoning in some of the famous 
radiologists had shown that such changes might be very varied in character. 
Martland201 saw, in addition to cases of typical aplastic anemia, 5 of leucopenic 
anemia of the regenerative type and von Jagic153 reported 3 cases of lymphatic 
leucemia; Carman and Miller34 one. 
When taken into the body, radium behaves biochemically like calcium. A 
portion of the ingested radium eventually is deposited in the bones. The alpha 
rays from radium and from its decay products, whidh build up in the bones, bom- 
bard the blood producing centers, the bone building cells, osteoclasts and osteo- 
blasts, and the bone structure. 
In chronic radium poisoning, where the body contains 1 to 10 micrograms of 
radium fixed in the skeleton, there are usually no clinical symptoms until some 5 
to 15 years after the exposure. There is often no deviation from a normal blood 
count, and tissue abnormalities are mild or absent. 
Because of the wide variations in body resistances, some patients with only 2 
micrograms of radium may be more quickly and more seriously affected than 
others containing as much as 20 micrograms of radium. Unpublished measure- 
ments by J. C. Aub and R. D. Evans now include 7 human cases, in which more 
than 0.02 micrograms and less than 0.5 micrograms of radium have been carried 
for some 7 to'2 5 years without the appearance of any clinical symptoms of chronic 
radium poisoning. On the other hand, several unpublished cases seen by these 
workers and others measured by Martland with the same or similar analytical 
apparatus, have resulted fatally, when the radium burden was between 1.2 and 2 
micrograms of radium. 
Based on these observations a committee called together in 1941 by the 
National Bureau of Standards tentatively established 0.1 micrograms of radium 
fixed in the body as the tolerance value for man. This figure replaces tolerance 
values of 10 micrograms and 1 microgram recommended by individual observers 
a number of years ago before adequate physical methods were available for de- 
tecting smaller quantities of radium in living persons. 
Carbon Monoxide 
Carbon monoxide is the oldest of the industrial poisons, for it must have 
attacked the first men who used heat to break stone for implements or who burned 
wood with little air to make charcoal. It is formed whenever combustion takes 
place with insufficient oxygen. 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
In industries of modern life the chief sources, according to Sayers and Yant, 
'are these: 
Blast furnace stack gas 28.00 per cent. CO 
Bessemer furnace stack gas 25.00 “ “ “ 
Arc furnace, melting aluminum 32.00 “ “ “ 
Blasting with dynamite 1.20 “ “ “ 
Combustion of dynamite 28.00 “ “ “ 
Explosion of TNT 60.00 “ “ “ 
Coal gas undiluted with air 16.00 “ “ “ 
Carburetted water gas undiluted with air 30.00 “ “ “ 
Blue gas undiluted with air 40.00 “ “ “ 
Producer gas from coke 25.00 “ “ “ 
Producer gas from oil 5.00 “ “ “ 
Automobile exhaust gas, average * 7.00 “ “ “ 
At peak hours of traffic on crowded streets tests have shown an average of 
0.8 parts of CO per 10,000 of air. In garages the average was 2.1 parts per 10,000 
of air (Bloomfield and Isbell16a). 
Other important industries in which carbon monoxide gas may be a danger 
are those which use gas as a source of heat or power, even natural gas, for though 
it is free from CO, if it burns with too little air, CO will be formed. The produc- 
tion of illuminating gas and of power gas, repair work on pipes, cleaning pipes 
and flues, all are jobs which carry this danger. Less conspicuous are such sources 
as bakeries and hotel kitchens, printing plants, laundries, canneries, pressing 
departments of clothing and of felt hat factories. 
As to the quantity necessary to produce symptoms Haldanelllb put the figure 
at ioo parts per million, and this has been adopted by the American Standards 
Association as the maximum allowable concentration for a daily exposure not 
over 8 hours. For shorter periods, such as occur in the Holland tunnel, Henderson 
and Haggard1113, allowed as much as 400 parts per million, and this is permitted 
also by the American Standards Association for exposure of one hour. The 
studies of Sayers and Yant2753 in garages led them to the same conclusions. Hag- 
gard and Henderson136 offer this rule for the determination of the danger point. 
Multiply the hours by the concentration in parts per 10,000. If the sum is 3, 
there will be no effect; if 6, a slight effect; marked, if 9 and fatal, if 15. Haldane 
showed that the same degree of saturation of the blood with CO would follow one 
hour’s exposure to 400 parts per million, if the man were at rest in a normal 
atmosphere, to 350, if he were at rest in a hot and humid atmosphere and to 250, 
if he were working hard. Age and sex also have their influence. Women seem to 
survive a heavy exposure better than men, probably because men breathe more 
deeply. In experiments with animals, Smith and his colleagues2943 found that 
Vol. IV. 445 CARBON MONOXIDE 
male rats succumb to CO more quickly than females; young rats more quickly 
than old; pregnant females very quickly. 
Acute Poisoning. — Carbon monoxide is not a poison in the strict sense of 
the word. It does not directly injure the cells of the body. Haggard1103 was able 
to grow nerve cells in an atmosphere of 79 per cent. CO and 21 per cent, oxygen. 
Of course the gases used and produced in industry, which we call carbon monoxide 
gas, are often really a mixture. Thus Mayers204b and her colleagues tested the 
effect on red blood corpuscles of pure CO, of automobile exhaust gas and of 
illuminating gas. The first did not increase the fragility of the cells, the second 
did and so did the third, to a much greater degree. Haggard’s nerve cells died in 
an atmosphere of 0.1 per cent, illuminating gas, which contained only 21 per cent. 
CO but also benzol and olefins. The action of carbon monoxide is that of an 
asphyxiant causing anoxemia, and the starvation of the tissues for oxygen is the 
basis of the symptoms, both acute and chronic, and of the sequelae which play 
so important a role in this form of occupational injury. This is the explana- 
tion for the wide variety of lesions which may follow a severe gassing with 
carbon monoxide, depending upon the particular body tissue which has suffered 
damage. 
The asphyxia brought about by CO is caused by the affinity of hemoglobin 
for this gas, which is 300 times as great as its affinity for oxygen, and the resulting 
combination is much more stable. The asphyxia, however, differs from that 
caused by suffocation. Haldane showed that the presence of CO hemoglobin ih 
the blood interferes with the disassociation of the remaining oxyhemoglobin, so 
that a person with anemia of 50 per cent, is better able to utilize the oxygen in 
his blood than is one with a CO saturation of 50 per cent. A third effect is that 
reduced oxyhemoglobin acts as a catalyst in the liberation of carbon dioxide; 
therefore, if there is a loss of oxyhemoglobin by its conversion to CO hemoglobin, 
the removal of CO2 may be hindered (von Oettingen and Associates2423). 
The course of acute CO poisoning was studied by Haldane in a series of self 
experiments which showed that the effects are most marked in the central nervous 
system. After the preliminary symptoms of “mountain sickness”, increasing 
headache, dizziness, confusion, nausea, abdominal pains, he passed into a con- 
dition like that of acute alcoholism, in which his judgment was lost, but he was 
unable to realize that his mind was not as clear as ever. The condition may go 
on to mania. The French have evidently seen many such cases in cooks, for they 
speak of “folie des cuisiniers”, probably caused by the CO from charcoal burning 
stoves. Even if complete coma is not reached, the victim’s power of decision 
and action is so much dulled that he is incapable of saving himself. 
As for the action on the heart Haggard experimenting on dogs saw no direct 
toxic action on the heart, and Drinker’s540 studies of fatal poisoning in man gave 
the same result. In extreme asphyxia the most characteristic effect was heart 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
block. In young, vigorous men there is often low blood pressure and a dilated 
heart, sometimes auricular fibrillation but with recovery usually except in the 
case of the last which is likely to mean a fatal outcome. 
Drinker and Cannon54d found increased moisture in the lungs at autopsy on 
victims of severe poisoning and signs of the same in the lungs of unconscious 
subjects. Almost 10 per cent, of these developed pneumonia (Henderson and 
Haggard136). Chiodi and his colleagues39a found depression of the respiratory 
center in severe CO poisoning and an increase of the cardiac output to as much as 
one half, when saturation is from 30 to 50 per cent. 
Sequelae to Acute Poisoning. — To the physician the most important feature 
of acute gassing by carbon monoxide is the injury, which may have taken place 
during the period of anoxemia, and which may produce temporary or lasting 
symptoms. The literature is full of such instances, and every physician in a steel 
or mining community must have seen at least one such case, yet their number is 
really small in proportion to the acute cases. Engel46, who has had 12 years ex- 
perience in a large steel works, has seen some 1,200 cases of gassing among blast 
furnace men but no sequelae either in the central nervous system or in the lungs 
(also Drinker and Cannon54d and Forbes80a,80b). In the author’s experience lasting 
damage from acute gassing is rare considering the number of men who have been 
gassed, yet some very striking cases have come to light from many different 
sources. 
The studies of Forbes, Cobb and Fremont-Smith80b on man and on animais 
showed that carbon monoxide causes increased congestion of the vessels of the 
brain with edema and a rise in intracranial blood pressure. Given a weakened 
condition of the walls of the smaller vessels, it is easy to see how an acute gassing 
might lead to an apoplexy. Chornyak and Sayers39c made extensive studies on 
animals to determine the neuropathology resulting from rapid CO asphyxia. 
They found severe perivascular and perineuronal edema, most marked in the 
corpus striatum, the cortex, the dorsal motor nucleus of the vagus and the dorsal 
sensory areas of the medulla. In these regions there is extensive damage to the 
neurons. The animals showed decided variation in individual susceptibility. 
According to Hill and Semerak137a the severest damage to the basal ganglia is 
found in victims of gassing who have chronic vascular disease. Skolnick292a de- 
scribes a case in which CO asphyxia acted as a precipitating cause of paresis in a 
syphilitic fireman. That damage to the central nervous system is most marked in 
the corpus striatum was discovered as early as 1865 by Klebs and abundantly 
verified since then (Hill and Semerak137a, Poelchen268b, Grinker104a). Parkinsonism 
is perhaps the most characteristic sequela, but it is not uncommon to find acute 
gassing followed by confusion, amnesia and loss of initiative and of judgment and 
will power lasting for months or for life. 
The nuclei of the cranial nerves are rarely affected, but undoubted cases of 
Vol. IV. 445 CARBON MONOXIDE 
sight impairment, sometimes permanent, have been published (Wilmer33711, 
Murray231a, Brose22c). 
Congestion and edema of the retina and of the disk have been described with 
resulting blurring, dimness, contraction of the visual fields and defective color 
sense. The lesion may be central, in the cortical centers, the optic thalamus, 
the optic tracts. Francois833, found in the literature 2 cases of homonymous 
hemianopsia which followed CO gassing and added one. In his case the left 
field defect cleared up, but the right persisted. Four cases of serious visual de- 
fects following exposure to CO have been reported to the author. Paralysis of 
the external ocular muscles was described by Abelsdorff, nystagmus by Strecker 
and associates302a. 
It must not be forgotten that the most severely gassed victims do not live 
to demonstrate the damage which has been done. 
Drinker and Cannon64d in their survey of hospital records of 21,143 cases of 
acute CO poisoning, mostly non-industrial, found 514 severe cases, unconscious 
on admission. Of these 116 died. Permanent mental or nervous damage was 
shown by only 39 of the 398 survivors, and all of these followed long periods of 
exposure and of unconsciousness. It is rare to see such cases in industry, where 
severe exposure usually is brief. Only in coal mine disasters are workers exposed 
for long periods. That is probably why English authorities consider permanent 
sequelae of CO poisoning characteristic in colliers (Glaister and Logan89a). 
Glycosuria, noted first by Claude Bernard128, is present in practically all severe 
cases, but this action is common to all asphyxiants and is attributed to the in- 
creased supply of adrenin in the blood under the stimulus of the oxygen-lack and 
the increased supply of blood sugar under the stimulus to the liver by the adrenin. 
Usually it appears early and lasts only a short time, 8 to 24 hours, but it may not 
appear till several days after the gassing. That a true diabetes may follow CO 
gassing was asserted by Lewin190a, one of the most authoritative experts in this 
field. Ziesche352*3 reported a typical case in a mason, Rogers264d one in a truck 
driver. 
Other lesions, a wide variety, have been reported from all the industrial 
countries. Polyneuritis (Sanger270*3), choreiform symptoms (Merguet217a), hemi- 
plegia (von Jaksch153b), exophthalmic goitre (Baader9a), injury to the coronary 
vessels (Nagel231*3), increase in blood pressure and basal metabolism lasting 10 
years (Weil325*3), neuritis of the auditory nerve (Alt1*3), skin necroses, gangrene 
(Briggs22*3). 
A very interesting case is reported by Johnstone156, one of severe acute gassing 
followed by deep coma lasting io hours, then complete paralysis of the right side 
with inability to speak. The condition after 3 years showed improvement of 
t'he paralysis but with mental dullness, loss of memory, inability to distinguish his 
wife from other relatives, speech limited to “yes” and “no”. 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Chronic Poisoning. — Chronic CO poisoning still is a field of controversy, for 
although there is generally agreement that it is an actual industrial disease, there 
is little agreement as to the character and the severity of the symptoms, which 
may be caused by long exposure to low concentrations of this gas. It is an ex- 
tremely important subject, for many thousands of workers are exposed in this 
way. That there is no accumulation of CO in the body is beyond question. It 
disappears from the blood, usually within minutes or a few hours; for exceptions 
see Farmer and Crittenden71d. Damage is to be attributed to the cumulative 
effect of repeated doses. 
Is tolerance established, as men in industry believe? Haldanelllb, experi- 
menting on himself and his colleagues, found a certain degree of acclimatization, 
but it disappeared after a short interval. Nasmith and Graham2323 attributed 
this to the temporary polycythemia which they found in animals exposed to CO. 
Killick161a succeeded in acclimatizing mice to such a degree that they flourished in 
an atmosphere which overcame the controls. There was increased blood volume, 
polycythemia with reticulocytes and enlarged spleen. In man he saw increased 
resistance, as much as 34 per cent, increase, but with no demonstrable change in 
the blood. This tolerance disappeared slowly after 18 months. 
The clinical picture is very varied, although no more so than is the picture of 
sequelae following acute poisoning. However, the difficulty in making connec- 
tion between the symptoms and the exposure to CO is great, because there are 
no characteristic signs or symptoms. Even the presence of CO in the blood 
does not prove poisoning, only absorption, although in industrial cases it should 
have great weight, if at the same time the onset of the illness can be shown to 
have followed exposure to this gas. In most cases the complaint is of frequent 
headache, nausea, vomiting, general muscular weakness with increased fatigue 
and “dopiness”. Eurich67a described such symptoms together with depression 
and diplopia in 3 men exposed to exhaust gas from motor cars, and in a fourth 
the symptoms were so severe as to lead at first to a diagnosis of brain tumor. 
Mayers204b in her examination of garage workers heard complaints of insomnia, 
irritability, dizziness, ringing in ears, rapid pulse, rapid breathing, tremors, in- 
creased reflexes, and noted a pallor disproportionate to the degree of anemia, 
vasomotor in origin (also Symanski306a). Loewy192a emphasizes the importance 
as an early symptom of labyrinthine over-excitability shown by dizziness on 
rising in the morning and looking up to the ceiling. Baader9a agrees and holds 
this to be an important diagnostic aid. 
Among the severer manifestations of chronic CO poisoning are the following; 
loss of vision, reduced on the right side to counting figures, on the left to 20/30 
but with narrowing of the visual field (Thompson3153), myocarditis (Ziegler352a), 
pernicious anemia (Berger and Grill121) and Basedow’s disease described by 
several authors as a sequel of acute gassing, by Mahain195b as a result of 2 years’ 
Vol. IV. 445 CARBON MONOXIDE 
exposure in a patient in whom at the beginning of the third year there were tachy- 
cardia, tremor, increased basal metabolism, emaciation but no exophthalmus. 
The most extensive studies of chronic CO poisoning have been made by 
Beck12a,12b together with Sutor. Most of their cases are not industrial in origin, 
but a number are. Beck calls this a neglected clinical problem. In his latest 
publication he discusses his findings in examining 279 persons whose living con- 
ditions were held to involve continuous exposure to CO. He found evidence 
suggestive of chronic poisoning in 137. In discussing his observations on 150 
victims of chronic poisoning he says that most of the symptoms were those 
of simple anoxemia, but that others suggested organic lesions of the central 
nervous system, encephalitis, epilepsy, cerebral thrombosis, multiple sclerosis 
and tetany. Frequently there would be neuromuscular and joint pains, spasms 
of voluntary and involuntary muscles, nausea and vomiting, increase of red 
corpuscles and of hemoglobin. 
On the other hand Rossiter267a denies the possibility of damage by small, re- 
peated doses of CO, since all damage by this gas comes from anoxemia, and low 
concentrations of CO-hemoglobin cannot produce anoxemia. The Public Health 
Service288*5 (Sievers, Edwards and Murray) made a significant report on the effect 
of working many years, 13 years and 4 months, in the Holland tunnel. The study 
covered 156 men working in an atmosphere which averaged 70 per million CO. 
There was no sign of health impairment suggesting occupational disease; the 
response to standard neurological tests was good; there was a low incidence 
of tremors. Blood analysis showed CO-hemoglobin greater in smokers; the 
highest, 13.1 per cent., was in a heavy smoker coming directly from work. Toll 
collectors, whose exposure is greater, went up to 15.1 per cent., but with no 
signs of poisoning. 
Some doubt is thrown upon such findings by the recent experiments of Lewey 
and his colleagues6411’188a designed to test the generally accepted standard of 
ioo parts per million for a working day. This amount in the air leads theoreti- 
cally in man to a concentration of about 16 per cent. CO-hemoglobin, and the 
American Standards Association sets the upper permissible limit at 20 per cent. 
Lewey and associates used dogs exposing them for 11 weeks, 6 days a week, 
hours a day to 100 parts per million of CO. The condition of the dogs ap- 
peared excellent throughout the experiment, but as early as the 2nd week the 
electrocardiograph showed changes which persisted, and at necropsy there were 
signs of degeneration in individual muscle fibres, hemorrhages and necroses in 
the myocardium. Some of the dogs had shown disturbances of gait and of postural 
and position reflexes, and at necropsy there were found histological changes in 
the cortex of the hemispheres and in the globus pallidus of the brain stem, re- 
sembling in type and localization those found after acute poisoning but smaller, 
more scattered and less destructive. 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
These experiments seem to indicate that the accepted standard of 100 per 
million may be too high for man as it is for dogs, and that damage may occur, 
which is too subtle to be revealed by the ordinary physical examination. 
Hydrogen Sulphide 
Hydrogen sulphide, sulphuretted hydrogen, H2S, is a toxic gas which, like 
hydrogen arsenide, has no use in industry, is never deliberately produced, so its 
presence is always the result of some faulty operation or some unexpected re- 
action. It is a colorless gas with an offensive odor, but this is not to be depended 
on, for it occurs at low concentrations, and at high it changes to a not unpleasant 
sweetish odor. Moreover, the gas has a paralyzing action on the nerve of smell, 
and in the author’s experience this effect takes place quickly. It is soluble in water. 
Fortunately the lower explosive limit is at 4.4 per cent, by volume in air, which 
leads to precautions against escape of the gas. 
The possible sources of H2S in industry are many, for it is formed by the de- 
composition of organic matter and, therefore, may be present in the waste pipes 
and sewers draining abattoirs, glue and gelatine factories, fur dressing and felt 
hat factories, tanneries. Sewerage systems are the most notorious sources of 
H2S poisoning. According to- McNally213 it was the sewer gas of Paris which led 
to the first study of H2S in 1777. That gas is said to contain as much as 3 per 
cent of H2S. 
Chemical reactions which give rise to H2S are a part of the production of 
certain dyes and of sulphides and sulphates. The author has histories of several 
cases of severe poisoning from H2S among the pipe fitters, repairers and tank 
cleaners in dye and chemical works. One man, who lifted the lid off a storage 
tank of barium trichloride which stood out in the sun, fell dead. Since the gas is 
soluble in water, it is found in occluded seams in coal mines, formed there by 
the decomposition of pyrites. This is true also of gypsum mines. 01iver244a 
investigated the Sicilian sulphur mines in 1922 and found records of a number of 
deaths from this gas. Other possible sources are in caisson work and in clean- 
ing out the oxide beds in illuminating gas works. 
Recently an unusual source of H2S gas was discovered in the course of digging 
through oolithic limestone in constructing sewer mains in Florida264b. Under- 
ground streams of water were charged with the gas, and when the depth of the 
hole reached 16 feet, a man was overcome, losing consciousness, but rescued 
immediately, he recovered. He had not noticed any odor. Some of the men 
working in shallow holes complained of lassitude, nausea, short breath and con- 
junctivitis. 
Another unusual accident was reported by Nan, Anderson and Cone2310. 
Here there was a mixture of gases, the source being dross containing aluminum, 
Vol. IV. 445 HYDROGEN SULPHIDE 
arsenic, antimony and sulphur. When water was poured on the hot dross, the 
contact with metallic aluminum produced nascent hydrogen which led to the 
formation of AsH3, SbH3 and H2S. 
However, the greatest danger is in oil refineries, where “sour crudes” are 
purified. These come from Mexico and Texas and are rich in sulphur. Yant and 
Fowler350* made a report on the Texas oil fields for the Bureau of Mines in 1926, 
and Aves6b in 1929 described conditions in one of the refineries. In the ten ad- 
joining wells the percentage of H2S ran from 4 per cent, to 14 per cent. All natural 
life has disappeared from these fields, and once a sudden shift of wind drove the 
gas into a corral and killed all the mules. Men have been found lying unconscious 
out in the open to the leeward of a well or in a ravine or near the pumps or tanks. 
