EXPERIMENTS RELATIVE TO THE FORM IN WHICH AR- 
SENIOUS ACID MAY BE BEST APPLIED FOR DEVI- 
TALIZING THE PULPS OF TEETH 
W. D. MILLER, M.D., D.D.S., Berlin 
[Reprinted from the Dental Cosmos for September, 1894.] 
The question of the action of arsenious acid upon the human 
economy has long been a subject of investigation among pharma- 
cologists and physicians. Nevertheless, the way in which the com- 
plex of symptoms characteristic of arsenic-poisoning is brought 
about remains to the present a subject of dispute. 
According to the theory of Liebig,* arsenic acts upon living tissue 
in a manner similar to sublimate, the tissue being converted into an 
albuminate of arsenic ; at the same time, of necessity, losing its vital- 
ity. This theory received little credence because it does not accord 
with the most common observations regarding the local action of 
arsenic, and because all attempts to produce an albuminate of arsenic 
have thus far failed. 
The oscillation theory of Binz, j which has attracted much atten- 
tion, notwithstanding its ingeniousness seems to meet with a great 
deal of adverse criticism. 
By a series of experiments on animals, Binz arrived at the follow- 
ing results : 
1. In the living organism acid is converted into arsenic 
acid, and arsenic acid into arsenics acid. 
2. These two transformations are brought about in a short time by 
protoplasmatic tissue, within as well as without the animal body. 
3. Those tissues which during life are most affected by the action 
of arsenic are the ones to most readily give up their oxygen to 
arsenious acid outside of the organism. 
From these results Binz came to the conclusion that the conversion 
and retro-conversion of these two acids into each other bring about 
a violent oscillation of the atoms of oxygen within the protoplasm, 
and this is the cause of the poisonous action of arsenic. It acts only 
as the carrier of oxygen. 
Binz compares the action of arsenic to the destruction of organic 
matter by iron in the presence of air and moisture. Ferric oxid gives 
up an atom of oxygen to the organic matter, becoming thereby re- 
duced to ferrous oxid ; but this compound cannot exist in the presence 
of air and moisture, ferric oxid being formed almost immediately, 
which then again gives up its oxygen to the organic matter. This 
process, continued indefinitely, brings about an oxidation or combus- 
tion of the matter. In this way iron nails in wood become quite 
* Die Chemie in ihrer An LjJ 1843. 
| Pharmacologic, 2. Aufi., jrSgi, pft 41%. *' 2 
loose in time, and iron-stains eat holes in linen. Husemann,* who 
is the most outspoken opponent of Binz, points out that in accordance 
with the oscillation theory arsenzV acid should exert the same action 
or as strong an action upon living tissue as does arsenics acid. 
This, however, does not agree with the results of experiments or 
clinical observations. 
The discordance of the views regarding the local action of arsenic 
is still more pronounced. Some designate it as a violent escharotic, 
others assert that it has no escharotic action whatever. Some claim 
that it acts only upon diseased tissue. How this opinion was ever 
arrived at is to me incomprehensible. Some find it to act upon the 
central nervous system, others upon the peripheral nerves. 
In regard to the patho-histological changes brought about by local 
applications of arsenic, I know of no investigations more worthy of 
consideration than those of Arkovy :f 
“i. As203 brought into contact with the tooth-pulp acts in the 
following way ; A certain degree of inflammatory hypersemia, total 
or partial, depending upon the quantity of the agent applied, sets 
in ; the blood-vessels become expanded, and here have a tendency 
to thrombosis. This latter effect may also be in connection with 
embolism of the capillaries, when the agent is quickly taken up into 
the blood-vessels. 
“