Aves notes also that the gas acts on the skin, preventing the healing of cuts and 
scratches unless a gas-tight dressing is applied (also 271a). 
Johnstone156 describes a fatal case in a man who, exposed to a heavy dose of 
H2S in an oil refinery, fell and lay with his face in six inches of water. At autopsy 
no change from normal was noted except the presence of water in the lungs. In 
a second fatal case no organic lesions at all were found. 
The oil industry is the greatest source of severe, accidental H2S poisoning, 
and the viscose rayon industry is the chief source of mild forms from continuous 
exposure. In the latter industry there is a stage at which decomposition of sodium 
tri-thio-carbonate occurs with the formation of sodium carbonate and H2S. 
This is in the spinning department and the gas is evolved in the spinning bath of 
warm sulphuric acid (120). 
Hydrogen sulphide is an irritant to all mucous surfaces and is also an asphyx- 
iant. Haggard111* explains the irritant action as caused by the combination of 
H2$ with the alkali of moist tissue surfaces, forming sodium sulphide which is 
caustic. The asphyxiant action is no longer attributed to a combination of H2S 
with hemoglobin, for as an actual fact that does not happen. H2S combines only 
with methemoglobin, and this occurs in cadavers giving rise to the greenish dis- 
coloration of the vessels of the intestines. Asphyxiation is caused by paralysis of 
respiration, for H2S at first depresses the nervous system, then stimulates it, 
then paralyzes it. Delayed death is from pneumonia or edema of the lungs, 
probably set up by the irritant action on the air passages. The conversion of H2S 
in the blood to the harmless sulphate takes place rapidly so that, if death is not 
prompt, recovery occurs with no lasting damage. 
The fatal dose is between those of carbon monoxide and hydrogen cyanide. 
Concentrations between ioo and 400 per million cause irritation of eyes, nose 
and throat; 500 per million causes, after some 30 minutes, excitement, headache, 
dizziness, staggering gait, diarrhea and dysuria; anything over 500 per million may 
cause severe poisoning, even death. A careful study of the conjunctivitis, which 
is a very common affliction of rayon spinners, has shown that the H2S in the air 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
should be kept down to 20 per million by volume, if inflammation of the eyes is to 
be prevented. The injury to the eyes produced by H2S is described by Bar- 
thelemylla as follows: “intense photophobia, spasm of the lids, excessive tearing, 
intense congestion, pain, blurred vision, the pupils contracted and reacting slug- 
gishly, the cornea hazy, sometimes with blisters on the surface”. Nevertheless 
the acute symptoms usually subside quickly under treatment and removal from 
the poisoned air, but severe cases may result in lasting damage, if corneal ulcers 
occur with scarring. 
The American Standards Association has adopted 20 per million by volume 
as the maximum allowable concentration of H2S. 
A few instances of lasting damage from severe H2S poisoning have been re- 
ported, pneumonia, jaundice, psychic and nervous disturbances (Klein163a). As 
for chronic H2S poisoning there is little information available. From early French 
writings one learns of the “plomb des fosses”, the colic and diarrhea from which 
men working in Paris sewers suffer and which resembles that of plumbism. Dore- 
mus and McNally54 say that workmen in daily contact with this gas develop 
headache, gastric disorder, conjunctivitis and a tendency to furunculosis. Chem- 
ists, who use the gas, often are said to become oversensitive to it, suffering from 
headache, colic, digestive disturbance. But Rodenacker264c thinks such symptoms 
are purely subjective, and Moser229b was unable to produce any effect except some 
irritation of the nasal mucosa in dogs exposed 7 hours daily for 2 months to air 
with 100 per million of H2S. 
Petroleum Distillates 
Petroleum and its distillates, gasoline, benzine, naphtha, petroleum ether, Stod- 
dard solvent, kerosene, are mixtures of hydrocarbons, paraffins, olefins, cyclo- 
paraffins (naphthenes), aromatics, containing also impurities of which sulphur 
is the most important from our point of view. “Straight-run” distillates are pro- 
duced by ordinary distillation, “cracked” by the use of very high temperatures. 
The former consist chiefly of paraffins, but Western oils have the more toxic 
cycloparaffins and olefins and sometimes coal tar benzol and its homologues. 
Cracked gasoline is richer in all these compounds and may carry a fairly high 
percentage of benzol. Lazarew180a tested the toxicity of benzines from different 
sources on white mice and concluded that the difference in toxicity depends on 
the ratio of paraffins to cycloparaffins. The specific gravity to a certain extent is 
a measure of toxicity. 
Not only the composition but the volatility of these distillates determines 
their toxicity in industrial use. The series runs from high test gasoline distilling 
at 65° C. to 150° C. and low test distilling from 150° C. to 2120 C. to solvents, 
naphtha, benzine, petroleum ether, distilling between ioo° C. and 200° C., and 
Vol. IV. 445 PETROLEUM DISTILLATES 
the low-boiling Stoddard solvent used in dry cleaning, which comes off just 
below kerosene. Hydrogenated naphthas are produced from cracked petroleum, 
the object of the hydrogenation being chiefly to reduce the bad odor characteristic 
of cracked products. They are used as solvents for coatings, especially for syn- 
thetic lacquers, and their low volatility makes them much safer than the majority 
of solvents. Solvent naphtha must not be confused with petroleum naphtha, 
for it is a mixture of benzol and its homologues. 
Although these distillates are narcotic poisons, and it is possible to produce 
complete anesthesia with a heavy dose, nevertheless they require so much 
larger a dose than do other industrial solvents, chlorinated hydrocarbons, benzol, 
etc., and the after effects usually are so slight that one is always pleased when one 
finds them in use. Unfortunately they are inflammable and, therefore, are more 
and more yielding to non-inflammables such as carbon tetrachloride, trichlor- 
ethylene, etc. 
No figure has been agreed upon as the maximum allowable concentration for 
gasoline. Some states, Massachusetts and California for instance, have decided 
on 1,000 per million. Machle194 b says that susceptible persons may experience 
discomfort at 300 to 500 ppm. Vigdortschik31913 saw cases of functional neurosis in 
workers exposed to 110-450 ppm. The Bureau of Mines investigators in 1927 
found the odor of benzine detectable at 300 ppm., mild symptoms of narcosis 
beginning in 50 minutes at 1,000 ppm.; by the time 7,000 ppm. was reached, there 
was marked unsteadiness of gait in 10 minutes with numbness of the legs. Philip 
Drinker and his colleagues553, used several groups of normal subjects, men and 
women, and found the latter reacting to a lower concentration than the former. 
Quite tolerable were atmospheres with 270 to 500 ppm. The point at which 
neuromuscular symptoms begin they place at 900 ppm.; mild intoxication begins 
at 2,600 ppm. The vapors are heavier than air. 
The susceptibility of human beings varies very much. The Russians2773 hold 
that the obese are oversusceptible and that a fatty diet encourages poisoning. 
Machle has seen refinery workers develop resistance to the fumes, and Lazarew 
and his colleagues18013 produced a marked degree of tolerance to benzine fumes, 
which they attribute to the animals’ loss of fat, for the action of benzine is on 
the lipoids. 
The industries in which gasoline fumes constitute a hazard are the refineries 
and the users of solvents, a long list of which is to be found on another page of 
this chapter. There are many other sources of possible danger in refining pe- 
troleum, chiefly the gases that may be given off in the course of distillation, such 
as hydrogen sulphide, carbon monoxide, sulphur dioxide, ammonia, chlorine. 
A complicated clinical picture may be produced by a mixture of one or more of 
these with gasoline. 
Acute Intoxication.— The symptoms are those of a narcotic poison with 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
nothing especially characteristic. Workers call such an attack a “naphtha jag”. 
There is fullness in the head, headache, blurred vision, dizziness, unsteady gait, 
nausea, etc. and a typical “morning after”. Yet, as is true of alcoholic intoxi- 
cation, the experience may be enjoyed. On the other hand, some workers become 
very irritable and quarrelsome. A foreman in a rubber spreading department 
told the author he always was careful how he spoke to his men toward the end 
of the day. A group of painters using cheap, quick-drying paint in small rooms 
complained of what they supposed was lead poisoning, nausea, pain in the navel 
region, smarting eyes, spots before the eyes, dimness of vision, headache, dizzi- 
ness. In some cases these symptoms came on first when the man went out into 
the open air. The paint proved to be lead-free but with benzine and turpentine 
as the carrier. 
Moorman227a has noted this fact, which is well known to men in the industry, 
that the symptoms often increase when the victim reaches the open air. Several 
such instances were reported to the author. One was that of a rubber worker, 
who dipped glove forms in a tank of rubber dissolved in naphtha. He felt sick 
and dizzy and started to go home, but on the way he began to stagger and had to 
be half carried to the house; not till he was in bed did he lose consciousness. 
Massive doses such as occur only through an accident result in sudden collapse, 
coma, sometimes death. An interesting case was described by Plummer258a of 
acute gasoline poisoning in a lad of 16 years who was cleaning a storage pit in a 
garage. Found dazed in the pit, he was carried outside when he vomited violently, 
became delirious and lapsed into coma, which lasted 3 hours, with shallow breath- 
ing, weak, thready pulse, contracted pupils and inward strabismus. He made a 
complete recovery. 
In fatal cases no characteristic morbid changes are found; usually the blood 
vessels of the organs show damage, small hemorrhages; there is bronchitis, edema 
of the lungs, in a case of Johnstone’s extensive pleural effusion, but the changes 
in the central nervous system are not marked. Briganti and Ambrosio22a, ex- 
posing rabbits to heavy concentrations of low-boiling benzine, found extensive 
hemorrhagic areas and cell injury in kidneys, liver and adrenals, increased blood 
cell destruction in the spleen and hyperplasia of lymph follicles in spleen and 
intestinal tract. 
Hemorrhages in the lungs were the most important feature in 2 cases of severe 
acute poisoning described by Jaffe152a, and he was able to reproduce this condition 
in animal experiments. 
Chronic Intoxication. — As is true of all the industrial poisons, the study of 
acute forms is not nearly so important as the study of chronic forms and of pos- 
sible sequelae of the acute. Some striking instances of the latter are reported 
in German literature. 
Floret79a of the Chemical and Dye Works at Elberfeld described 2 unusual 
Vol. IV. 445 PETROLEUM DISTILLATES 
cases. One was in a young girl, who suffered from epileptiform convulsions for a 
year after an acute poisoning from benzine fumes. The other was in a man, who, 
while filling cans with benzine, lost consciousness and, when he came to, complained 
of pains in neck and head. There was great restlessness, stiffness of the neck as in 
meningitis, high fever and albuminuria. After a few days an erysipeloid eruption 
appeared over the buttocks, later becoming necrotic, and similar areas appeared 
in mouth and throat. Floret believes these were caused by the excretion of 
benzine through the skin. The man died in the fifth week after the accident. 
Stiefler301a describes a case of epilepsy occurring in a man 21 years of age. He 
had been emptying a can of benzine, fell unconscious and was taken to a hospital. 
The following symptoms in addition to unconsciousness were noted; asphyxia, 
tonic muscle spasms especially of the arms, vomiting and dyspnea. He recov- 
ered and was discharged in 10 days. Three or four months later he had his first 
attack of epilepsy. The attacks were repeated every 4 or 5 months and were 
typically epileptic. Examination revealed no clinical evidences of organic changes 
in the nervous system or other organs. The author believes that the benzine 
so changed the brain as to render it a suitable soil for epilepsy. 
The most famous cases of chronic poisoning in the literature are those of 
Dorendorff64a and of Haden108b. The first described the nervous symptoms in 
4 men engaged in rubber manufacture, who suffered from lancinating pains in 
the limbs, coldness and numbness in the hands, loss of strength, loss of memory 
and in one case, difficult speech. Haden’s patient was a man, who for 13 months 
had cleaned lithograph rolls in a trough of benzine using 2 gallons a day, all of 
which evaporated in a room with no ventilation. He began to suffer the symptoms 
typical of a narcotic poison after 2 months, and his weakness increased till he took 
an hour to walk home instead of 15 minutes. He was so drowsy he had to wash 
his face in cold water to keep awake; his legs felt heavy and cold; he had painful 
muscular cramps in the arms, and his vision was dimmed. After 13 months had 
passed, his mentality was dull and confused, his reflexes active; there were 
tremors of eyelids and tongue. A very unusual feature was the involvement 
of the liver, jaundiced skin, enlarged and tender liver, urine almost black with 
bile coloring matter. He improved rapidly under treatment and removal from 
benzine. 
Dorner’s54b case also belongs in the very small list of reported cases of lasting 
damage after acute intoxication. This was the result of an accident, a fall into 
a tank of crude benzine. The man lay for 20 minutes half immersed in the fluid. 
Dorner saw him 7 months later with motor paralysis of the legs, which Dorner 
traced to degeneration of the pyramidal tracts. 
Kraus’173a case, one of motor and sensory paralysis with marked atrophy of 
all the limbs, was in a garage worker exposed to both gasoline and CO fumes 
Kraus does not attempt to decide what part each played. 
VOL. IV. 445 INDUSTRIAL TOXICOLOGY: PATHOLOGY: DIAGNOSIS 
Chronic benzine poisoning is considered by some experienced men as fairly 
common among industrial workers, but others think it is very rare. Of course 
there are wide differences in the conditions under which the work is done, so the 
results of different surveys may not be comparable. The action of benzine is 
primarily on the central nervous system, and the symptoms are those of a nar- 
cotic poison. Hayhurst130a examined a group of workers constantly exposed to 
benzine and lists the following symptoms; headache, dizziness, loss of appetite, 
dyspepsia, insomnia, nervousness, pains in back, legs and heart region, weakness 
and dyspnea. These symptoms made their appearance after 3 weeks to several 
years of exposure. There were also objective signs, loss of weight from 10 to 50 
per cent., tachycardia, secondary anemia with leucocytosis, mental depression, 
stupor, twitchings and tremors. 
Quadland262b describes a case in a man, who for 13 months dipped shingles in 
a stain the solvent of which was benzine, § kerosene. He complained of diarrhea, 
gastric upset, attacks of numbness, vertigo, weakness, and he had lost weight as 
much as 40 pounds. Later he developed cardiac disturbances, paresthesias and 
“syncopal attacks”. Quadland’s second case, in a woman, was one of extreme 
emaciation, a fall in weight from 158 lbs. to 65, extreme nervousness, mentality 
impaired. The third, a man working with high-test gasoline, had also lost weight, 
suffered from marked nervousness and in addition had bleeding from nose and 
gums. 
This last manifestation of chronic benzine poisoning, hemorrhagic tendency, 
comes into the picture in other reports. Koelsch166a describes a case of bleeding 
from the lungs together with albuminuria and anemia. The most remarkable 
instances are those described by Smithies298a, partly in a personal communication 
to the author, where the exposure to “very volatile oil distillates” resulted in 
several instances not only in hemorrhages but in laking of the red corpuscles. In 
one of the cases xylol was involved as well as benzine. 
The effect of chronic benzine poisoning on the blood still is a matter of con- 
troversy. The earlier literature, especially the French and Italian, contains 
descriptions of aplastic anemia indistinguishable from that caused by benzol 
in persons exposed to petroleum benzine, but these are open to the suspicion that 
the solvent used was not pure benzine, that benzol was present also. Animal 
experiments for the most part do not reveal marked changes in the blood (La- 
zarew180a). On the other hand Petrini255a, also on the ground of animal experi- 
ments, says that the effect of gasoline fumes on the blood differs from that of 
benzol only in degree. 
Machle194b, who has had some 2,300 refinery workers under observation for 
10 or 12 years, believes that chronic benzine poisoning is very rare. Only among 
the barrel fillers, who are more heavily exposed, did he find suggestive symptoms, 
pallor, low red cell count and low hemoglobin, anorexia, nausea, nervousness. 
Vol. IV. 445 PETROLEUM DISTILLATES 
These symptoms were clearly connected with the men’s work. The history of 
exposure is of great importance in making a diagnosis, for no laboratory tests 
are significant. Moorman227a also considers the danger of chronic poisoning slight. 
Spencer300a in a study of the dispensary attendance of a group of workers 
exposed to gasoline fumes in cleaning rubber belts found that such exposure in- 
creased the numbers seeking dispensary service and reduced the output of the 
workers. He describes the usual nervous symptoms, also distaste for food, con- 
stipation, loss of weight and of strength, pallor, twitching muscles. A change 
to a good grade of high-boiling kerosene helped decidedly. 
Lubricants and cutting oils are mixtures, which usually contain the heavier 
petroleum distillates, the so-called mineral oils. These are a prolific source of 
skin lesions from acne to furunculosis. Various causes are given for this action, 
the plugging of sebaceous ducts by the oil, the presence in the oil mixture of 
irritating substances such as hydrocarbon sulphonates or unsaturated hydro- 
carbons, assisted by the overuse of abrasive soaps, which remove the surface 
cells of the skin and also the natural oils of the skin. Since cutting oil is used over 
and over again, it gets dirty and may become heavily contaminated with pus- 
forming bacteria. Staphylococcus aureus has been isolated from such oils and 
has been known to start an epidemic of skin boils (Shie287a). 
Finally, brief mention must be made of the fact that certain industrial oils 
contain carcinogenic substances. The most notorious is the Scottish shale oil, 
which was discovered to be the cause of scrotal cancer in mule spinners in the 
textile centers of England. These cases began to appear some years after mineral 
oil was substituted for animal and vegetable oils. American oils are compara- 
tively free from these substances. Pennsylvania oils seem to be quite free, but 
mid-Continent oils are not, and cases of epithelioma have occurred in plants where 
such oils are refined (Heller135b). 
Vol. IV. 445 Part II 
TREATMENT AND PREVENTION 
RUTHERFORD T. JOHNSTONE 
Foreword 
Probably no illness is so needless or so inexcusable as that which arises from 
occupation. Except for the unforeseen accident such as a sudden, unavoidable 
escape of gas, for instance, practically all noxious substances can be controlled 
and the workmen guarded. Typhoid, once a scourge to the civilian population, 
is now of negligible incidence owing to good hygiene. Just so, many noxious sub- 
stances of industrial origin, which once caused widespread illness or death, now 
are well controlled. Industrial management to a great extent has cleaned house 
and now observes good housekeeping. Maintenance of this desired state is the 
responsibility of the industrial engineer and hygienist. 
It is obvious, then, that the prevention of the occupational diseases should 
be the goal of industrial medicine. Inability to eradicate completely occupational 
ill health arises from the constant introduction of new substances with which man- 
agement and the medical profession are not familiar or the failure of small plants 
to maintain a program of medical supervision or hygiene. Such being the case, 
the occupational diseases will continue to occur. 
Treatment will be adequate, however, if the physician adheres to the two fol- 
lowing precepts: 
(1) Determine as quickly and as accurately as possible the occupational 
cause. In general practice a sore throat may yield to aspirin or a gargle, but 
such treatment would hardly be sufficient, if it were a case of diphtheria. In in- 
dustry salve usually is satisfactory for a chemical burn, but inadequate if the 
burn is due to butadiene. When confronted with an industrial emergency, it is 
always good practice to get in touch with the responsible man at the plant, where 
the illness occurred, in order to ascertain the exact nature of the exposure. This 
simple advice too frequently is neglected. 
(2) In only rare instances is the treatment of occupational diseases specific. 
Rather, treatment is usually a regime directed toward restoration of the function 
of one or more of the systems of the body. The space allotted does not permit 
consideration of every noxious substance to which a workman may be exposed, but 
a few general axioms will serve to guide in the general treatment: 
COPYRIGHT 1944 BY THE OXFORD UNIVERSITY PRESS, NEW YORK, INC. 
Those portions of the body most likely to be affected by an industrial sub- SULPHUR DIOXIDE 
stance, especially that large group known as the solvents, are (a) the nervous 
system, (b) the hemapoietic system, (c) the kidneys and (d) occasionally the 
liver. There are exceptions to this rule, but they are rare. 
An acute exposure to a substance may affect one system of the body, whereas 
a slow, chronic exposure to that same substance may affect an entirely different 
system. A further consideration of the selective action of the industrial chemicals 
introduces these observations: 
(1) The disturbance to the central nervous system by the solvents is due 
largely to the property that resides within them of dissolving fats. Thus, they 
may act upon the lipoid substance in the nerve fibres or myelin sheaths or upon 
the cytoplasm. Their anesthetic action also depends on this fat-solvent prop- 
erty, an action similar to that of chloroform, cyclopropane or acetylene. If the 
exposure exceeds a mild stage, then narcotic effects are produced, even sometimes 
to the point of sudden death. 
(2) Certain solutions or gases manifest a strong affinity for the hemoglobin 
of the blood or cause alteration or destruction of the blood cells. An exposure to 
arsine, hydrogen cyanide, carbon monoxide or nitrogen dioxide may be acutely 
fatal. Slow, prolonged exposure to certain chemicals, such as benzol, may result 
in anemia of inconstant type. 
(3) In excreting certain of the toxic chemicals the kidneys may be damaged. 
This is quite often a delayed reaction as in carbon tetrachloride poisoning. 
(4) Also the liver in metabolizing and detoxifying certain of these noxious 
substances may be affected by constant, repeated assault. The chief chemical 
offenders are the chlorinated naphthalenes, carbon tetrachloride, trinitrotoluene, 
and one or two others. 
These foregoing observations rightly belong under the discussion of diagnosis 
but have been made here to serve as sign posts for treatment. 
Sulphur Dioxide 
Irritation of Eyes. — Workers in industrial plants, firemen or refrigerator 
men, who are apt to encounter this gas, should wear gas masks. Treatment of an 
eye injured by this gas is similar to that of the eye injured by ammonia. Copious 
laving of the eye with water followed by the introduction of saturated solution 
of boric acid and by the use of a local anesthetic such as 0.5 per cent, pontocaine 
hydrochloride is indicated. These are followed by the application of olive oil 
or some similar oil. Corneal ulceration should be watched for carefully and 
treated appropriately, if it occurs. 
Respiratory Disturbances. — For those overcome by the gas inhalations of 
from 5 to 7 per cent, carbon dioxide in oxygen are to be used over a long or short 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: TREATMENT 
period, depending on the severity of the case and the individual patient’s reaction. 
If pulmonary edema is present, oxygen alone should be used. In very severe cases 
artificial respiration is to be employed coincidentally with the inhalations. In 
some cases the use of respiratory and circulatory stimulants such as coramine, 
metrazol and caffeine sodium benzoate may be of value. A few days of absolute 
bed rest should be advised for those who have had a fairly severe exposure, and 
this should be continued until all evidence of respiratory embarrassment ceases. 
During this period codeine phosphate or sulphate gr. \ to 1 (30 to 60 mgm.), every 
four to six hours, will alleviate the cough and may be combined frequently to 
advantage with a soothing cough syrup mixture. Bland oils should be applied to 
the exposed membranes. For those who display symptoms of acute asthma the 
subcutaneous administration of \ to 1 c.c. of 1:1,000 solution of epinephrine may 
relieve the symptoms. The use of a nebulizer for inhalation of 1:100 epinephrine 
might be of value also. 
In very severe cases pulmonary edema requiring venesection could conceivably 
occur, although we have not seen such an instance. In such a case acidosis and 
intense air hunger may accompany the anoxemia. Treatment of the acidosis, if 
present, should follow the suggested outline given under Methyl Alcohol. Some 
authors feel that the severely ill patient should not even be asked to move in bed, 
since any slight exertion may cause the failure of an overworked and asphyxiated 
heart. 
Chlorine 
War Use versus Industrial Use. — The author has had experience with two 
sources of chlorine gassing, one while in World War I and the other from industry. 
In the first instance the victims were affected more severely because usually they 
could not withdraw from the hazard. In industry there occur but few severe 
exposures. Men are warned of the presence of this gas and immediately with' 
draw. If severe affection occurs, treatment should be directed to the respiratory 
tract in order to relieve the irritation and congestion. 
Immediate Measures. — The patient severely gassed with chlorine should be 
removed from the toxic atmosphere promptly, and all constricting clothing about 
the neck should be loosened. He should be kept quiet in a recumbent position 
and should be wrapped with warm blankets while hot water bottles are applied. 
Oxygen should be administered in all cases. It is considered best not to wait for 
cyanosis to develop, since the administration of oxygen often will prevent cyanosis 
and relieve the pain of deep inspiratory effort. Venesection of from 400 to 600 
c.c. is an extremely valuable measure and should be performed early on all patients 
who have been exposed to heavy concentrations, but, as already indicated, such 
exposures in industry will be very rare. The early use of such phlebotomy often 
Vol. IV. 944 FLUORINE 
prevents development of edema of the lungs, and if used later, often relieves pul- 
monary edema and cardiac embarrassment. The early intravenous administra- 
tion of 10 per cent, dextrose in physiological solution of sodium chloride may be 
combined with venesection to combat shock and reduce viscosity of the blood. 
As with phosgene poisoning venesection is contraindicated, if the gray stage of 
anoxemia with pallor, collapse and rapid, thready pulse has been reached. • 
Relief of Pain and Excitement. — Morphine sulphate is not to be used, if 
pulmonary edema and respiratory embarrassment have ensued. Some advise, 
however, its use for relief of pain and excitement soon after injury. Atropine, 
epinephrine, digitalis and strychnine are not of much benefit. Caffeine sodium 
benzoate, gr. (0.5 gm.) or 1 to 2 c.c. of camphor in oil given intramuscularly 
sometimes produces beneficial results. 
Complications. — If pneumonia is a complication, oxygen therapy is con- 
tinued. If a specific infection superimposed upon the injured lung is demon- 
strated, the use of the appropriate therapeutic agents, e.g., sulfanilamide, sulfa- 
pyridine, sulfathiazole or serum, are advised. 
Olive oil in the eyes may be effective. Codeine phosphate or sulphate, gr. 
to 1 (30 to 60 mgm.), for cough or spraying of the nose and throat with a sooth- 
ing solution at times is useful, but for this latter use products containing oil should 
be avoided because of the danger of developing a lipoid pneumonia. The patient 
should be reassured regarding any permanent effects to the lungs. A neurosis 
may be avoided by the initial attitude of the physician and malingering obviated 
by the emphatic imparting of existing statistics and knowledge regarding these 
cases. 
Fluorine 
Combating Calcium Deprivation. — Since the mechanism of fluorine toxicity 
consists of a calcium deprivation, treatment should be designed primarily to cor- 
rect this and thus render the fluorine inert. In the acute case of poisoning gastric 
lavage with lime water or a weak solution of calcium chloride together with from 
10 to 20 c.c. of 10 per cent, calcium gluconate intravenously from one to three 
times a day should be used. 
Respiratory and Circulatory Complications. — If cyanosis is present, the ad- 
ministration of oxygen by an intranasal tube or by a tent is indicated, and respira- 
tory stimulants may be needed, such as i to 2 c.c. camphor in oil intramuscularly, 
7 per cent, carbon dioxide in oxygen as an inhalation, 1.5 c.c. coramine intramus- 
cularly or intravenously, or gr. i\ to (0.1 to 0.3 gm.) metrazol intramuscu- 
larly or intravenously. The latter two or epinephrine, 1 c.c. of a 1:1,000 solution, 
intramuscularly are indicated for circulatory failure. 
Shock. — The use of 1,000 c.c. of io per cent, dextrose in saline given slowly 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PREVENTION 
intravenously will be of value in combating shock, particularly if pulmonary 
edema is absent. The patient is, of course, kept warm with blankets and hot 
water bottles. 
Sedatives in Complications. — Codeine phosphate or sulphate, gr. to 1 
(30 to 60 mgm.), repeated every four to six hours, at times is needed to allay 
violent coughing. The codeine may be given in any of a number of soothing cough 
syrups. Dilaudid hydrochloride, gr. 1/32 to 1/16 (2 to 4 mgm.) given hypo- 
dermically or by mouth, may help also in this regard, as do morphine sulphate, 
gr. i to (10 to 15 mgm.) or pantopon, gr. to J (10 to 15 mgm.). These seda- 
tives and one of the barbiturates may be needed to control convulsive seizures. 
Bronchial Asthma. — If symptoms of bronchial asthma appear, the use of one 
of the following is indicated; ephedrine sulphate, gr. f (24 mgm.), given every 
four to six hours, neosynephrin, 0.25 to 0.5 per cent, solution used in a nebulizer, 
aminophyllin, gr. (0.1 gm.), every four to six hours, or gr. (0.5 gm.) in 
20 c.c. of distilled water, given intravenously slowly over a five-minute period or 
epinephrine, \ to 1 c.c. of 1:1,000 solution hypodermically or as inhalations of a 
1:1,000 solution from a nebulizer. 
Obstipation and constipation may need attention, and if vomiting is severe, 
the further administration of from 5 to 10 per cent, dextrose in physiological 
saline solution, 1,000 to 3,000 c.c. daily, is to be used. No established treatment 
exists for stiffness of the body due to bony and ligamentous changes, but it appears 
that on gradual elimination of the fluorine considerable reduction takes place in 
osseous overgrowth. 
Treatment of Burns. — It is suggested that the burns be treated as described 
by Jones. The burned area is washed thoroughly with, or immersed in, a warm 
saturated solution of sodium bicarbonate. Then an ointment prepared by thor- 
ough mixing of two parts medical paraffin or glycerin with one part of magnesium 
oxide is massaged into the burned area, and a dressing of the same ointment is 
applied; 2 c.c. of sterile 10 per cent, calcium gluconate solution is injected into, 
and under, all areas showing whitened skin. The magnesium oxide ointment 
dressing is renewed night and morning for five or six days. After this period 
boroseptic ointment is an efficient and soothing application, and healing can be 
completed by dressing with ichthyol ointment. The eyes, if involved, should be 
irrigated for at least an hour with normal saline solution, and then the ointment 
described above should be applied. 
Nitrous Fumes 
Correction of Pulmonary Effects. — Oxygen, which has been passed through 
a bottle containing 2 gm. ammonium carbonate to 1.5 ounces of water, should be 
Vol. IV. 944 WELDING 
administered to patients in acute cases by means of an intranasal tube. McNally 
recommends a tube in each nostril. For relief of the pulmonary edema intra- 
venous 50 per cent, dextrose in amounts of from 50 to 100 c.c. up to 200 c.c. daily 
should be used; salyrgan, 0.5 to 2 c.c. intravenously at intervals of three days is 
also of much value in treating the pulmonary edema. Sedation for restlessness 
will be needed in many cases. 
If pneumonia appears as a complication, the use of chemotherapy, i.e., sul- 
fanilamide, sulfapyridine, sulfathiazole or serum, may be instituted, if a predomi- 
nant organism can be demonstrated in the sputum. In case the carbon dioxide 
combining power is low, the treatment should be that described for acidosis under 
Methyl Alcohol. 
Chronic Exposure. — Persons affected by chronic exposure may be benefited 
also by intravenous salyrgan. It is said that these patients often find sleeping 
in a rocking chair easier than in bed. Frequently they will need acetylsalicylic 
acid or phenacetin, gr. 10 (0.6 gm.), every four to six hours, for the headache, 
or if this symptom is more severe, codeine sulphate or phosphate, gr. \ to 1 (30 
to 60 mgm.) every four to six hours. Sedation with drugs such as sodium bro- 
mide, gr. 10 to 30 (0.6 to 2 gm.), phenobarbital, gr. (0.1 gm.) or sodium 
pentobarbital, gr. (0.1 gm.), three times a day, is needed at times for rest- 
lessness. Constipation may need attention. The mouth washes described under 
Mercury may be of benefit in ulcers of the mucous membranes. The addition 
of extra vitamins to the diet should be of value. 
Welding 
Prophylaxis. — Preventive measures include protection of the eyes from 
flashes, glare and radiant energy, respirators for protection against inhalation 
and protective coverings of the exposed parts of the body. Indoor welding should 
be done where the walls are painted black to reduce the reflection, or booths 
should be provided. Outdoor welding should be done in portable canvas booths. 
The treatment of metal fume fever and nitrogen peroxide, lead, carbon monox- 
ide or cadmium poisoning, when they occur as a result of welding, is indicated 
under those headings. 
Electric Ophthalmia. -— When this occurs, a superficial injury to the corneal 
epithelium with exposure of superficial nerve terminals will have occurred. The 
pain frequently is very severe and may require one of the following for relief; 
morphine sulphate, gr. \ (15 mgm.), dilaudid hydrochloride, gr. 1/16 (4 mgm.) 
or pantopon, gr. £ (20 mgm.). Both eyes should be bandaged completely, and 
locally anesthetic ophthalmic ointments, e.g., 2 per cent, holocaine hydrochloride, 
2 per cent, butyn or 4 per cent, metycaine, are to be used. 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: TREATMENT 
Gases from Carbon Arcs 
The chief hazard here, when it does occur, is from the oxides of nitrogen. The 
prevention and treatment of such poisoning have been discussed under Nitrous 
Fumes. 
Prophylaxis. — The important point here again is prevention. The major 
portion of such prevention consists of adequate ventilation. It has been sug- 
gested that each projector lamp should be connected to a flue in which fumes from 
arc combustion are exhausted by means of motor driven fans to the out of doors. 
This fan should turn on automatically as the arc is struck, and the exhaust should 
run at a minimum of 12 cubic feet a minute with a rate nearer 100 being preferable. 
Ammonia 
General Measures. — If liquid ammonia is spilled upon the clothing, all cloth- 
ing should be removed immediately and the body thoroughly drenched with 
water. The eye injured by ammonia should be washed immediately and copi- 
ously with water, and this may be followed by the introduction of a saturated 
solution of boric acid. If pain is severe, the use of a local anesthetic such as 0.5 
per cent, solution of pontocaine hydrochloride is indicated. Thereafter the appli- 
cation of olive oil or some similar oil is desirable. Continuous warm boric com- 
presses to the eyes may be of value. The usual treatment for corneal ulcers 
should be instituted, if this complication occurs, and an ophthalmologist should 
be consulted. 
Respiratory and Circulatory Measures.—If the concentration of fumes has 
been severe and respiration affected, inhalations of from 5 to 7 per cent, carbon 
dioxide in oxygen should be given, and if pulmonary edema ensues, the use of 
oxygen by means of a tent or intranasal apparatus is advised. The administra- 
tion of such respiratory and cardiac stimulants as the following may be of value; 
coramine, 1.5 c.c., metrazol, gr. i-| to \\ (0.1 to 0.3 gm.) and caffeine sodium 
benzoate, gr. (0.5 gm.). Some of the respiratory and cardiac effects may be 
reflex in origin from the pulmonary bed, and because of this, the intravenous ad- 
ministration of atropine sulphate, gr. 1/75 to 1/60 (0.9 to 1.0 mgm.) and pap- 
averine hydrochloride, gr. \ (30 mgm.), might be of value. These should be pre- 
pared freshly from the powders just before use. 
Mercury 
Acute Poisoning. — This is usually the result of intentional or erroneous in- 
gestion of the bichloride of mercury and so will not be seen frequently in industry. 
Vol. IV. 944 MERCURY 
However, as indicated by the cases reported by Williams and Schram336, severe 
exposure may result in symptoms primarily involving the gastrointestinal tract. 
Gastrointestinal Involvement. — In such cases gastric lavage is indicated at 
once. A number of chemicals have been used with the wash water to precipitate 
the mercury and to delay its absorption. The most promising agent so far seems 
to be sodium formaldehyde sulphoxylate. The chief difficulty is that its effect is 
not great, if as long as fifteen or thirty minutes elapse before it is given. A freshly 
prepared solution of 10 per cent, of the sulphoxylate with 5 per cent, of sodium 
bicarbonate is to be used for the gastric layage, and about 200 c.c. of the mixture 
is left in the stomach. An intravenous injection of from 10 to 20 gm. of sulphoxy- 
late in a 10 per cent, solution should be given also over a period of from 20 to 
30 minutes. 
Its use except in the acute case seen quite early is open to question, since there 
is some experimental evidence demonstrating that, while sodium formaldehyde 
sulphoxylate is of value in the prevention of the manifestations of poisoning, it 
actually may aggravate preexisting intoxication. Monte and Hull226 felt that its 
repeated use was inadvisable and strongly doubted its efficacy in any instance. 
It is probable that acute mercury poisoning will be seen earlier in industrial than 
in private practice, and hence the therapy outlined may be of considerable value. 
Lavage with three tablespoonfuls of charcoal and 20 gm. of magnesium sulphate 
to a pint of water has been advised by McNally213. One gram of charcoal binds 
180 mgm. of bichloride of mercury. Following this lavage two eggs in water and 
a glass of milk are to be administered. This is followed by another lavage with 
water, and finally four tablespoonfuls of charcoal are given by mouth, not to be 
removed. The milk, which is used, should have the cream removed, since fats 
dissolve mercury salts more quickly and aid in the absorption. 
Pain and Prevention of Shock. — In these conditions morphine sulphate, gr. 
\ (15 mgm.), every four to six hours, is recommended. For further treatment 
in shock caffeine sodium benzoate, gr. (0.5 gm.) or epinephrine, 1 c.c. of 
1:1,000 solution, may be given hypodermically, and an intravenous infusion of 
10 per cent, dextrose in saline (1,000 c.c.) is indicated. 
Subsequent Treatment. — Various therapies have been outlined for the sub- 
sequent treatment of the patient. Good results have been claimed for the intra- 
venous use of sodium thiosulphate, gr. 15 (1 gm.) in 10 c.c. water, from one to 
six times daily, for from three to five days. Hashinger and Simon129 reported a 
patient treated chiefly by exsanguination-transfusion with complete recovery. 
Koranyi172 reported complete recovery of a patient with beginning oliguria, 
hematuria and albuminuria by the use of daily venesection (300 c.c.), daily oral 
administration of 5,000 c.c. Ringer’s solution and the intravenous administration 
of 20 c.c. of a 10 per cent, solution of sodium chloride. Others have advised 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PREVENTION 
multiple transfusions of from 300 to 350 c.c. Cecostomy has been used with 
good results. 
It is very important that the lowered blood chloride level should be treated 
by intravenous administration of physiological saline, and that acidosis be treated 
as described under Methyl Alcohol. Sodium citrate or acetate in amounts suffi- 
cient to keep the urine alkaline is to be given by mouth. 
A regimen consisting of 250 c.c. of the following mixture has been used at 
hourly intervals: potassium bitartrate, 1 drachm (4 gm.), sugar, 1 drachm (4 
gm.), lactose, \ ounce (15 gm.), lemon juice, 1 ounce (30 c.c.), boiled water, 
16 ounces (500 c.c.) along with 250 c.c. of milk. In combination with gastric 
lavage with 6 quarts of sodium bicarbonate solution and colon irrigation twice 
daily, daily sweating in a hot pack and continuous rectal irrigation with a solu- 
tion of potassium acetate, a drachm to the pint, this treatment has given some 
good results. 
For muscular twitchings of uremia, calcium gluconate, 10 c.c. of a 10 per 
cent, solution intravenously, is of value. 
Chronic Poisoning. — No treatment of demonstrated value in chronic poison- 
ing has been reported. Removal from the hazard is, of course, absolutely essen- 
tial. The use of sodium thiosulphate might be of value, gr. 15 (1 gm.) in 10 c.c. 
of sterile water intravenously every other day for a short time. 
Nervous Disorders. — Most of the treatment in the chronic case is directed 
toward alleviation of the nervous affections. Since many of these patients have 
symptoms similar to those seen with chronic encephalitic Parkinsonism, it has 
been suggested that a trial of drugs used in that disease be made. The older 
drugs of this group are scopolamine hydrobromide (hyoscine), gr. 1/200 to 1/100 
(0.3 to 0.6 mgm.), two or three times a day, or tincture of stramonium, 60 to 90 
minims three times daily. 
A drug used more recently is amphetamine sulphate or benzedrine sulphate, 
20 to 30 mgm. twice daily at 8 a.m. and at noon, in conjunction with a drug of 
the atropine group or genoscopolamine, in dosage of 0.5 mgm. granules, one three 
times per day, increasing the dosage after several days to two or three granules 
three times a day. The latter is said to have far less toxic effects than atropine, 
hvoscine and stramonium. 
Stomatitis. — For this the following mouth washes may be used; tincture of 
myrrh, i part to from 25 to 50 parts of water, potassium permanganate, 1:8,000 
or 2 ounces (64 c.c.) of each thymol, hydrogen dioxide and glycerin with sat- 
urated solution of potassium chlorate sufficient to make 8 ounces (250 c.c.). 
Good oral hygiene is imperative. A diet high in vitamins with the vitamin 
B complex particularly added should be of value. Diarrhea or constipation, if 
present, should be controlled. 
Vol. IV. 944 MANGANESE 
Manganese 
Prophylaxis. — The prevalence of this disease can be limited by engineering 
control. Isolating the process under hoods or exhaust ventilation, control of the 
dust by wet processes, the use of mechanical conveyors and examination of the 
atmosphere at intervals, all are preventive measures. Jones observed no cases 
of intoxication among men working in an atmosphere of less than 30 mgm. of 
manganese per cubic meter of air. He states that this should not be considered 
a threshold limit and suggests an atmosphere of 50 mgm. per 10 cubic meters as 
a maximum. Quarterly medical examinations should be routine in any mill or 
place where manganese compounds are handled in order to detect early signs or 
symptoms. Mild neurological signs or symptoms such as drowsiness, languor, 
muscular cramps and twitching, perhaps coupled with an otherwise unaccountable 
low white cell count, indicate removal of the workman from the hazard. Daily 
showers following work should be encouraged by installation of shower baths and 
education of the employee in this regard. 
Nothing of real value in the treatment of these patients has been described. 
For those mildly affected much improvement, perhaps total, will occur on their 
removal from the exposure. For those severely affected little improvement may 
be expected. 
Vitamin Bx and Calcium. — Well-rounded, adequate diets should be given 
these patients, and general tonics may be used. There is some question concern- 
ing the use of thiamine hydrochloride, vitamin B,, since experimentally large 
doses of vitamin B, encourage retention of manganese, and hence Bj might be 
contraindicated here. Since low blood calcium levels have been demonstrated by 
some, oral calcium preparations and milk may well be included in the diet. The 
patient should be encouraged to drink adequate amounts of fluids and should be 
given cathartics, if necessary, in order to secure adequate elimination. 
Sodium Thiosulphate and Liver Extract. — McNally213 thought a patient of 
his showed some improvement while gr. 15 (1 gm.) of sodium thiosulphate in 
10 c.c. water was being given intravenously every other day. He cites the feeding 
by Charles of liver to these patients with what appeared to be improvement in 
some. When improvement under liver was noted, it was rapid and occurred in 
the first few days of the therapy. The use of liver extract intramuscularly, then, 
in dosages of from 15 to 30 units a day for four consecutive days and the repeti- 
tion of this dose two or three times a week over an indefinite period of time, 
depending upon the individual patient, has been suggested. 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: TREATMENT 
Chromium 
Scrubbing Tissue. — If the lesion or lesions, “ chrome holes ” or ulcers, are 
small and superficial, the damaged tissue may be scrubbed thoroughly with 5 
per cent, sodium hyposulphite, water or normal saline solution. The purpose of 
this treatment is to dislodge all tissue containing chromium compounds so that 
additional damage by burrowing will not occur. After this scrubbing, the wound 
may be treated like any abrasion of similar severity. 
Wet Dressings. — If the ulcers already are too deep for such scrubbing, wet 
dressings of sodium hyposulphite for a period of from three to five days should 
be applied to aid in the reduction of the chromium compound. Since the chro- 
mium in the flesh is not dislodged by sodium hyposulphite, wet dressings of 
from 5 to 10 per cent, solution of sodium citrate, sodium lactate or potassium 
and sodium tartrate should be applied to accomplish this. These wet dressings 
are continued for from three to five days. At times necrotic tissue in the ulcer 
will require curettage. Suppuration rarely occurs in chrome ulcers, but cleansing 
with a mild antiseptic agent following use of reducing agents may be used. Treat- 
ment appropriate for any ulcer is used following the therapy outlined above. 
Frequently it is desirable to remove the worker from his customary duties, at 
least during the early stages of treatment. 
Prophylaxis. — Prophylactic measures should consist of removal of fumes and 
dust from the atmosphere, cleanliness within the plant and confining the process 
within enclosures wherever possible. Respirators or gas masks should be worn. 
Shower baths and change of clothing should follow the day’s work, and the instal- 
lation of shower baths and locker rooms will encourage this procedure. The skin 
should be protected by suitable clothing, rubber gloves, protective ointments or 
oils. The nasal mucosa should be sprayed with an oil prior to going to work. 
Metal Fume Fever 
La Grippe Regimen.—No specific therapy is indicated in these cases. Pa- 
tients may be treated as though they had la grippe. The administration of 
acetylsalicylic acid, gr. io (0.6 gm.), every four to six hours combined at times 
with codeine phosphate, gr. \ to 1 (30 to 60 mgm.), will afford relief. The forcing 
of fluids, water and fruit juices, the use of hot drinks and rest in bed are of value. 
These patients will become symptom-free after absence from exposure for a short 
time, but for their composure the above regimen is prescribed. 
Prophylaxis. — The most valuable point, however, is to adopt an adequate 
medical and engineering program for prevention of the metal fume fever. The 
toxic fumes should be controlled at their source by having operations, which give 
Vol. IV. 944 ARSENIC 
rise to metal fumes, carried on, if possible, in a closed process. Usually it will be 
more practical to employ exhaust ventilation with hoods over the process pro- 
ducing the fume. The ventilating system should be designed so that a current 
of clean air is drawn past the operator and away from him toward the work. 
Masks and respirators may be provided for protection under unusual circum- 
stances. 
Magnesium 
When compared with other metals, the toxicity of magnesium is low, yet 
several disturbances to the body may occur from exposure to it. When alloyed 
with other metals, a rather typical metal fume fever may occur; secondly, peculiar 
cutaneous lesions may result from implantation under the skin of small particles 
of magnesium, and finally, severe burns of the body may occur due to the explo- 
sibility and inflammability of the dust of magnesium. 
The prevention and treatment of the systemic reaction is the same as that 
indicated under metal fume fever. McCord210 and his workers found that mag- 
nesium in the tissues reacts with the tissue fluids to give rise to the formation of 
hydrogen. The gas tends to remain localized in discrete nodules and is followed 
by a necrosis of the tissue simulating fibroblastic proliferation. This accounts 
for the slow healing of even minor wounds from small particles of magnesium. 
The treatment of these wounds demands anesthetization of the involved area 
and then a careful debridement of the tissue to insure complete removal of all 
particles. Burns from molten magnesium likewise should be debrided and all tis- 
sue apt to contain the metal removed. The denuded area should then be dressed 
with 5 per cent, sulfanilamide ointment. 
Arsenic 
General Measures. — As with mercury, phenol and other intoxicants the cases 
of acute poisoning from arsenic will be rare in industry. When they do occur, 
the symptoms of vomiting, painful diarrhea, nervousness, thirst, cyanosis and cir- 
culatory collapse must be treated. Early, abundant, gastric lavage with warm 
water is indicated. This is followed by the administration of warm milk. Pre- 
viously lavage of the stomach with colloidal ferric hydroxide suspension, pre- 
pared by adding magnesium oxide to tincture of ferric chloride or a solution of 
ferric sulphate, was advised. This is now considered by most to be almost obso- 
lete, but as McNally-13 points out, it can do no harm and may delay absorption 
while the stomach is being washed out repeatedly. 
Relief of Pain and, Diarrhea. — Morphine sulphate, gr. \ (15 mgm.), every 
four to six hours, may be needed for relief of the pain and may aid in controlling 
the diarrhea. Other drugs, which may be used for relief of the diarrhea and 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PREVENTION 
abdominal pain, include bismuth subcarbonate or subnitrate, gr. 15 (1 gm.), 
every four to six hours, tincture of opium, 10 to 15 drops, every four to six hours, 
or camphorated tincture of opium, paregoric, two drachms (8 c.c.), every three 
to four hours. Approximately two hours prior to starting these latter drugs, it is 
advisable to give a saline cathartic in full dose. 
For the diarrhea the drugs mentioned above, e.g., tincture of opium, bismuth 
subcarbonate or subnitrate or paregoric, may be used. Porter261 has reported 
prompt improvement of the diarrhea and neuritis by the use of 2.6 mgm. of thia- 
mine hydrochloride daily, but if this vitamin is used, larger dosages, from 50 to 
60 mgm. per day parenterally, are indicated. The use of nicotinic acid, from 
100 to 200 mgm. daily, possibly would be of value in treatment of the diarrhea. 
Cyanosis, Circulatory Collapse and Shock. — For cyanosis oxygen inhala- 
tions are given, and circulatory collapse and shock are treated as described in other 
sections, e.g., Mercury and Fluorine. The intravenous infusion of 5 to 10 per 
cent, dextrose in 1,000 c.c. physiological saline is indicated not only for treatment 
of the shock syndrome but also for the dehydration and chloride loss which may 
follow prolonged vomiting and diarrhea. The amount of this intravenous therapy 
needed will be determined by the patient’s course. 
Sodium Thiosulphate. — The use of sodium thiosulphate intravenously in 
both the acute and chronic cases is advised. There has been considerable con- 
troversy concerning the use of this drug, but clinically it appears to be of value. 
Ayres and Anderson8 demonstrated an increase in the excretion of arsenic in the 
urine following the injection of sodium thiosulphate in 80 per cent, of 49 cases. 
The amount to be used may vary from gr. 15 (1 gm.) in 10 c.c. of sterile dis- 
tilled water every four to six hours during the first twenty-four hours of the acute 
stage to a similar injection two or three times a week over a period of weeks in 
the chronic case. 
Skin Reactions. — The ulcerations, pigmentation and varied forms of a scal- 
ing dermatitis which may be present in the chronically exposed usually disappear 
after removal from exposure. The following prescriptions may be of value for 
the dermatitis: 
Salicylic acid 
Sulphur (ppt.) 
Lanolin 
22% grains (1.5 gm.) 
22! grains (1.5 gm.) 
i| drachms (6.0 gm.) 
Ung. aqua rosae 
1 ounce q.s. ad (30.0 gm.) 
Salicylic acid 
Menthol 
Lard 
\\ drachms (6.0 gm.) 
20 minims (1.2 c.c.) 
2 ounces q.s. ad (60.0 gm.) 
Fluids should be forced, and some of the drinking water should be normal 
saline solution. Milk and a high caloric, high vitamin diet are of general value. 
Vol. IV. 944 CADMIUM 
Peripheral Neuritis. — Vilter, Aring and Spies320 report striking improve- 
ment in a case of arsenic peripheral neuritis, in which 20 mgm. of synthetic vita- 
min B6 in sterile physiological solution of sodium chloride was given twice daily. 
Improvement was more marked when 50 mgm. of alphatocopherol was given 
intramuscularly in conjunction with the vitamin B6; 50 mgm. of thiamine hydro- 
chloride intravenously for three weeks had failed previously to influence the con- 
dition. Physiotherapy also may improve the neuritis. Anemia, if present, should 
be treated by ferrous sulphate, gr. 5 (0.3 gm.), two tablets three times daily. 
Arsine Poisoning. — No specific treatment is available for arsine poisoning. 
Repeated transfusions are of value, and the administration of iron compounds 
orally is indicated. Oxygen inhalations will be needed in many cases. The 
remainder of the treatment should consist of an adequate fluid intake supple- 
mented by frequent intravenous infusions of 5 to 10 per cent, dextrose in physio- 
logical saline. The administration in the early morning of saturated solutions 
of magnesium sulphate, \ to 2 ounces (15 to 60 c.c.), flavored with a small amount 
of compound tincture of cardamon, may help in encouraging the flow of thick bile 
plugging the biliary passages; this, however, is doubtful. A similar attempt 
might be made by introducing from 40 to 50 c.c. of 33 per cent, magnesium sul- 
phate through a duodenal tube. The stimulants frequently mentioned in other 
sections, e.g., the section describing Mercury, are to be used, when symptoms of 
circulatory or respiratory failure appear. 
Cadmium 
Drugs for Respiratory Relief. — The less seriously affected usually experi- 
ence sensations similar to an upper respiratory infection, and measures commonly 
used for the latter often afford relief. These include the use of acetylsalicylic acid, 
gr. 10 (0.6 gm.), every four to six hours, capsules containing acetylsalicylic acid, 
gr. 5 (0.3 gm.), phenacetin, gr. (0.15 gm.), and caffeine citrate, gr. (30 
mgm.), at three hour intervals or capsules of codeine sulphate, gr. \ (15 mgm.) 
and papaverine hydrochloride, gr. \ (15 mgm.), at from four to six hour periods. 
A combination of ephedrine sulphate, gr. £ (8 mgm.) and amytal, gr. f (24 mgm.), 
at from three to four hour intervals, may afford relief in some. Any of numerous 
cough syrups containing codeine phosphate or sulphate, pantopon or dilaudid 
hydrochloride in combination with expectorants such as ammonium chloride, may 
be of value, e.g.: 
Codeine sulphate 7i grains (0.5 gm.) 
Ammonium chloride 4 drachms (16.00 c.c.) 
Syrup of citric acid 1 ounce (30.00 c.c.) 
Water to make 4 ounces (120.00 c.c.) 
Sig.: Teaspoonful every three to four hours INDUSTRIAL TOXICOLOGY: TREATMENT 
Irrigations and Gargles. — Irrigation of the throat with warm salt and soda 
solution, a teaspoonful each of sodium chloride and sodium bicarbonate in one 
pint of water, or warm glucose solution, corn syrup one part and water two parts, 
every two hours, may be undertaken. If irrigations are not possible, then gargling 
either with the salt and soda solution, with 1:5,000 potassium permanganate or 
with five 5 gr. aspirin tablets crushed in a glass of water may be substituted. 
Neither the use of silver preparations nor the frequent vigorous swabbing of the 
throat with other preparations is recommended. 
Inhalations. — In some instances inhalations of the following might prove 
soothing: 
Menthol 
Camphor 
. • aa 4 drachms (15.0 gm.) 
Oil of eucalyptus 
Oil of dwarf pine needles 
aa i ounce (30.0 c.c.) 
Sig.: One teaspoonful in one pint of water, steamed and inhaled. 
Sedation in the form of barbiturates and intranasal drops may be needed, of from 
0.25 to 0.5 per cent, neosynephrin or 0.33 per cent, ephedrine in aqueous solution. 
Oxygen Therapy. — Whenever a patient appears to be moderately overcome 
by these fumes, placing him immediately within an oxygen tent is strongly recom- 
mended. This should be instituted without waiting for any signs of pneumonia 
for, as indicated in our fatal case, these may be absent. Furthermore, irrespective 
of the presence or absence of pneumonia, oxygen therapy affords a relief for the 
air hunger which exists. If a specific organism is suspected to be present as a 
secondary invader, appropriate chemotherapy should be introduced. 
Prophylaxis. — Those responsible for the health of workmen should recognize 
the danger of cadmium and adopt adequate means of removing all fumes by 
exhaust systems. Workmen should wear respirators at all times when in prox- 
imity to cadmium fumes. 
Zinc 
Prophylaxis. — The preventive measures are the same as those to be adopted 
with a lead hazard or any dust hazard apt to contain lead. Adequate ventilation, 
avoidance of the deposits of dust and frequent cleaning of all parts of machinery, 
floors and walls of collected dust are factors in reducing exposure. Men should 
be selected, who are free from focal infection. Some authors advise periodic 
changes of work and comparatively short working hours. The inclusion of ade- 
quate fat and milk in the diet is thought to prevent to some degree the occurrence 
of symptoms in those working with zinc. 
If a case of chronic zinc poisoning has been established, the patient should be 
Vol. IV. 944 SELENIUM AND TELLURIUM 
removed from his hazard at once. Anemia, if present, is treated by ferrous sul- 
phate, gr. 5 (0.3 gm.), two tablets three times a day. In acute intoxication a few 
days’ absence from the work and treatment as described under Metal Fume 
Fever will suffice. 
Zinc Chloride Burns. — Proper treatment of zinc chloride burns consists of 
the removal of the necrotic slough and of filling the wound with sodium bicar- 
bonate. Compresses of a warm solution of sodium bicarbonate are to be used 
then. After the lesion has cleaned up to some extent, it is to be dressed with borated 
petrolatum, painted with merthiolate or covered with metaphen in collodion. 
Gloves should be worn by workers handling flux containing zinc chloride. When 
zinc chloride powder is handled, ordinary washing with soap and water will not 
remove it, as a rule, while a 5 per cent, solution of hydrochloric acid will. 
Selenium and Tellurium 
Prophylaxis. — The air breathed by workers should be free of these substances 
or their presence reduced to a minimum. Frequent sampling is necessary to 
accomplish this. If the substances are subjected to high temperatures, exhaust 
ventilation should be in operation. The skin should be protected to prevent in- 
volvement. Workmen with known respiratory conditions, impaired liver func- 
tion or arthritic tendencies should be excluded from this hazard. 
In chemists synthesizing organoselenium compounds absorption through the 
skin is prevented by frequent changes to new gloves, protective cream and scru- 
pulous care in handling products. Protective devices such as rubber and synthetic 
rubber gloves give only temporary protection, since some compounds, e.g., methyl- 
benzoselenazole, readily penetrate them. 
Diuretics and Cathartics. — No specific treatment for poisoning with selenium 
and tellurium is outlined, but if intoxication has occurred, removal from the ex- 
posure with possible hospitalization is necessary. The use of diuretics to secure 
adequate elimination may be indicated, e.g., ammonium chloride, gr. 15 (1 gm.), 
from four to six times daily, or theophylline, gr. 3 (0.2 gm.), three times daily. In 
this regard saline cathartics are useful, such as magnesium sulphate, \ to 1 ounce 
(15 to 30 gm.), the effervescent preparation of magnesium citrate, 12 ounces, 
sodium phosphate, 1 drachm (4 gm.), or the effervescent preparation of sodium 
phosphate, 2\ drachms (10 gm.). 
Relief of Symptoms. — Upper respiratory symptoms may be treated as de- 
scribed under Cadmium. Intravenous 50 per cent, dextrose, 50 to 100 c.c., may 
aid in edema of the lungs, as may salyrgan, \ to 2 c.c., intravenously at intervals 
of three or four days. If kidney degeneration is present, the use of salyrgan 
probably is contraindicated, although some believe that salyrgan may be used 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PREVENTION 
even in the presence of definite kidney pathology. Inhalations of oxygen by 
intranasal tube or by a tent may be needed, and intravenous infusions of 10 pei 
cent, dextrose in physiological saline (1,000 to 3,000 c.c. daily) may be neces- 
sary, if vomiting or diarrhea is present. 
Diet. — The use of a high carbohydrate diet with an increased water intake 
has been suggested as has the use of concentrates of the vitamin B complex. Ex- 
perimental work on animals indicated the protective action against selenium of a 
diet high in protein and low in carbohydrate. There was also some evidence that 
the ratio of selenium to the protein in the diet seems to determine the toxicity of 
selenium in food, and that the quality of protein, as well as the quantity, was of 
importance. For example, casein and lactalbumin tend to counteract the toxicity 
of selenium, while edestin and gelatin are not effective. 
The trial of similar diets in selenium poisoning in human beings has not been 
reported, but the use of diets high in proteins, such as casein, lactalbumin, etc., 
might well be worth while in treatment of these patients. In addition, when liver 
damage is present, the use of a high carbohydrate, high protein diet should be 
followed. 
Also experimentally sodium arsenite, five parts arsenic per million of drink- 
ing water, completely prevented symptoms of selenium poisoning. Clinical use 
of this in treatment of selenium poisoning has not been reported. 
Vanadium 
Symptomatic. — Since but few cases have been reported, and there is no gen- 
eral agreement about the symptoms, treatment should be directed to the indi- 
vidual case of proved exposure. If Symanski306 is correct, symptomatic treatment 
would be directed at the conjunctivitis, the nasopharyngitis and the bronchitis. 
Some of the detailed therapy directed at the upper respiratory symptoms, as de- 
scribed under Cadmium, may be followed. 
Prophylaxis. — In mixing rooms respirators or masks should be worn, and 
suction apparatus should be installed. Rotation of workers should be practiced, 
so that they would have days or weeks in which they could recuperate from effects 
of contact with vanadium. 
Cyanides 
Methylene Blue Treatment. — Hanzlik and Richardson126 outlined the most 
effective measures for treatment in cases of acute cyanide poisoning. Fifty c.c. 
of i per cent, methylene blue solution containing i .8 per cent, sodium sulphate is 
injected intravenously and is repeated, if necessary, until 200 c.c. are injected. 
Vol. IV. 944 CYANIDES 
Frequently consciousness and reflexes are restored before the first 50 c.c. have 
been completely injected, but if the patient lapses into unconsciousness or mani- 
fests respiratory depression, the methylene blue treatment should be resumed. 
As quickly as possible proceed with gastric lavage using 5 per cent, sodium thio- 
sulphate; this oxidizes any unabsorbed poison. For lavage 3 per cent, hydrogen 
peroxide or 0.2 per cent, potassium permanganate solution may be used, if sodium 
thiosulphate is not at hand. Artificial respiration or 5 to 7 per cent, carbon 
dioxide with oxygen may be needed. 
Circulatory and Respiratory Stimulants. — Caffeine sodium benzoate, gr. 
(0.5 gm.), coramine, 1.5 c.c. or metrazol, gr. \\ to (0.1 to 0.3 gm.), intra- 
muscularly, may be needed for circulatory and respiratory stimulation. 
Sodium Nitrite Treatment. — An alternative treatment is as follows. Give 
at once a slow and careful intravenous injection of 1 per cent, sodium nitrite 
solution in five divided injections until 50 c.c. have been injected in about one 
hour. If improvement is manifested, but prognosis still is unfavorable, the injec- 
tion may be continued cautiously, but it is to be stopped at once in case of sudden 
collapse. Epinephrine, 1 c.c. of 1:1,000 solution, should be ready at hand to 
combat nitrite shock, if necessary. Fortify the nitrite treatment at once with 
the intravenous injection of 20 c.c. of freshly prepared 5 per cent, aqueous solution 
of sodium thiosulphate, filtered and, if necessary, continue the injection up to a 
total of 500 c.c. Treatment directed at further circulatory and respiratory stimu- 
lation is to be used as already indicated. The solutions used in these treatments 
can be sterilized readily by boiling for fifteen minutes. The methylene blue 
should not be dissolved in physiological solution of sodium chloride, since pre- 
cipitation occurs. 
Both the methylene blue and the sodium nitrite appear to act by producing 
methemoglobin, which in turn combines with the cyanides to decrease the poison- 
ous effects of the latter. Actually, sodium nitrite forms more methemoglobin, 
but this probably does not contribute to the physiological recovery from poisoning, 
and there is danger of sustained circulatory collapse to add to the already pre- 
carious state of the patient. 
Sodium Nitrite and Sodium Thiosulphate Treatment. — Ingegno and 
Franco149 treated two patients with 0.3 gm. sodium nitrite in 10 c.c. water given 
intravenously at the rate of 2.5 to 5 c.c. per minute and followed this by 25 to 50 
c.c. of a 50 per cent, solution of sodium thiosulphate given through the same 
needle and at the same rate. They warned that the sodium nitrite and thiosul- 
phate must not be mixed before administration. If signs reappeared or persisted, 
one-half the dose of each antidote was repeated one hour later. They used also 
amyl nitrite inhalations for from fifteen to thirty seconds every two or three 
minutes. 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: TREATMENT 
Diet. — A high fat diet has been shown experimentally to reduce the mor- 
tality from sodium cyanide poisoning. In the rare case of chronic cyanide poison- 
ing such a diet possibly would be of use in addition to symptomatic treatment. 
The use of sodium thiosulphate, 10 c.c. of a 10 per cent, solution intravenously, 
two or three times per week might be of value. Removal at once from exposure 
is, of course, necessary. 
Carbon Tetrachloride 
The severe case of carbon tetrachloride poisoning will require a rigid regime, 
the purpose of which is twofold, to treat the liver and renal damage and to restore 
a normal blood chemistry. The patient should be removed from all contact with 
the substance. He should be supplied with an abundance of fresh air and with 
inhalations of from 5 to 7 per cent, carbon dioxide in oxygen, if necessary, for 
respiratory stimulation. 
Increasing Blood Calcium Level. — These patients have a low blood calcium 
level. Therefore, a high calcium intake should be provided to bring their blood 
calcium to a high or normal level, which it has been shown experimentally will 
prevent liver and renal damage to some degree. This can be accomplished by 
giving 10 c.c. of a 10 per cent, solution of calcium gluconate intravenously two 
or three times daily with 12 gm. calcium gluconate or 8 gm. of calcium lactose 
by mouth. 
Proteins in Diet. — The diet itself should contain a high proportion of carbo- 
hydrates, 200 to 250 gm. or more per day, together with a low fat and a low 
meat protein ratio. The meat protein is limited because of the evidence that 
increased retention of guanidine prolongs and increases the symptoms of carbon 
tetrachloride poisoning. However, in view of the demonstrated value of protein 
in liver regeneration, a high level of other forms of protein should be maintained. 
Actually, following the early acute symptoms a still higher protein level probably 
would be of value. Bread, milk, sugar and karo syrup are obviously of much 
value in the diet, to which may be added also extra vitamins. 
Dextrose Solutions. — The intravenous administration of from 2,000 to 3,000 
c.c. daily of 10 per cent, dextrose in physiological saline is indicated. In renal 
disease or when circulatory collapse induces defective renal function, the injec- 
tion of physiological solution of sodium chloride occasionally may produce or 
aggravate acidosis. This effect is brought about chiefly by diluting the bicar- 
bonate already in the body at a time when the kidneys are not excreting the 
excess of chloride. In some instances, then, the use of 10 per cent, dextrose in 
distilled water rather than in 0.9 per cent, sodium chloride solution may be indi- 
cated. However, in most instances the 0.9 per cent, sodium chloride solution 
Vol. IV. 944 CARBON TETRACHLORIDE 
may be used, since even abnormal kidneys excrete salt solution well, if serum 
proteins are not reduced, or if cardiac failure is not present. Dextrose solutions 
by providing food and aiding the circulation help the kidneys to adjust extra- 
cellular volume and concentration, when sufficient sodium chloride is available. 
The administration of from 50 to 200 c.c. of 50 per cent, dextrose intra- 
venously per day is of value also, but when cardiac involvement is present, not 
more than 50 c.c. should be given at one time. It has been suggested that some 
of the fluids may be given per rectum rather than intravenously; 120 c.c. of 10 
per cent, dextrose every four hours may be used rectally. 
Insulin. -—From 5 to 10 units of insulin three times per day may aid in the 
oxidation of the intermediate products of protein, fat and carbohydrate. There 
have been a few reports of the satisfactory use of Hartmann’s buffer solution and 
of methylene blue, but neither of these agents has been used extensively in 
these cases. 
Digitalis. — This has been advised routinely for the treatment of myocardial 
involvement but would seem to be of questionable value in most cases. When 
used, regular digitalizing doses of gr. i\ (0.1 gm.) should be employed. Epi- 
nephrine should not be used, particularly if myocardial involvement is present. 
Diuretics. — Diuretics other than the mercurial ones are indicated. In treat- 
ing oliguria or anuria the use of papaverine hydrochloride or sulphate, gr. \ (30 
mgm.) intravenously or by mouth, is said to be of value on the basis that these 
drugs relax the arteriolar spasm associated with the toxic nephritis. There are 
claims of success for the use of hexyl resorcinol for treatment of kidney irritations. 
Other Medication. — Free catharsis is of value, but oily preparations are con- 
traindicated. Transfusions of blood sometimes are necessary. If anemia of the 
secondary type is present, ferrous sulphate in enteric coated tablets, gr. 5 (0.3 
gm.), two tablets three times per day, should be prescribed, and if a macrocytic 
type of anemia accompanies the liver damage, the use of liver extract is indi- 
cated. If any bronchial conditions develop, inhalations of compound tincture 
of benzoin and pine-needle oil followed by a cough syrup containing codeine 
phosphate or sulphate should be used. Sedation may be necessary for the restless 
or for the excited. When the eyes are involved, their treatment should be con- 
signed to the ophthalmologist. 
Experimental work with a purified concentrated hog’s liver extract has dem- 
onstrated an accelerated healing of liver tissue in rats after carbon tetrachloride 
poisoning in addition to protection of the liver from damage. The active ingredi- 
ent appeared to be sodium xanthine. Its clinical use in carbon tetrachloride 
poisoning has not been reported so far. 
Prophylaxis. — From the standpoint of prophylaxis proper ventilation is 
essential. In addition closed systems should be used, or if these are not possible, 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PREVENTION 
positive pressure helmets may be necessary, when the concentrations are very 
high. Exhaust systems should be provided with intakes at the floor level rather 
than near the ceiling. The possibility of skin contact with the substance should 
be eliminated. There should be frequent examination of workers and careful 
selection of those who are to work with this hazard. Rotation of workers should 
be frequent. The diet of carbon tetrachloride workers should be high in calcium 
including at least one quart of milk daily. Alcoholic beverages should be avoided. 
Trichlorethylene 
Prophylaxis. — From the standpoint of prophylaxis several points are impor- 
tant. Addiction to this solvent has been reported by numerous investigators, and 
it is known that men at times will inhale it voluntarily. For this reason rotation 
of men should be practiced where this substance is used for long periods. In 
degreasing plants, where heat is used, acid-proof flues are necessary to carry off 
the fumes to the outside. If such flues are not provided, the gas heating process 
should be condemned. In the general use of trichlorethylene proper ventila- 
tion should be enforced strictly at all times, and the skin should be protected 
by clothing and gloves as nearly as possible. It is well to apply ointments of oil 
or fat, for example a mixture of equal parts of vaseline and rose water ointment, 
to areas such as the hands and arms, which are liable to be most exposed. 
Dermatitis. — For patients, who present a dry, fissured type of dermatitis, the 
chief therapy is similar to that suggested in those measures to be used in pro- 
phylaxis. The patient should be removed from exposure to the offending solvent 
until the dermatitis has cleared, and in quite a few cases it will be best to advise 
him to change his occupation, although careful protection of exposed parts of 
the body may prevent recurrence of the dermatitis. For the treatment of the 
acute dermatitis simple ointments, such as rose water with 1 per cent, phenol 
and 0.5 per cent, menthol, may be of value. 
The Acutely III Patient. Respiratory Stimulants. — These are needed. Here 
the most valuable of all will be inhalations of a mixture of from 5 to 7 per cent, 
carbon dioxide with oxygen. When such inhalations are not available, artificial 
respiration by the Schaefer method must be used, and later, if pulmonary edema 
is present, the administration of oxygen either by a tent or intranasal apparatus 
will be of value. It should be remembered, however, that oxygen in itself is not 
a respiratory stimulant, and when used without the addition of carbon dioxide, 
actually may depress rather than stimulate respiration. The intravenous or intra- 
muscular injection of coramine, 1.5 c.c. or the intramuscular injection of metrazol, 
pt. D to (0.1 to 0.3 gm.), are of questionable value in treatment of the respira- 
tory failure, although their use has been advised. 
Vol. IV. 944 TETRACHLORETHANE 
Shock. — They may, however, be of definite value if shock is present. For 
treatment of this from 1 to 2 c.c. of camphor in sterile oil or of caffeine sodium 
benzoate, gr. (0.5 gm.), may be used. Of much greater value will be the use 
of transfusions of citrated blood and the intravenous infusion of 1,000 c.c. of 10 
per cent, dextrose in normal saline solution. 
Diet. — Following the very acute period soft diet and normal fluid intake 
may be resumed, but if symptoms of nausea and vomiting persist, the use of from 
2,000 to 3,000 c.c. daily of 10 per cent, dextrose in physiological saline is advisable. 
The administration of thiamine chloride, vitamin B,, in dosages of from 30 to 60 
mgm. daily, at first parenterally, has been suggested in treatment of the neuro- 
logical manifestations. During the convalescence a high caloric diet with vitamin 
adjuncts should be given. 
Exposure to Phosgene. — If the acutely ill patient has been exposed to phos- 
gene resulting from the decomposition of trichlorethylene by gas flames, he may 
present a somewhat different picture, with pulmonary edema, dyspnea and cyano- 
sis playing prominent parts in the picture. Here again respiratory and circulatory 
stimulants are indicated. In addition venesection of 500 c.c. may be of value in 
treating the pulmonary edema. During World War I intratracheal medication 
of from 1 to 3 drachms of the following mixture two or three times per day 
was found to be beneficial after the very acute stages had passed; 5 per cent, 
each of guaiacol, camphor and menthol in liquid petrolatum or olive oil. No in- 
stances of lipoid pneumonia from the use of this preparation are mentioned. 
The Gray Stage. — During the acute phase a syndrome may occur, referred 
to in the findings of the chemical warfare service as the gray stage, in which pro- 
nounced pulmonary edema, almost utter inability to breathe and shock are seen. 
In such a stage the temperature falls, and there is a marked increase in blood 
concentration necessitating oral and intravenous administration of physiological 
saline solution. A fine degree of medical judgment is needed to balance the need 
for venesection on the one hand and for decrease in excessive blood concentration 
by administration of fluids on the other. 
Tetrachlorethane 
The chief concern in formulating a therapeutic regimen is directed toward the 
improvement of liver function. 
Diet. — The patient should be given a diet high in carbohydrate, since this 
food factor aids in the regenerative process of the iniured parenchymatous liver 
cells. In addition the inclusion in the diet of foods high in protein is indicated, 
since recent research indicates a protective action to the liver by diets high in 
protein. The ability of the liver to deaminize and metabolize amino acids appears 
Vol. IV. 044 INDUSTRIAL TOXICOLOGY: TREATMENT 
to be normal up to the very last stages of hepatic insufficiency. The fat content 
of the diet should be low; from 200 to 250 gm. of carbohydrate and from 1.5 to 
2 gm. of protein per kilogram of body weight thus should be included in the diet. 
Infusions of Dextrose. — It is of particular importance, when severe or even 
moderate liver damage is present, to administer by intravenous infusion from 5 
to 10 per cent, dextrose in physiological saline solution or in distilled water, 
preferably about 3,000 c.c. daily. It may be necessary in very acute cases to give 
such infusions by continuous intravenous drip. 
Vitamin K and Bile Salts. — The use of 2-methyl-i, 4-naphtho-quinone, syn- 
thetic vitamin K, and of bile salts has been suggested. Vitamin K may be given 
orally or parenterally in doses of from 1 to 4 mgm. daily, and the bile salts may 
be administered orally in dosages of from 2 to 3 mgm. of desiccated whole fresh 
bile. Prior to the administration of these substances the prothrombin level of 
the blood should be determined, and a subsequent check on this reading will indi- 
cate whether the vitamin K is of value in the individual case. 
On the question of the value of vitamin K in such cases there is considerable 
disagreement. There is evidence to indicate that, if hepatic injury is severe 
enough, vitamin K is not effective in correcting the prothrombin deficiency. 
Since, however, little toxic reaction to vitamin K or to whole fresh bile occurs, 
their trial use is suggested. In cases of hemorrhage blood transfusion is indicated, 
and for secondary anemia, if present, enteric coated tablets of ferrous sulphate, 
gr. 5 (0.3 gm.), two tablets three times daily, should be used. The intravenous 
administration of 10 c.c. of a 10 per cent, solution of calcium gluconate twice 
daily will be of value. The oral use of 12 gm. calcium gluconate or 8 gm. calcium 
lactate will supply about 1 gm. of calcium daily. Under normal conditions the 
daily calcium requirement is from 0.5 to 1 gm. 
Methyl Chloride 
Inhalations and Artificial Respiration. — Severely exposed workmen should 
be removed at once from contact with the substance. Inhalations of from 5 to 7 
per cent, carbon dioxide in oxygen certainly are indicated, and artificial respira- 
tion may be needed. In this phase of the treatment the object is to remove from 
the lungs all possible methyl chloride. It is felt by some that these inhalations 
should be continued every three hours over the first twenty-four to forty-eight 
hours. The respiratory and cardiac stimulants frequently mentioned in other sec- 
tions, e.g., the section on Phenol, should be used when respiratory or circulatory 
failure appears. 
Treatment as in Methyl Alcohol Poisoning. — The methyl chloride taken into 
the body is decomposed into methyl alcohol and hydrochloric acid. The latter 
Vol. IV. 944 CHLORINATED NAPHTHALENES AND DIPHENYLS 
forms relatively innocuous substances such as potassium and sodium chlorides in 
the blood. The treatment for the methyl chloride poisoning, then, becomes the 
same as for methyl alcohol poisoning. The patient is hospitalized immediately, 
and energetic treatment of his acidosis is begun. For details of this section on 
Methyl Alcohol should be consulted. 
Convulsions and Restlessness. — If convulsions occur, they require 1 drachm 
(4 gm.) of potassium bromide in 4 ounces (120 c.c.) of water as a retention enema, 
but under no conditions should chloral or chloroform be given. For the convul- 
sions and restlessness the use of other sedatives such as phenobarbital, seconal, 
nembutal, sodium amytal and sodium luminal as well as others of this type may 
be of value. 
Abdominal Pain. — Some cases, in which paroxysms of severe abdominal pain 
have been a prominent part of the picture, are reported. In these morphine 
sulphate, gr. (15 mgm.), has been used together with intravenous calcium. 
It would appear of value in cases presenting such severe cramps to use 10 c.c. of 
10 per cent, calcium gluconate intravenously, repeated as needed. The use of 
1 c.c. of 1:2,000 prostigmine methylsulphate with the morphine may enhance its 
effectiveness and allow reduction of the amount of morphine. 
Anemia. — If this develops, it is to be treated with ferrous sulphate, gr. 5 (0.3 
gm.), two or three times a day, if it is of a secondary type; if it appears to be of 
a macrocytic type, it is to be treated with liver-extract preparations. 
Ethylene Dichloride 
Treatment should consist of general supportive measures as indicated with 
the other solvents and of similar prophylaxis. The use of a high carbohydrate, 
high calcium diet has been of definite value. The intravenous administration of 
io c.c. of io per cent, calcium gluconate to the patient shortly after his admission 
to the hospital has relieved markedly the epigastric cramps and vomiting. This 
presumably is because of the relaxing effect on smooth muscle of the calcium 
gluconate. As in treatment for the other solvents it will be valuable to use intra- 
venous infusions of from 5 to 10 per cent, dextrose in physiological solution of 
saline, if chloride loss following vomiting is present, or in distilled water, if it 
is felt that the salt content will increase renal damage, in amounts varying from 
2,000 to 3,000 c.c. 
Chlorinated Naphthalenes and Diphenyls 
Prophylaxis. — It should be reiterated constantly that the primary treatment 
is prevention. Ventilation should be proper. The recommendations of Green- 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PREVENTION 
burg09 and his associates concerning the type of person to be employed, where this 
hazard exists, should be followed. The knowledge of an existing hazard by both 
the employer and the employee and the recognition of certain early symptoms by 
the workman will greatly reduce actual intoxication. Obviously this is an edu- 
cational program. 
No specific therapy has been evolved for these cases. The acneform skin 
lesions and the liver damage are the two symptoms toward which treatment is 
to be directed chiefly. 
Skin Lesions. — Prevention of the papulopustular skin eruption frequently 
may be accomplished by installation of showers and by the formulating of rules 
requiring a change from street clothing to work clothing at beginning of the day’s 
work and, following a shower, a change back to street clothing at the end of the 
work period. The most satisfactory treatment of the skin eruption, once it has 
occurred, consists of quartz light and x-ray therapy together with mechanical 
removal of the comedones. The worst cases are to be treated with quartz light 
each day for from 15 to 20 minutes, the less serious ones three times per week, 
and the mild ones once per week. The pustules should be opened, and these 
might respond well to the use of sulfathiazole powder or ointment locally. Ex- 
treme body cleanliness should be practiced. Cases of very resistant exfoliative 
dermatitis have been described, in which the use of sodium thiosulphate, splenic 
extract, calcium gluconate, autohemotherapy, roentgen therapy and numerous 
baths, powder and ointments were of little avail. 
Liver Disorder. — This may be treated much as described under Tetrachlor- 
ethane, the chief points being a high carbohydrate, high protein diet with ade- 
quate fluid intake and particularly, intravenous infusions of 5 to 10 per cent, 
glucose in normal saline solution in amounts of from 2,000 to 3,000 c.c. or more 
daily. The use of calcium and of sodium xanthine experimentally has been of no 
value in prevention or treatment of the liver damage due to the chloronaphtha- 
lenes. This differs, for example, from the treatment of carbon tetrachloride 
poisoning in which calcium products are of much value. 
Alcohols: Glycols: Alcohol-Ethers 
All alcohols have a narcotic effect, which is progressively greater with increase 
in molecular weight. The higher alcohols, like butyl and amyl alcohol, have in 
addition an irritant action as well as some poisonous action on the protoplasm. 
Whenever any of these are used industrially, adequate ventilation is essential for 
protection of the workers. 
Special Measures in Industrial Cases. — The treatment of the case of methyl 
alcohol poisoning seen in industry will differ to some extent from that seen in 
Vol. IV. 944 ALCOHOLS: GLYCOLS: ALCOHOL-ETHERS 
private practice. In industry the toxic action usually will have been produced 
by absorption through the skin or by inhalation in contradistinction to the inges- 
tion of the product more commonly seen in private practice. For this reason the 
use of emetics is not indicated, and the value of gastric lavage with 4 per cent, 
solutions of sodium bicarbonate will not be so great, although this latter pro- 
cedure may be used and will, at least, be of value in treating the resulting acidosis. 
Correction of Acidosis. — The most important phase of the treatment is di- 
rected at correcting the acidosis, which is produced in the body by the formation 
of formic acid from the methyl alcohol. It has been the writer’s experience to find 
that medical literature frequently advises treatment of acidosis but fails to give 
details of such treatment. For this reason some detail in the treatment of acidosis 
is included here. In other sections, where treatment of acidosis is suggested, 
reference to this description has been made. The use of sodium bicarbonate or 
sodium lactate intravenously is advisable. It is safest to calculate the dose neces- 
sary to restore the serum bicarbonate according to the method of Hartmann 
and Senn128: 
(6o-CO.,)o.7W 
mM. == 
2.24 
mM. = millimols of sodium bicarbonate or sodium lactate 
CO. = serum carbon dioxide content in volumes per ioo c.c. 
W = body weight in kilograms 
One mM. of sodium bicarbonate is 0.084 gm.; 1 mM. of sodium lactate is con- 
tained in 1 c.c. of 5-molar sodium lactate. In marked acidosis, when serum carbon 
dioxide is not known, 5 mM. of sodium bicarbonate (1.4 gm.) per kilogram of body 
weight is a safe dose. Hartmann and Senn128 recommend the injection of one-half 
the calculated dose of sodium lactate intravenously and one-half subcutaneously 
as one-sixth molar sodium lactate. R-molar sodium lactate is obtainable in ster- 
ilized ampules, which most physicians will find more convenient than sodium bicar- 
bonate. Sodium bicarbonate cannot be boiled or autoclaved in an unsealed vessel 
without forming the highly toxic sodium carbonate. Sodium bicarbonate may be 
weighed and added with aseptic precautions to sterile water or dextrose solution 
and injected intravenously as a 2 to 5 per cent, solution. Both sodium bicarbonate 
and sodium lactate may be given by mouth, when the patient is able to take them 
by this route. 
Solutions for Use in Acidosis. — Several very valuable solutions for use in treat- 
ment of acidosis are on the market. A solution containing sodium chloride, 6.5 
gm., sodium bicarbonate, 2.5 gm. and potassium chloride, 0.18 gm. per liter, may 
be prepared by the addition of the contents of a 50 c.c. ampule of this preparation 
to 500 c.c. of sterile water. It may be used in practically all cases of acidosis with- 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: TREATMENT 
out additional sodium bicarbonate and may be given subcutaneously or intra- 
venously. Lactate-Ringer’s solution, sodium chloride, 6 gm., sodium lactate, 2.7 
gm., potassium chloride, 0.4 gm. and calcium chloride, 0.2 gm. per liter, is equally 
valuable and is available in concentrated form in ampules the contents of which 
are to be diluted with distilled water. 
Other Measures. — In addition to treatment of the acidosis the patient should 
be kept warm. Intravenous infusion of 10 per cent, dextrose in physiological 
saline may be of value in supporting him, and for this there has been advised also 
the intramuscular administration of atropine sulphate, gr. 1/40 mgm.), not 
to be repeated, strychnine sulphate, gr. 1/30 (2 mgm.), metrazol, gr. i\ (0.1 gm.), 
camphor in oil, 1 to 2 c.c., coramine, 1.5 c.c., or caffeine sodium benzoate, gr. 
(0.5 gm.). Aromatic spirits of ammonia, \ to 1 drachm (2 to 4 c.c.), by mouth 
is said to be of value. If pain is present, the use of morphine sulphate, gr. \ (15 
mgm.), despite its central depressant effect, or codeine phosphate, gr. 1 (60 mgm.), 
is used frequently, and if delirium is present, scopolamine hydrobromide, gr. 1/300 
to 1/200 (0.2 to 0.3 mgm.), may be combined with the morphine. 
Use of 50 per cent, solutions of sucrose in treatment of cerebral edema, if 
present, has been suggested. The oral administration of a large dose of magnesium 
sulphate usually is part of the routine. With the exception of the eye most abnor- 
malities from chronic exposure clear up after removal of the exposure. 
Benzene (Benzol) and Its Homologues 
What is said here of treatment for benzene may be applied to toluene, xylene 
and a few of the less toxic homologues of benzene. 
Prophylaxis. Frequent Physical and Laboratory Examinations. — Constant 
vigilance by blood examinations and air analysis should be the established order 
wherever benzene constitutes a hazard. The routine white cell count commonly 
resorted to should be supplanted by a complete blood study for reasons emphasized 
in earlier paragraphs of this chapter. Only those in fine physical condition should 
be placed where a benzene hazard may arise, and frequently physical as well as 
laboratory examinations are indicated. 
Men should be rotated, and when the least variation from the normal is noted, 
the worker should be removed from his exposure. Likewise workers should be 
instructed to report for examination upon noting bleeding from the nose or gums 
or other mucous membranes, or when unaccountable subcutaneous hemorrhages 
or discolorations are noted. Safety engineers have done an excellent job of pre- 
venting accidents by educating the employees regarding the dangers, which exist 
in certain types of employment. It is high time for a similar educational cam- 
paign to be conducted in the various occupational diseases. Many serious cases 
Vol. IV. 944 BENZENE (BENZOL) AND ITS HOMOLOGUES 
of poisoning from benzene and other noxious agents could be prevented, if the 
employees themselves knew, or were informed of, certain early signs or symptoms. 
To find a case of far advanced anemia in one, who for some time had noted bleed- 
ing and other symptoms of general malaise without reporting these, denotes not 
only ignorance on his or her part but a failure in education or instruction. 
Proper Ventilation. — Obviously proper ventilation is extremely important. 
Since benzene fumes tend to form pockets and are very diffusible and heavier than 
air, the ventilation should be general and from the floor by means of suction. 
Dermatitis. — Dermatitis is prevented by the rubbing into the skin of olive 
oil or other animal or vegetable fat or by the use of a wax ointment before handling 
the substance. Rubber gloves may be used, but ordinarily they do not withstand 
the action of benzene, so synthetic rubber, which resists the solvent action much 
better, should be substituted. 
Anemia. Blood Transfusions. — In those workers, who have developed ane- 
mias of varying degrees together with other symptoms of benzene poisoning, the 
most valuable form of therapy is blood transfusion repeated frequently, if neces- 
sary. In attempting to carry out this type of therapy, Gray, Greenfield and Led- 
erer97 were confronted with a case of autohemagglutination, although the patient 
had had three previous transfusions. They point out that autohemagglutination 
is the interaction of the agglutinin of the serum with the agglutinogen of the red 
blood cell and can occur only at a temperature below that of the body. They 
eliminated the difficulty by heating the serum and cells to body temperature. 
Liver Extract and Iron. — Since the anemia frequently is of the macrocytic, 
hvperchromic type, liver extract intramuscularly in large dosages, 15 to 30 units 
daily for four days, then every two or three days, or ventriculin orally, 15 to 30 
gm. daily, sometimes both, should be tried. If the anemia appears to be of a 
secondary type, the use of iron in the form of ferrous sulphate, gr. 5 (0.31 gm.), 
two or three times a day, is advised. Leucopenia indicates the trial of pentnucleo- 
tides intramuscularly, 10 to 40 c.c. daily, although marked improvement under this 
form of therapy usually has not been demonstrated in these cases. 
Roentgen Rays. — For further stimulation of the blood forming organs, the 
use of roentgen therapy to the long bones and spleen and bone marrow extracts 
has been suggested. Others have used ascorbic acid in moderately large doses with 
reported success. 
Diet. — The diet should contain nourishing food with an excess of animal fats 
and a high calcium content. Calcium preparations may be given orally as sup- 
plements to the diet. Intravenous infusions of from 1,000 to 3,000 c.c. daily of 
from 5 to 10 per cent, glucose in saline are of value. Good results from the use 
of ascorbic acid in daily doses of from 200 to 400 mgm. intravenously and orally, 
until a normal vitamin C level is attained, have been claimed. 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PREVENTION 
Mouth, Nose, Throat and Skin Hygiene. — Because these patients frequently 
die of a terminal infection, particular attention should be paid to mouth, nose, 
throat and skin hygiene. 
Phenol 
Principal Steps. — The case of phenol poisoning encountered in industry usu- 
ally will differ from that seen in private practice in that the mode of poisoning will 
be by absorption through the skin or by inhalation in the form of vapor rather 
than by drinking of the material. The most important steps, then, in the acute 
case of industrial phenol poisoning will be; (1) the removal of all clothing to pre- 
vent further absorption, (2) washing of all involved areas on the skin with a 25 
per cent, solution of either alcohol or glycerin and (3) treatment of shock. 
Respiratory and Circulatory Measures. — The patient should be kept as warm 
as possible, and symptoms of circulatory shock and respiratory depression should 
be treated by use of the various stimulants mentioned in previous sections. For 
respiratory stimulation the most valuable are inhalations of oxygen with from 5 to 
7 per cent, carbon dioxide and solutions such as metrazol, gr. i\ (0.1 gm.), cam- 
phor in oil, 1 to 2 c.c., caffeine sodium benzoate, gr. (0.5 gm.), intramuscularly 
or coramine, 1.5 c.c., intravenously or intramuscularly. For the circulatory shock 
intravenous infusion of 1,000 c.c. of 10 per cent, glucose in distilled water and 
drugs such as the coramine, caffeine or epinephrine hydrochloride, \ to 1 c.c. of 
1:1,000 solution intramuscularly, may be used. However, there is some question 
concerning the advisability of the use of epinephrine in cases of poisoning. The 
use of digitalis preparations is mentioned frequently in treatment of circulatory 
shock but seems of very questionable value in this situation. 
First-aid Measures. — As first-aid measures a quantity of olive oil, cod-liver 
oil, cottonseed oil, castor oil or any other available vegetable oil should be given 
by mouth as well as egg-white. Mineral oil affords no protection against phenol, 
since the solubility of phenol in it is quite small, about i in 50 parts. Alcohol, 
previously thought to be of value, should not be given by mouth or used for gastric 
lavage, since alcohol, although a good solvent for phenol, seems to increase the 
rate of absorption of phenol from the stomach. Thorough gastric lavage with 10 
per cent, solution of glycerin or, if this is not available, with sodium sulphate, 15 
gm. (4 drachms) to the pint of water, should be carried out. 
Nephritis, if it occurs as a complication, should be treated by the standard 
methods employed for this disease. 
It has been shown recently by Meyer218 that a high protein diet given to rats 
increased very definitely their resistance to phenol poisoning. This observation, 
however, probably has no great practical significance in treatment of the poisoning, 
once it has occurred, other than to suggest the use of a high protein diet. 
Vol. IV. 944 CARBON DISULPHIDE 
Nitrobenzene 
Immediate Measures. — In acute poisoning the contaminated clothing should 
be removed at once, and areas of the skin, on which the substance has been spilled, 
should be cleansed with alcohol. Gastric lavage with water containing epsom salt, 
which delays absorption, is performed, although as in phenol, mercury and arsenic 
poisoning the lavage is not of as much value in the industrial case as in that of 
poisoning by ingestion, which is more apt to be seen in private practice. Oils, 
milk and alcohol should not be given by mouth, since they tend to favor absorption. 
Prevention of Respiratory and Circulatory Failure. — Inhalations of carbon 
dioxide, 5 to 7 per cent., in oxygen are indicated for respiratory stimulation and 
coramine, 1.5 c.c., metrazol, gr. i-2 to (0.1 to 0.3 gm.), caffeine sodium benzoate, 
gr. (0.5 gm.), or camphor in oil, 1 to 2 c.c., may be given intramuscularly for 
respiratory and circulatory stimulation. Intravenous infusions of from 5 to 10 per 
cent, glucose in physiological saline solution are indicated, and transfusion of 
blood, 350 to 500 c.c., may be necessary. If acidosis is present, it should be treated 
as described under Methyl Alcohol. Epsom salts, to 1 ounce (15 to 30 gm.), 
usually is to be given orally. 
Hepatic Injury. — Following the acute stage, treatment directed at correction 
of the liver damage may be necessary, and this should follow pretty closely that 
outlined under Tetrachlorethane. If a macrocytic type of anemia develops, liver 
extract, 15 to 30 units per day for the first three or four days and then at intervals 
of from 5 to 10 days, should be given. 
Carbon Disulphide 
Prophylaxis. — The most important point is prevention of such poisoning. 
Preventive measures consist primarily of rigid examination of the plants to insure 
modern, safe equipment and the presence of adequate ventilation. The storage 
and pipe conveyance of carbon disulphide must be satisfactory, and explosions 
should be guarded against. Medical examination of those exposed to this hazard 
should be at intervals not greater than one month. Men should be taught to report 
the first intimation of any unusual symptoms, and if this solvent is the suspected 
cause of the complaints, the employee should be removed at once from the hazard. 
The drinking of alcoholic beverages by those apt to be exposed to carbon disulphide 
should be discouraged. 
Diet. — To date no adequate or specific treatment for cases of chronic carbon 
disulphide poisoning is known. It would seem likely in view of the similarity of 
many of these cases to Korsakoff’s syndrome that a diet high in vitamin content 
with the vitamin B complex as an adjunct would be of value. If vitamin B com- 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: TREATMENT 
plex is to be used, the dosages should be relatively large, e.g., from 50 to 60 mgm. 
of thiamine chloride parenterally daily, 200 mgm. of nicotinic acid daily, 1 mgm. 
of riboflavin three times per day, 20 mgm. vitamin B6 twice daily parenterally 
and so on. Liver extract in dosages similar to those advised in the chapter on 
Manganese might be tried. 
Psychiatric and Ophthalmological Attention. — The aid of a psychiatrist will 
be needed for most of these patients, since a program of mental hygifene will need 
to be instituted. The ophthalmologist should be consulted on problems relating to 
the eyes. 
Exercises for existing muscular weakness, sedation and tonics may be of value. 
If Parkinsonian-like symptoms are present, a trial of those drugs mentioned in the 
section on Mercury for control of these manifestations might be made. 
The acute case will be seen rarely. When such a case does occur, artificial 
respiration, 5 to 7 per cent, carbon dioxide in oxygen inhalations and the respira- 
tory and circulatory stimulants mentioned in the sections on Trichlorethylene and 
Alcohols are to be used. 
Butadiene 
In the manufacture of synthetic rubber the workers are exposed to butadiene 
gas among other substances. No internal disturbance of any type has been noted 
by the writer, but burns of the skin are fairly common. It is significant that fre- 
quently the exposed individual is unaware that his skin has been burned for several 
hours following contact. 
As soon as the worker is aware of, or even suspects, an exposure, he should 
have all clothing removed and then should be placed in a shower bath for a thor- 
ough and prolonged washing of the entire body. This is to be followed by a 
general application of calamine lotion and then fresh clothing worn. 
Radium 
Radium poisoning need never occur, if proper precautions are taken, but these 
precautions must be carried out meticulously, since radium enters the body with 
considerable ease. Necrosis of the bones, anemia and buccal lesions were noted 
in dial workers in the 1924-1925 outbreak of this disease. It was felt at that 
time that the radium entered the body through ingestion, since these workers were 
accustomed to “ point ” their brushes with their mouths. Today radium workers 
are cognizant of this danger and avoid acts which might lead to ingestion of this 
substance. Prevention is directed today against the inhalation of the dust, which 
primarily imposes the obligation of correct hygiene upon plant management. 
In general there are two groups of workers in radium dial manufacture who 
Vol. IV. 944 RADIUM 
must be protected. The first of these are the painters, usually young women. 
These should be provided with individual glass hoods within which the operation 
is performed. The glass protects the worker’s face, especially the breathing zone, 
yet enables a clear vision of the working field. The booth should be exhausted 
by suction ventilation. The head should be covered, the clothing simple and no 
personal articles, such as cosmetics, cigarettes, candy or food, permitted within 
the radium room. 
Rigid personal hygiene must be enforced under supervision and not left to the 
individual’s inclination. An excellent regime has been suggested by Evans68 as 
follows: 
“ The hands must be thoroughly cleaned always before eating or smoking. To 
remove radium paint from the hands Dr. George E. Morris has tested a number 
of solvents. He has found most effective and least toxic a mixture of i part xylene, 
i part trichlorethylene and 2 parts ethyl alcohol. This mixture should be rubbed 
onto the dry skin and removed, before it evaporates, with soap and water. The 
skin then is thoroughly dried and examined in a darkened room under ultra violet 
light, which will reveal any residual luminescent material. If the first cleaning is 
not complete, as is often the case, the entire solvent and washing process is repeated 
until the ultra violet lamp reveals no residual radium paint. In the dark room 
many of the new ultra violet lamp bulbs will be found satisfactory. For example, 
the GE 4 watt RP-i2,36oBL lamp can be obtained in a convenient fixture (Grimes 
Mfg. Co., Urbana, Ohio) including a filter for removing visible light. If a more 
powerful but less portable source is desired, the GE type BH4 (sunlamp with 
filter to remove visible light) may be installed. These new lamps are more suitable 
than the argon glow lamp because the latter gives more visible light and less 
ultra violet radiation. 
“ One wash basin, with solvent, soap, hot and cold water and paper towels 
should be provided for every five workers. A waste receptacle provided with a 
swinging lid operated by a foot pedal should be provided for used towels. In very 
large plants one wash basin per ten to fifteen active workers may suffice, especially 
if rest periods and lunch hours are staggered. The washing and dark room areas 
are most useful if adjacent to one another. Local ventilation should be provided 
in both areas to remove solvent fumes. 
“ A separate sink should be provided for the disposal of contaminated solvents, 
which have been used to wash radium compound from imperfect or discarded 
work.” 
The other group involved in the radium room is that composed of inspectors, 
foreman and those who clean the room. These are exposed likewise to the dust 
and need just as careful supervision in hygiene. 
In order to make certain that the worker is not absorbing too much radium, 
Vol. IV. 944 INDUSTRIAL TOXICOLOGY: PREVENTION 
two routine procedures are in order. One of these is to do a complete blood count 
once a month. The other is to have the worker undergo breath radon measure- 
ments. The reader is referred again to the article by Evans68 for details of this 
measurement. 
In the further prevention of radium absorption it is felt that an adequate 
intake of calcium is of value. This is based upon belief that radium metabolism 
closely parallels that of calcium. On the other hand, if a worker reveals the pres- 
ence within the body of excessive radium, then excretion of radium is aided by a 
low calcium intake. 
In chronic radium poisoning a regime directed towards aiding in the excretion 
of radium should be followed. It is suggested that a low calcium diet, parathyroid 
extract and large doses of ammonium chloride be instituted. That such treatment 
will have much effect is to be questioned. Treatment of any existing anemia is 
also advisable. 
Lead 
Absorption. — Lead enters the body either through the lungs, by ingestion or 
possibly through the broken skin, although this last mentioned route is insignifi- 
cant and industrially not important. Nor does lead poisoning occur frequently 
from ingested lead, whether.the environment be industrial or not. Any acute 
illness attributed to the ingestion of lead deserves a thorough investigation to 
make certain that some other ingredient was not the actual cause of the illness. 
In 1930 Kehoe159a placed two students upon a prolonged regimen of increasing 
oral doses of soluble lead, one receiving 2 mgm. for a period of 6 months, the other 
1 mgm. for a period of 30 months. His study included laboratory data of the 
microscopic blood smears, excretory response and changes in the level of lead con- 
centrations in the blood and urine. Neither subject studied revealed any symp- 
toms of plumbism. Occasionally a clinician reports plumbism from ingested lead, 
in which the study has been so scientifically thorough as to accept such instances 
as authentic, as in the report of Magnuson and Raulston195a. The men they ob- 
served had been in the habit of holding in their mouths roofing nails, which were 
fourteen gauge “hot dip” galvanized nails containing lead from 0.9 to 4.7 per 
cent, in the zinc coating. 
Except for the exceedingly rare case, then, it is the inhalation of lead fumes 
or dust, which causes lead intoxication, and almost invariably it is from the fumes, 
since the fumes are less conspicuous, whereas a dusty atmosphere immediately 
bespeaks bad housekeeping and is more apt to lead to steps for its eradication. 
However, the worst case of lead intoxication ever seen by one of us (Johnstone) 
was that of lead encephalitis due to prolonged exposure to heavy concentrations 
of lead dust. 
Vol. IV. 445 LEAD 
Storage. — The eventual fate of lead once it has entered through the lungs to 
reach the circulating blood is a controversial question, too involved for detailed 
discussion here. The opinions of various investigators have been reviewed else- 
where156. Following the original work of Aub and his co-workers4b’5,6, it has 
been generally believed that lead was transported as finely divided colloidal lead 
phosphate to be deposited as a tertiary lead phosphate in the bones. Subse- 
quently Aub, Robb and Rossmeisl6a stated that most of the lead was stored in 
the trabeculae, not the cortex of the bone. They contended that, since the 
trabeculae act as a storehouse for calcium, the lead stored here was mobilized or 
freed according to calcium metabolism. This opinion introduced the popular 
calcium therapy about which more will be mentioned later. To Kehoe and 
Thamann160a the idea that lead is fixed in stable form in the skeleton, either 
normally or through any kind of therapy, is untenable. For practical purposes 
suffice it to state that it is the accumulation of lead within the blood and 
tissues of the body which causes symptoms of lead intoxication; that following 
the withdrawal of the patient from his exposure, lead is excreted in sufficient 
amounts as to permit the subsidence of symptoms. If certain amounts of lead 
are actually stored in the bones or elsewhere, it has little subsequent effect upon 
the individual. 
Because the treatment of lead intoxication is intimately related to the ques- 
tion of storage and elimination, further consideration of these factors will be 
entertained in the discussion of the treatment of plumbism. 
Prophylaxis. — As with all cases of occupational intoxication that from lead 
is unwarranted. Infrequent in the larger, well supervised plants, these cases 
occur usually in small plants where the principles of industrial hygiene are ignored. 
In addition to the following measures suggested for routine plant adherence it 
would be well for exposed workers to drink adequate amounts of milk daily and 
to maintain good intestinal elimination. By all means constipation is to be 
avoided in lead workers. 
The best method to avoid lead poisoning is, of course, to take measures to pre- 
vent it. To this end Gant853, suggests the following rules and mechanical features: 
1. Hoods with adequate exhaust ventilation to be at any point where dust 
or fumes arise. 
2. All mixing and shaking to be done in enclosed machines. 
3. All powdered compounds to be transferred by means of adequate vacuum 
lines. 
4. Work tables to be provided with grated tops, ventilated from below, and 
equipped with small narrow troughs filled with water and attached to 
each side to prevent dust falling to the floor. 
5. All inlets to exhaust ventilating ducts to be below the level of the nose as 
far as possible to prevent fine dust particles from being inhaled. INDUSTRIAL TOXICOLOGY: PREVENTION 
6. A chemical analysis of samples of air from various parts of the plant to be 
made at different intervals during working hours. Any spot showing 
more than 1.5 mgm. of lead per 10 cu. m. is a potential health hazard. 
7. Employees in hazardous spots as found under “6” to wear respirators. 
Where movements are confined to a small area, forced-draft respirators, 
fresh air from the outside, to be used. If exposure is to fumes, masks to 
be provided with canisters charged with activated carbon. Respirators 
are only from 70 to 90 per cent, efficient and must be inspected and 
changed frequently. 
8. No dust allowed to accumulate on the floor. 
9. Floors to be wet at frequent intervals and powdered compounds used, if 
possible. 
10. All cleaning to be done with large vacuum lines. No sweeping. 
11. To prevent the collection of dust on rafters, sills, etc. ventilating ducts 
to be installed, equipped with dust-filters near the ceiling or in mid-air. 
12. To avoid the contamination of outside air and surrounding territory and 
as an economy measure electrostatic precipitators to be installed in the 
stacks and flues. 
13. The personal hygiene of the employees to be closely guarded. Locker 
rooms with showers, a lunch room isolated from the plant and a change of 
overalls twice a day to be provided. Hands and face to be washed before 
eating. No eating, chewing or smoking during working hours. 
Treatment. — Before having the reader become involved in the arguments 
supported by the various investigators in this field regarding the basis for treat- 
ment of lead intoxication, the author of this portion of the text wishes to describe 
a very simple and workable regime used at the Golden State Hospital in Los 
Angeles. Since this is an industrial clinic, to which come all types of occupational 
diseases, the incidence of true plumbism is considerable. Since 1936, when the 
author became affiliated with this clinic, until 1941 there were admitted annually 
for treatment an average of 54 patients. This took a sharp upturn following the 
war and during the first ten months of 1944 113 cases were seen. From 1936 until 
1939 the treatment followed in general the teachings of Aub. Since then that 
regime has been abandoned in favor of the following method: 
1. All patients with proven plumbism are withdrawn immediately from their 
occupational exposure. Even if the clinical and laboratory findings indicate 
a questionable or borderline case, the worker is transferred to a type of 
work involving no exposure to lead. 
2. In those cases with mild intestinal colic calcium is given by mouth, good 
intestinal elimination encouraged and the patient advised to continue to 
work. 
3. In cases of severe intestinal colic the patient is hospitalized and intravenous 
Vol. IV. 445 LEAD 
calcium therapy instituted. This is continued until the more violent colic 
has subsided at which time calcium by mouth is given. All calcium therapy 
is stopped upon the cessation of intestinal discomfort. 
4. To the general hospital diet 20 minims of viosterol daily is added. 
5. For the anemia, which invariably is present in the severe cases, ferrous 
sulphate is prescribed. 
Under this regime we have not found it necessary to resort to morphine, 
atropine sulphate, nitroglycerin or amyl nitrite, all of which are referred to in 
the subsequent review of the methods of treatment. 
The success of the treatment just outlined indicates that the symptoms from 
lead intoxication subside because (1) the patient has been withdrawn from his 
exposure, thus preventing any further accumulation of the noxious substance, 
and (2) he rapidly eliminates the lead from his body. One case in particular is of 
interest in this regard. A patient with a severe degree of lead encephalitis was 
relieved of his nervous and cerebral symptoms by two spinal fluid taps. He re- 
ceived no calcium and recovered completely. Since his lead intoxication he has 
had pneumonia on one occasion and on another a septicemia without any evidence 
of exacerbation of his so-called “stored lead ”. 
The almost instantaneous relief of lead colic following the use of calcium leaves 
little doubt that this drug has a physiological effect upon the smooth muscle of 
the intestinal tract, but the action is too sudden and dramatic to cause anyone 
to believe that the quick relief is due to the immediate storage of lead within the 
bones of the body. It is our considered opinion that once the calcium has caused 
the colic to cease, its utility is ended. 
As promised in the opening paragraph under treatment the following opinions 
held regarding the treatment of lead intoxication now will be outlined. 
Deleading by High Calcium Diet: Following the work of Aub, Fairhall, Minot 
and'Reznikoff5, which indicated that lead could be either stored or excreted by 
distorting the calcium metabolism, therapy was directed along these lines. The 
conclusions drawn from their work were that a negative calcium balance increases 
the rate of lead excretion, while a positive calcium balance favors the storage of 
lead. To this end then the treatment for the acute episode in the past consisted 
of the following: 
1. A high calcium diet, which includes much milk, green vegetables and 
potatoes. 
2. The administration of calcium products and vitamin D orally, e.g., calcium 
lactate, i drachm (4 gm.), once every two hours, or calcium gluconate, 
grains (0.5 gm.), in milk at three-hour intervals, so that the patient 
obtains five or six doses daily. 
3. Calcium gluconate, 10 c.c. of 10 per cent, solution, intravenously daily for 
five days. 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PREVENTION 
4. Magnesium sulphate, ounce every morning, to sweep out the relaxed 
bowel. 
5. As substitutes for the intravenous calcium gluconate in the relieving of 
abdominal pain, hypodermic injections of morphine sulphate, 5 grain (15 
mgm.), and atropine sulphate, yjyo grain (0.6 mgm.); nitroglycerin, from 
one to two grain (0.6 mgm.) tablets dissolved under the tongue or the 
inhalation of the contents of a 5-minim (0.32 c.c.) amyl nitrite pearl. 
Disadvantages of Method. — Recently much doubt has been thrown on this 
method of treatment by the work of Lederer and Bing180e. Their work indicated 
that the deposition of lead in the bones of growing animals is retarded by increas- 
ing the calcium content of the diet, and that the phosphorus content of the diet 
had no significant effect on the amount of lead deposited in the bones. This would 
indicate then that a high calcium diet would be the optimum diet for deleading 
rather than for the deposition of lead in the bones. The use of the high calcium 
diet according to this view might actually be dangerous by mobilizing lead for 
possible storage in the central nervous system in the acutely ill patient. Taeger3060 
arrives at such a conclusion and advises against large doses as well as against the 
intravenous administration of calcium. Shelling and Hopper286b believed the use 
of calcium did not induce superior calcification but rather had the opposite effect, 
especially when the phosphorus intake was inadequate. Kehoe and Thamann160* 
were of the opinion that the use of agents to promote the quick release of lead 
from the tissues was hazardous. Shelling28611 demonstrated experimentally that 
the addition of calcium carbonate to an optimal stock diet containing lead car- 
bonate fed to rats resulted in an increased toxicity. These rats evidenced toxicity 
and died sooner than the rats fed on the same stock diet to which sodium phos- 
phate had been added. Gray and Greenfield960 reported a small series of cases, 
where prolonged administration of high calcium diet therapy was responsible for 
permanent, irreparable damage to the nervous system. They concluded that a 
high calcium regimen was the best means of deleading. In view of this evidence 
the advisability of the use of high calcium diet alone is open to question. The 
frequently dramatic relief of abdominal pain obtained from the intravenous ad- 
ministration of calcium may represent, then, only a general depressant action of 
calcium on smooth muscle rather than a specific reaction as regards the lead in 
the bloodstream. 
Optimal Calcium Diet with High Phosphorus and High Vitamin. — Gray and 
Greenfield960 found the use of an optimal calcium diet with a high phosphorus and 
high vitamin diet, particularly D, the best treatment in these cases. With this 
regimen an essential element was the administration of sodium phosphate, two 
drachms (8 gm.), three times daily. Shelling28611 indicated that in order to de- 
posit lead in the skeleton as an insoluble lead phosphate a certain amount of 
phosphate was required, and thus when phosphate was inadequate, free lead 
Vol. IV. 445 LEAD 
might remain in circulation. He stated that the addition of sodium phosphate 
“provides sufficient phosphate for the deposition of both calcium and lead phos- 
phosin the skeleton, for the excretion of lead as the relatively non-toxic lead 
phatephate and also for the formation of colloidal lead phosphate in the blood.” 
As indicated, the work of Lederer and Bing180e directly opposes this statement 
and seems to indicate that the addition of phosphate had no significant effect. 
The work of Lederer and Bing180e further indicated that the beneficial effect of 
calcium in the diet in retarding the retention of lead by the body was due to re- 
actions which occurred in the intestinal tract, and that calcium carbonate orally 
was the most valuable preparation. 
Deleading by Low Calcium Diet with High Phosphorus. — In the past a regimen 
of a low calcium high phosphorus diet, phosphoric acid and magnesium sulphate 
had been used successfully by Gray96b in deleading treatment. 
He also elaborated a similar diet with a calcium to phosphorus ratio of 1:4. 
To these were added 20 minims of viosterol (250 D) daily, since vitamin D was 
deficient in the diet. Previously he had used a low calcium diet consisting of 
meat, liver, potato, rice, tomatoes (cooked without milk), canned corn, bananas, 
apples (peeled), tea, coffee (without milk), butterfat, bread (prepared without 
milk, such as salt-free nephritic bread or sodium bicarbonate biscuits or crackers), 
sugar, salt and pepper. Phosphoric acid in amounts of from 10 c.c. every two 
hours for six doses daily to 10 c.c. once every hour for ten doses daily was used. 
In addition, magnesium sulphate, \ ounce (15 gm.), was given each morning. 
With this regimen, increase in urinary lead was seen at first, and this was followed 
by a decrease as the patient was, presumably, deleaded. 
Other Methods. — Other methods suggested for deleading have included the 
low calcium diet cited above, ammonium chloride, 15 grains (1 gm.), every hour 
for ten doses daily and magnesium sulphate, \ ounce (15 gm.), every morning. 
Belknap12d’12e used 15 drops of potassium iodide twice daily or 7 drops of sodium 
iodide twice daily both in saturated solution. Sodium bicarbonate, from 5 to 
8 drachms (20 to 30 gm.), daily, divided into five or six portions, has been used 
also as has parathyroid extract. 
Advisability of Deleading. — As indicated above there is disagreement concern- 
ing the possibility of deposition of lead in bones by changes in diet or by medica- 
tion. In addition, the advisability as well as the possibility and the methods of 
deleading is distinctly open to question. Most authorities feel that it should not 
be attempted before from three to four weeks have elapsed after the acute episode. 
Most feel that the deleading should be carried out only in the hospital and with 
adequate laboratory checks, although Belknap12d, cited above, deleads patients 
in mild cases while they are ambulatory but under close supervision. He re- 
quires a blood level of 80 per cent, hemoglobin, 4,000,000 or more red blood cells, 
stippled cells not more than from 1,000 to 5,000 per million red blood cells for two 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PREVENTION 
to three weeks and a twenty-four-hour urine lead 0.15 mgm. or lower before 
undertaking the deleading. He also deleads no oftener than once in four weeks and 
preferably not oftener than once in six or eight weeks. 
Benefits versus Drawbacks of Deleading. — Those who oppose deleading feel 
that the danger of producing lead encephalopathy is too great, and that at any 
rate the patient cannot be “deleaded” successfully. Those who favor it urge 
that the stored lead represents a constant potential hazard, since acute episodes 
such as infections with acidosis or other periods of metabolic stress may cause 
deleading at an undesirable time. Aub4“ feels that thorough deleading approxi- 
mately halves the period of disability for lead palsies. 
Ascorbic Acid Therapy. — A few investigators, notably Holmes, Campbell 
and Amberg140a, have contended that daily administration of ascorbic acid is of 
benefit in treating lead intoxication. Most investigators, hovfever, have found this 
adjunct to have negative results. The Cincinnati group at the Kettering Insti- 
tute6715 during their study of nutrition of industrial workmen found ascorbic acid 
deficient in a majority, and in lead workers it was below the average, but they found 
also that the administration of ascorbic acid had negative results in plumbism. 
Treatment in Lead Palsy. — In this condition stretching of fibers of paretic 
muscles should be prevented. In those cases presenting a wrist-drop a cocked-up 
splint to include the fingers and worn night and day is used until function returns. 
Hot-water baths (no° F.), electric stimulation by interrupted galvanic current 
and gentle massage, preferably by whirlpool, once every day or two are used. 
Strenuous massage and violent exercise are avoided. Reeducation exercises are 
of value. 
Treatment in Lead Encephalopathy. — Encephalopathy is rare and has been 
seen only once in our clinic in the past five years. When it does occur, lumbar 
puncture and sedation may be required. Magnesium sulphate, 2 c.c. of a 25 per 
cent, solution, given intramuscularly for every four to six hours, and barbitu- 
rates are used. For convulsions barbiturates, e.g., sodium amytal, from 35 to 
grains (0.23 to 0.5 gm.), are given intravenously, and avertin is used rectally. 
Suboccipital or subtemporal decompression in lead encephalopathy has been used 
successfully. 
In conclusion, despite the expression of opinions just presented, it is the 
author’s opinion that the treatment of lead intoxication requires therapy for the 
acute condition only. Attempts to store lead or to delead a patient are unneces- 
sary and may be, in the case of deleading, dangerous. 
Carbon Monoxide 
Treatment. — Acute Anoxemia. — When this occurs, the victim should be 
removed immediately from his exposure and artificial respiration begun by the 
Vol. IV. 445 HYDROGEN SULPHIDE 
Schaefer prone pressure method of resuscitation. It is extremely important, how- 
ever, that inhalations of 5, 7 or 10 per cent, carbon dioxide in oxygen be started 
early and continued for 15 to 30 minutes or even longer to obtain deep breathing. 
The carbon dioxide not only increases the volume of breathing but also aids in the 
disassociation of carbon monoxide from the hemoglobin. The inhalations should 
be increased to the point where full, deep inspirations are obtained from the pa- 
tient. All emergency squads, which are called frequently to attend such cases, 
should be equipped with this carbon dioxide and oxygen mixture with inhalation 
apparatus for its administration. If such apparatus is immediately available, 
the patient should be kept warm with blankets and hot-water bottles and treated 
at the spot rather than be moved to the hospital with attendant delay in the ad- 
ministration of the inhalations. It should be remembered that probably half 
of the carbon monoxide is eliminated from the body during the first hour after 
removal from the exposure, and consequently long-continued administration of 
the carbon dioxide and oxygen may not be required. If such inhalations are not 
available, the patient should be transported to a hospital, where they can be 
obtained, and en route it is necessary to continue the artificial respiration. 
Koch164a recommended blood transfusions preceded by venesection in severely 
acute cases. He pointed out that the chief effect of carbon monoxide poisoning 
was the anoxemia, and therefore, the hemoglobin introduced by means of the 
blood transfusion will act at once as an oxygen vehicle. 
Methylene blue, once thought to be an antidote, is not of value and is now 
thought to be harmful. With the possible exception of caffeine, it is felt that 
the use of drugs is ineffectual, if not actually harmful. Strychnine, camphorated 
oil, digitalis, pituitary extract, adrenalin, alpha-lobeline and morphine fall into 
this category. 
The use of 12 ounces (350 c.c.) of physiological solution of sodium chloride 
given by rectum every four hours during the first few days has been suggested, 
as has the rectal administration of a 4 per cent, sodium bicarbonate solution. 
Hydrogen Sulphide 
Prevention. — Whenever it is known that this substance is apt to be present 
in any industrial process, workmen should be forced to wear specially designed 
protective masks to prevent inhalation of the gas. The eyes likewise should be 
protected against irritation. All processes should be conducted under adequate 
exhaust conditions. 
Treatment. — Combating Respiratory Failure. — In severe poisoning chief at- 
tention is directed to the respiratory failure, which appears to be due to depres- 
sion of the respiratory center. The patient should be moved at once from the 
point of contact with the gas and fresh air provided. Artificial respiration should 
VOL. IV. 445 INDUSTRIAL TOXICOLOGY: PREVENTION 
be started at once, and as soon as available inhalations of mixtures of from 5 to 7 
per cent, carbon dioxide with oxygen are to be commenced. The use of respiratory 
stimulants, such as caffeine sodium benzoate, grains (0.5 gm.), coramine, 0.5 
c.c., intramuscularly or preferably intravenously, and metrazol, grains (0.1 
gm.), may be of value, but it is questionable if these are of value in severe cases 
unless adequate respiration has been established by artificial respiration or by the 
oxygen-carbon dioxide inhalations. Bronchitis and bronchopneumonia may ap- 
pear as complications and require the ordinary treatments for these conditions. 
Care of Eyes. — The eyes may be severely irritated, and the condition may 
even go on to the development of corneal ulcers. As with other irritants to the 
eyes, e.g., ammonia, they should be thoroughly washed at once with water. Fol- 
lowing this, the use of a saturated boric acid solution and of olive oil is advised. 
Local anesthetic solutions such as 2 per cent, butyn or 0.5 per cent, pontocaine 
hydrochloride may be used in relief of pain. Continuous warm boric compresses 
may be of value in preventing further complications. When available, the advice 
of an ophthalmologist should be sought. 
The Petroleum Distillates 
Treatment. — Acute. — Invariably these .cases are acute, and the treatment 
must be designed to prevent respiratory and circulatory collapse. When the 
exposure has been intense, pulmonary edema and alveolar damage may be ex- 
pected early. For such conditions positive pressure therapy is the method of 
choice. The clearing of the edema and the rapid recovery in these and in edema 
from other pulmonary irritants is so startling as to consider this type of treat- 
ment almost specific. 
If positive pressure cannot be induced, then oxygen by catheter, mask or tent 
should be resorted to early. If the mask is used without positive pressure, the 
development of negative pressure resulting from the collapsing rubber bag must 
be avoided. 
Positive pressure respiration is urged, and the positive pressure should be from 
2 to 6 cm. of water. A mask of the meter type (see section on Inhalation Therapy) 
can be used with resistance provided at the end of expiration. By this method 
positive pressure may be obtained by exhaling through a constricted orifice. 
Barach advises that the patient be subjected to a pressure of 4 cm. of water until 
signs of edema clear, after which the pressure may be lowered gradually. 
If the patient’s clothing is saturated with these noxious substances, these 
should be removed and the body cleansed and dried. The patient should be 
wrapped in blankets and kept warm. At this time circulatory failure, if present, 
should be treated by any of the following drugs, coramine, 1.5 c.c., caffeine 
sodium benzoate, grains (0.5 gm.), or metrazol to grains (0.1 to 0.3 gm.) 
Vol. IV. 445 OXYGEN THERAPY 
intramuscularly. The coramine and metrazol may be used intravenously and will 
also act as respiratory stimulants. Artificial respiration usually is felt to be con- 
traindicated because of the existing lung damage, and adrenalin administration 
has been found to give poor results. 
Prevention of Pulmonary Complications. — The lungs especially need to be 
watched for complications, such as bronchopneumonia. After the first portion 
of the acute stage, where respiratory stimulation chiefly is needed, oxygen therapy 
may be substituted for the carbon dioxide and oxygen inhalations. For cough 
codeine phosphate or sulphate, % to 1 grain (30 to 60 mgm.), perhaps in a cough- 
syrup vehicle, is useful. 
Nervousness and Restlessness. — These conditions may require sedation by any 
of the following drugs; chloral hydrate, 10 to 30 grains (0.6 to 2.0 gm.), pheno- 
barbital, grains (0.1 gm.), sodium bromide, 10 to 30 grains (0.6 to 2.0 gm.), or 
paraldehyde, 2 to 4 drachms (8 to 16 c.c.). The paraldehyde may be mixed with 
elixir lactate pepsin, poured over crushed ice and administered by mouth, or it 
may be given rectally in olive oil with 1.5 c.c. benzyl alcohol. Magnesium 
sulphate, 1 ounce (30 gm.), should be given. 
Venesection followed by blood transfusions to rid the body of methemoglobin 
has been advocated. When ingestion of the substance has occurred, lavage with 
magnesium sulphate solution is of value. 
Conjunctivitis. — Due to irritation from petroleum distillate fumes, conjunc- 
tivitis may be treated by dropping 1:1,000 adrenalin solution into the eyes four 
times a day, followed by the use of cold applications for from 10 to 15 minutes. 
Bland boric acid ophthalmic ointment should be used also. 
Chronic Cases. — Patients in chronic cases chiefly need removal from their 
exposure. The diet should be high in calories with added vitamin preparations. 
For the secondary anemia ferrous sulphate, 5 grains (0.3 gm.), two tablets three 
times a day, may be used. The ferrous sulphate preparations seem effective in 
relatively small doses, and they also seem to cause less gastrointestinal discomfort 
than other iron compounds. 
Oxygen Therapy in the Acute Occupational Intoxications 
Although the physical and chemical characteristics of the various gases have 
been studied for many decades, their therapeutic application did not occur until 
after the investigations of Van Slyke, Haldane, Boothby, Barcroft, Henderson, 
Haggard, Barach and a few others. Barach9c in particular has demonstrated 
the value of oxygen, carbon dioxide and sometimes, helium in the treatment of 
cardiac failure, coronary artery disease, pneumonia, pulmonary edema, emphy- 
sema, atelectasis and asthma. While general medicine has accepted this type of 
therapy, industrial medicine has not utilized it to the degree warranted. 
VOL. IV. 445 INDUSTRIAL TOXICOLOGY: PREVENTION 
Following an undue exposure to certain industrial chemicals, the pathology 
found in the lungs is not dissimilar from that found in various respiratory and 
cardiac diseases of non-occupational origin. In these latter conditions the oxygen 
want is due to the inability of the lungs to diffuse oxygen or the heart to circulate 
oxygen in the blood. This is true likewise of the industrial agents, which may act 
as an asphyxiant, as an irritant to the lungs or as an anesthetic to the respira- 
tory center in the brain. Regardless of the manner of action, the result is anox- 
emia. It is to combat this anoxemia that oxygen therapy is of value. When 
resorted to, oxygen enriched atmospheres containing 40 to 60 per cent, oxygen will 
raise the oxygen saturation of arterial blood to near normal levels. 
Carbon dioxide likewise is a common therapeutic agent. Ever since Haldane, 
Priestley and Douglas contended that the volume of breathing is controlled by 
the percentages of carbon dioxide in the air within the lungs, percentages of this 
gas have been employed to stimulate respirations. Yet, if the writer interprets 
the observations of Barach correctly, the general use of carbon dioxide is not 
only of questionable value in many instances but likely to be harmful. Barach 
and his co-workers would discourage its use in the treatment of most cardiac and 
respiratory diseases except for post-operative atelectasis, hiccoughs and acci- 
dental asphyxia. 
In Barach’s recent excellent book9c he gives but scant space to the treatment 
of the occupational disturbances of the lungs. Yet it has been the writer’s 
experience that oxygen therapy is of great value in immediate treatment of the 
acute effects from undue exposure to sulphur dioxide, phenol, ammonia, nitric 
acid and nitrous fumes and cadmium. All of these are capable of producing a 
marked pulmonary edema. Carlisle33 likewise found that oxygen gave striking 
results in the treatment of pulmonary edema due to chlorine and nitric acid. 
Broadly, the chemical agents used in industry which may affect the respiratory 
system are: 
1. The irritants: The most common of these are chlorine, bromine, ammonia, 
nitrous fumes, chloropicrin, phosgene, diphosgene, sulphur dioxide and cadmium. 
Exposure to high concentrations of these may result in pulmonary edema, bron- 
chiospasm, bronchiopneumonia and concentration of blood in the pulmonary 
vessels. 
2. The asphyxiants: These are primarily carbon monoxide, cyanide and hy- 
drogen sulphide. With carbon monoxide asphyxia is produced by the displacement 
of oxygen within the blood by the noxious gas. Therefore, the more quickly the 
disassociation is attacked, and the normal relationship of oxygen to hemoglobin 
takes place, the less permanent damage will occur. It is in this type of case that 
carbon dioxide should be combined with oxygen in amounts of 5, 7 or 10 per cent. 
The carbon dioxide stimulates the respiratory center to produce full, deep respira- 
tions and thus relieves the anoxemia. 
Vol. IV. 445 OXYGEN THERAPY 
Recently the investigations of End and Long66a indicate that pure oxygen under 
pressure is of greater value than is the carbon dioxide oxygen mixture. By animal 
experimentation they show that carbon monoxide causes tissue damage by pro- 
ducing an anoxia, and that current methods of treatment are unable to correct 
this anoxia. Inhalation of oxygen under three atmospheres of pressure is capable 
of preventing such anoxia by causing solution of enough oxygen in the blood to 
provide for the needs of the tissues. Inhalation of oxygen under three atmos- 
pheres of pressure for several hours is safe. 
The first action of hydrogen sulphide is upon the respiratory center. In a per- 
son overcome by these fumes respirations will cease before the heart action stops. 
It is, therefore, imperative to stimulate the respiratory center by carbon dioxide- 
oxygen and/or by artificial respiration. 
Oxygen is of little or no value in cyanide poisoning, since cyanide, instead of 
combining with the hemoglobin in the blood stream, retards oxidation in the tissue 
cells. 
3. The anesthetics: A large group of solvents used in industry gives off vapors 
which affect the central nervous system by producing an anesthesia. Of these the 
most common are carbon tetrachloride, trichlorethylene and the petroleum dis- 
tillates. In the average case these do not cause any pathological change within 
the lungs proper, although the petroleum distillates have been known to cause 
pulmonary edema and one of us (Johnstone156) had a case in which pleural effusion 
resulted after a massive dosage of gasoline. Just as in operative anesthesia an over- 
dosage of these gases produces unconsciousness which demands immediate oxygen 
therapy. 
It should be pointed out to the reader that in cases of pulmonary edema from 
any cause, occupational or non-occupational, the mere utilization of oxygen is not 
sufficient. The best results are obtained only if oxygen is administered under 
positive pressure. While all physicians are acquainted with the nasal catheter, 
various masks, oxygen tents and oxygen rooms, the apparatus for positive pres- 
sure needs explanation: 
“The oxygen-injector mask metered for positive pressure is designed 
solely for the treatment of pulmonary edema dud to cardiorespiratory illness 
or gas poisoning. It should be employed cautiously in patients with shock 
(Barach9c). 
“The injector mask has been equipped with a metal disk that surrounds 
the expiratory flutter valve and contains on its surface five orifices of varying 
diameters. Expiration proceeds naturally without pressure when the largest 
orifice is employed. When the disk is turned to progressively smaller orifices, 
the patient exhales under a positive pressure which is i, 2, 3 or 4 cm. of water, 
depending upon the size of the orifice. These pressures have been recorded 
during quiet breathing and would be higher in dyspneic patients. It will be 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY: PREVENTION 
found that expiration at a pressure of 4 cm. of water is uncomfortable and can 
be used for short periods only. However, a swifter clearance of pulmonary 
edema, especially in chlorine and nitric acid gas poisoning, may be obtained, 
when the higher pressures are used for short periods. In pulmonary edema 
taking place during the course of clinical illness 3 cm. of water may be adequate 
to result in a disappearance of the signs of moisture in the lungs, and a smaller 
pressure of 1 to 2 cm. of water then may be used for periods of one to three 
hours as may be required. Return of signs of moisture in the lungs indicates 
reapplication of positive-pressure breathing. 
“In order to employ 100 per cent, oxygen a high liter flow such as 12 to 
* 15 liters per minute is necessary to prevent collapse of the collecting bag. 
Under these circumstances it is desirable for the injector to be one-third full of 
water so that the oxygen may pick up some moisture as it passes through. 
Test of the relative humidity of 100 per cent, oxygen passing over the water 
surface in the injector has shown a relative humidity of 20 per cent, of the air 
entering the mask. However, it has also been demonstrated that additional 
moisture is contributed to the inspired air, because the inner surface of the 
mask is itself wet with moisture, which has condensed on it from the expired 
air, and the actual relative humidity of air entering the mask under these 
circumstances is 40 per cent. If a higher relative humidity is desired during 
the inhalation of 100 per cent, oxygen, either with or without positive pressure, 
the injector may be removed and a water bottle attached to the regulator. 
The oxygen then passes through 2 or 3 inches of water and possesses a higher 
relative humidity. 
“The patient may be treated with 50 or 60 per cent, oxygen and the positive 
pressure desired by setting the injector and pressure dials at the appropriate 
orifices. This results in considerable saving of oxygen and is a therapeutically 
effective, efficient and practical procedure. Although a swifter clearance of 
edema of the lungs may be obtained by expiratiqn at high pressures, it is 
frequently desirable to employ lower pressures, such as 2 to 3 cm. of water, 
even though a longer time is necessary for complete clearance of the signs of 
edema. This is in part because of lessened discomfort to the patient but also 
because low pressures do not significantly retard the entrance of blood into 
the right heart. In patients with cardiac illness such as congestive heart 
failure, the retardation of blood is comparable to tourniquetting the extrem- 
ity and facilitates the recovery of the heart muscle by making it possible for 
the heart to work on a smaller volume of blood. 
“However, in patients with peripheral circulatory failure, pressures of 
i cm. of water may be employed in the attempt to eliminate pulmonary edema 
without causing any significant decrease in return of blood from the right 
heart. The systolic blood pressure should be carefully recorded at io-minute 
Vol. IV. 445 OXYGEN THERAPY 
intervals in all patients with shock. When pulmonary edema has cleared, the 
patient may breathe 60 to ioo per cent, oxygen without pressure. If no re- 
currence of edema takes place, and the patient is clinically better, the injector 
may be turned to 50 per cent, oxygen and then to 40 per cent., and the mask 
may be finally removed, when the clinical condition of the patient indicates 
that he is out of danger. If pulmonary edema recurs after termination of posi- 
tive pressure, the pressure should be applied again at 3 cm. of water and then 
gradually lowered at longer intervals.” 
It is hoped that this rather concise discussion of oxygen therapy will focus the 
attention of the industrial physician upon an exceedingly valuable and often life- 
saving aid in the treatment of respiratory affections due to the inhalation of cer- 
tain noxious vapors or fumes. Too frequently workers, who are overcome by such 
agents, are given ineffectual smelling salts, hypodermics of indiscriminate medica- 
tion or are subjected to an interim of neglect while awaiting transportation to a 
hospital. Nor is hospitalization always assurance that oxygen therapy will be 
instituted upon the patient’s arrival, since the pathology of the occupational 
respiratory affections is not too well known by the attendant staff of the average 
non-industrial hospital. The industrial physician would do well to specify the 
type of treatment he desires when referring cases to such institutions. 
Vol. IV. 445 INDUSTRIAL TOXICOLOGY 
Part III 
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April 1, 1945- 
Vol. IV. 445 INDEX 
Acetates, 630 * 
Acetones, 630 
Acetylene, 634 
welders and, 634 
Acids, inorganic, 604 
Acrolein, 631 
Acrylonitrile, 627 
Age in relation to susceptibility, 603 
Alcohol ethers, treatment of, 663 (35) 
Alcohols, 629, 663 (35) 
methyl, 629 
treatment of, 663 (35) 
Aldehydes, 631 
acetaldehydes, 631 
acrolein, 631 
allylaldehyde, 631 
croton aldehyde, 631 
formaldehyde, 631 
paraldehyde, 631 
Aliphatic or petroleum solvents, 629, 
663 (29) 
acetates, 630 
acetones, 630 
acetylene, 634 
acrolein, 631 
alcohol ethers, 663 (35) 
alcohols, 629, 663 (35) 
treatment of, 663 (35) 
bromine compounds of the hydrocar- 
bons, 647 
carbitol, 632 
carbontetrachloride, 636, 663 (29) 
prophylaxis of, 663 (30) 
treatment of, 663 (29) 
cellosolves, 631, 632 
chlorinated hydrocarbons, 635, 663 
(31) 
carbon tetrachloride, 636 
ethylene chlorhydrin, 645 
ethylene dichloride, 643, 663 (34) 
treatment of, 663 (34) 
hexachlorethane, 644 
methyl chloride, 644, 663 (33) 
treatment of, 663 (33) 
monochlormethane, 644 
Aliphatic or petroleum solvents (cont.)’. 
chlorinated hydrocarbons (cont.): 
pentachlorethane, 644 
saturated, 635 
tetrachlorethane, 643, 663 (32) 
treatment of, 663 (32) 
tetrachlorethylene, 642, 663 (32) 
treatment of, 663 (32) 
tetrachlormethane, 635, 663 (33) 
treatment of, 663 (33) 
trichlorethylene, 639, 663 (31) 
prophylaxis of, 663 (31) 
treatment of, 663 (31) 
unsaturated, 635 
chlorinated naphthalenes, 645, 663 
(34) 
prophylaxis of, 663 (34) 
treatment of, 663 (35) 
diethylene dioxide, 633 
dioxan, 631, 633 
ether, 633 
formaldehyde, 631 
furfural, 633 
glycols, 631 
halowax, 645 
hexamethylenetetramine, 634 
ketones, 630 
methyl cellosolve, 632 
metol, 634 
nitroglycerine, 634 
oxalic acid, 634 
Alkalies, 609 
American Standards Association, 608 
Ammonia, 610, 663 (17) 
treatment of, 663 (17) 
Aniline: Nitrobenzenes: Nitrotoluenes, 
567, 663 (1) 
blood in, 658 
urine in, 758 
Aniline dyes, 663 (1) 
Aniline tumors of the bladder, 663 
diagnosis of, 664 
incidence of, 663 
Antimony, 620 
Argyria, 621 
1 2 
INDEX 
Aromatic or benzene series of solvents, 
648 
alphadinitrophenol, 659 
aniline, 657 
blood in, 658 
urine in, 658 
aniline dyes, 663 (1) 
aniline tumors of the bladder, 663 
diagnosis of, 664 
incidence of, 663 
benzene, chlor compounds of, 662 
benzene derivatives, 656, 663 (37) 
prophylaxis of, 663 (37) 
treatment of, 663 (38) 
benzol: see coal tar benzene, 648, 663 
(37) 
betanaphthylamine, 660 
chlor compounds of benzene, 662 
chlorotoluidine, 660 
coal tar benzene, 648, 663 (37) 
blood in, 649, 650 
diagnosis of, 650 
newer knowledge of, 562 
prophylaxis of, 663 (37) 
treatment of, 663 (37) 
dimethylbenzene, 654 
dinitrocresol, 660 
dinitrophenol, 659 
diphenyls, 662 
DNB, 658 
DNT, 658 
methyl benzene, 654 
nitroanilins, 660 
nitrobenzenes, 657 
nitrochlor, 662 
nitrotoluenes, 657 
paraphenylenediamine, 660 
tetryl, 662 
TNT, 658, 661 
toluene, 654 
toluol, 654 
trinitrophenylmethylnitramine, 662 
trinitrotoluene, 661 
xylene, 654 
xylol, 654 
Arsenic, 621, 663 (22) 
nervous system changes from, 623 
skin lesions from, 622 
treatment of, 663 (22) 
general measures, 663 (22) 
Arsenic (cont.): 
treatment of (cont.): 
of cyanosis, circulatory collapse and 
shock, 663 (22) 
of neuritis, 663 (24) 
of skin disturbances, 663 (24) 
relief of pain and diarrhea, 663 (22) 
sodium thiosulphate in, 663 (23) 
Arsine, 623, 663 (24) 
treatment of, 663 (24) 
Barium, 610 
Benzene, 648, 663 (37) 
acute poisoning with, 649, 663 (37) 
anemia from, 650 
treatment of, 663 (38) 
blood changes from, 649, 650, 652 
bone marrow in, 652, 653 
chlor compounds of, 662 
chronic poisoning from, 650 
classes of cases of, 651 
clinical picture of, 684 
derivatives of, 657 
diagnosis of, 650, 652 
leucopenia in, 649 
newer knowledge of, 652 
platelets in, 649, 652 
polycythemia in, 650 
red blood cells in, 650, 652 
skin hemorrhages from, 648 
treatment of, 663 (37) 
urine test of, 651, 652 
Benzene, chlor compounds of, 662 
Benzene derivatives, 657 
Benzene series of solvents: see Aromatic 
and benzene series of solvents, 648 
Benzine, 663 (10-12) 
Beryllium, 657 
Betanaphthylamine, 660 
Bibliography, 663 (44) 
Body resistance in relation to, 602 
Brass chills, 615 
Bromine compounds of the hydrocarbons, 
647 
Butadiene, 663 (5), 663 (41) 
treatment of, 663 (41) 
Cachexia fluorica, 608 
Cadmium, 615, 663 (24) 
prophylaxis of, 663 (25) 
treatment of, 663 (24) 
Carbitol, 632 INDEX 
3 
Carbon arcs, gas from, 663 (17) 
prophylaxis of, 663 (17) 
Carbon disulphide, 663 (1), 663 (40) 
gastric symptoms from, 663 (5) 
history of, 663 (2) 
nervous system changes from, 663 (2) 
prophylaxis of, 663 (40) 
treatment of, 663 (40) 
Carbon monoxide, 663 (10), 663 (43-6) 
action of, on heart, 663 (10-2) 
acute poisoning with, 663 (10-2) 
asphyxia from, 663 (10-2) 
chronic poisoning with, 663 (10-5) 
course of, 663 (10-2) 
glycosuria from, 663 (10-4) 
quantity required for symptoms from, 
663 (10-1) 
sequelae to acute poisoning with, 663 
(10-3) 
treatment of, 663 (43-6) 
oxygen and CO2 inhalations, 663 (43- 
7), 663 (43-9) 
Carbon tetrachloride, 636, 663 (29) 
chronic poisoning with, 638 
nervous disturbances from, 638 
prophylaxis of, 663 (30) 
symptoms of, 637 
treatment of, 663 (29) 
calcium, blood increase, 663 (29) 
dextrose solution in, 663 (29) 
digitalis in, 663 (30) 
diuretics in, 663 (30) 
insulin in, 663 (30) 
other medications, 663 (30) 
protein in diet in, 663 (29) 
visual disturbances from, 638 
Cellosolves, 631, 632 
Chlor compounds of benzene, 662 
Chlorinated hydrocarbons, 635 
Chlorinated naphthalenes, 645, 663 (34) 
jaundice from, 646, 647 
prophylaxis of, 663 (34) 
treatment of, 663 (35) 
Chlorine, 605, 663 (13) 
treatment of, 663 (13) 
Chlorotoluidine, 660 
Chromates, 609 
Chromic acid, 609 
Chromium, 609, 663 (21) 
prophylaxis of, 663 (21) 
Chromium (cont.): 
treatment of, 663 (21) 
Coal tar benzene: see Benzene, 648, 663 
(37) 
Copper, 620 
Cryolite, 608 
Cyanides, 627, 663 (27) 
treatment of, 663 (27) 
circulatory stimulants in, 663 (28) 
diet in, 663 (29) 
methylene blue in, 663 (27) 
respiratory stimulants in, 663 (28) 
sodium nitrite in, 663 (28) 
sodium thiosulphate in, 663 (28) 
Diagnosis and pathology, 600-663 (IO) 
Diethylene dioxide, 633 
Differences from general toxicology, 600 
Dimethylbenzene, 654 
Dinitrobenzene, 659 
Dinitrocresol, 660 
Dinitrophenol, 659 
Dioxan, 631, 633 
Diphenyls, 662, 663 (34) 
Electric ophthalmia, 663 (16) 
Entry paths of industrial poisons, 600 
Ether, 633 
Ethylene chlorhydrin, 645 
Ethylene dichloride, 643, 663 (34) 
treatment of, 663 (34) 
Felt industry and mercury poisoning, 612 
Fluorides, 608 
Fluorine, 608, 663 (14) 
treatment of, 663 (14) 
Fluorosis, 609 
Formaldehyde, 631 
Furfural, 633 
Gas gangrene from magnesium, 618, 663 
(22) 
Glycols, 631, 663 (35) 
treatment of, 663 (35) 
Hatter’s trade and mercurialism, 612 
Hexachlorethane, 644 
Hexamethylenetetramine, 634 
Hydrochloric acid, 605 
Hydrogen arsenide, 623 
treatment of, 624 
Hydrogen fluoride, 608 
Hydrogen sulphide, 663 (10-7), 663 (43—7) 
doses, fatal, of, 663 (10-8) 
oil refineries and, 663 (10-8) 4 
INDEX 
Hydrogen sulphide (cont.): 
prevention of, 663 (43-7) 
sources of, 663 (10-7) 
treatment of, 663 (43-7) 
of respiratory failure from, 663 (43-7) 
Individual susceptibility to industrial poi- 
sons, 602 
Industrial solvents, 629, 648 
aliphatic, 629 
aromatic, 648 
benzene, 648 
petroleum, 629 
Ingestion of industrial poisons, 601 
Inhalation of industrial poisons, 600 
Inorganic acids, 604 
Introduction to pathology and diagnosis, 
600 
Introduction to treatment and prevention, 
663 (n) 
Ketones, 630 
Lead, 610.(1), 663 (43) 
absorption of, 663 (43) 
arthralgia from, 610 (6) 
blood cell changes from, 610 (7) 
blood pressure changes from, 610 (11) 
colic from, 610 (5), 610 (12) 
compounds of, in industry, 610 (1) 
diagnosis of poisoning from, 610 (7) 
encephalopathia saturnina, 610 (5), 663 
(43-6) 
exposures to, 610 (3) 
hematoporphyrin from, 610 (8) 
in blood, 610 (8) 
in feces, 610 (8) 
in urine, 610 (8) 
kidneys and, 610 (10) 
lead line, 610 (8) 
legal responsibility, 610 (7) 
nephritis and, 610 (10) 
oxyacetylene torch and, 610 (2) 
painter’s colic, 610 (3) 
palsy from, 610 (6), 663 (43-6) 
peptic ulcer from, 610 (11) 
pregnancy and, 610 (6) 
prophylaxis of, 663 (43-10) 
signs of, 610 (5) 
soldering and, 610 (2) 
storage in body of, 663 (43-1) 
symptoms from, 610 (5), 610 (9) 
tetraethyl, 610 (2), 610 (3), 610 (9) 
Lead (cont.): 
toxicity, relative, of compounds of, 610 (i) 
toxicity, variations in, of compounds of, 
610 (i) 
treatment of, 663 (43-2) 
advisability of deleading, 663 (43-5) 
benefits vs. drawbacks of, 663 (43- 
6). 
ascorbic acid in, 663 (43-6) 
calcium diet with high phosphorus and 
vitamins, 663 (43-4) 
deleading by high calcium diet, 663 
.(43-3) 
disadvantages of, 663 (43-4) 
of encephalopathy, 663 (43-6) 
of palsy, 663 (43-6) 
Magnesium, 618, 663 (22) 
gas gangrene from, 618 
treatment of, 663 (22) 
treatment of, 663 (22) 
Manganese, 613, 663 (20) 
diagnosis of, 613 
prophylaxis of, 663 (20) 
symptoms of, 613 
treatment of, 663 (20) 
Maximum allowable concentrations for, 608 
Mercury, 611, 663 (17) 
diagnostic sign in eye, 613 
muscular tremors from, 611 
psychosis from, 611 
stomatitis from, 611 
symptoms of, 611 
treatment of, 663 (17) 
of acute, 663 (17) 
of chronic, 663 (19) 
of gastrointestinal involvement from, 
663 (18) 
of nervous disorders from, 663 (19) 
of stomatitis from, 663 (19) 
Mercury fulminate, 613 
Metal fume fever, 614, 663 (24) 
magnesium and, 615 
treatment of, 663 (24) 
zinc and, 614 
Methyl alcohol, 629 
Methyl benzene, 654 
Methyl bromide, 647 
Methyl cellosolve, 632 
Methyl chloride, 644, 663 (33) 
treatment of, 633 (33) INDEX 
5 
Metol, 634 
Monochlormethane, 644 
Nickel, 621 
Nitric acid, 606 
Nitrobenzenes, 657, 663 (40) 
treatment of, 663 (40) 
Nitrochlor, 662 
Nitrogen oxides, 606, 663 (15) 
treatment of, 663 (15) 
Nitroglycerine, 634 
Nitrotoluenes, 657 
Nitrous fumes, treatment of, 663 (15) 
Oxalic acid, 634 
Oxides of nitrogen, 606 
Oxygen therapy in, 663 (43-9) 
Paraphenylenediamine, 660 
Paris green, 622 
Pathology and diagnosis, 600-663 (IO) 
Pentachlorethane, 644 
Petroleum distillates, 663 (10-9), 663 (43-8) 
acute poisoning from, 663 (10-10) 
benzine poisoning from, 663 (10-13) 
carcinogenic substances in, 663 (10-14) 
concentrations allowable, 663 (10-10) 
treatment of, 663 (43-8) 
* acute, 663 (43-8) 
chronic, 663 (43-9) 
Petroleum solvents, 629 
Phenol, treatment of, 663 (39) 
Phosgene, 606, 663 (32) 
treatment of, 663 (32) 
Phosphine, 627 
Phosphoretted hydrogen, 627 
Phosphorus, 625 
Phossy jaw, 626 
Prevention and treatment, 663 (1 i)-663 (43) 
Pyrene fire extinguisher, 637 
Race in relation to susceptibility in, 603 
Radioactive substances, 663 (7), 663 (41) 
anemia from, 663 (9) 
bone lesions from, 663 (9) 
osteogenic sarcoma from, 663 (9) 
Radium, 663 (7), 663 (41) 
prophylaxis of, 663 (41) 
treatment of, 663 (41) 
Rubber, synthetic, 663 (5) 
Selenium, 625, 663 (26) 
prophylaxis of, 663 (26) 
treatment of, 663 (26) 
Sex in relation to susceptibility, 604 
Silver, 621 
Skin absorption in relation to industrial 
toxicology, 600 
Solvents, industrial, 629, 648 
aliphatic, 629 
aromatic, 648 
benzene, 648 
petroleum, 629 
Sulphur dioxide, 605, 663 (12) 
treatment of, 663 (12) 
of eye from, 663 (12) 
of respiratory disturbances from, 663 
(12) 
Sulphuric acid, 604 
Synthetic rubber, 663 (5) 
Tellurium, 625, 663 (26) 
prophylaxis of, 663 (26) 
treatment of, 663 (26) 
Tetrachlorethylene, 642, 663 (32) 
acute atrophy of liver from, 643 
leucocytes, changes in, from, 644 
treatment of, 663 (32) 
Tetrachlormethane, 636 
Tetryl, 662 
TNT, 661 
Tobacco, 663 (6) 
Toluene (toluol), 654 
blood changes from, 654 
symptoms of, 656 
Treatment and prevention, 663 (ii)-663 
(43) 
foreword to, 663 (n) 
Trichlorethylene, 639, 663 (31) 
addiction to, 642 
narcotic action of, 639 
nervous system symptoms from, 640 
optic nerve injury from, 641 
prophylaxis, 663 (31) 
treatment of, 633 (31) 
diet in, 633 (32) 
of acutely ill, 633 (31) 
of dermatitis from, 633 (31) 
of gray stage from, 633 (32) 
of phosgene formed from, 663 (32) 
of shock from, 663 (32) 
trigeminal nerve, effect of, on, 641 
Trinitrotoluene, 661 
Vanadium, 619, 663 (27) 
prophylaxis of, 663 (27) 
treatment of, 663 (27) 
toxicology, 600 6 
Vinyl cyanide, 627 
Welding, 634, 663 (16) 
acetylene and, 634 
electric ophthalmia from, 663 (16) 
prophylaxis of, 663 (16) 
treatment of, 663 (16) 
INDEX 
Xylene (xylol), 654 
Zinc, 619, 663 (25) 
metal fume fever from, 615, 619 
prophylaxis of, 663 (25) 
Zinc chloride burns, treatment of, 663 
(26)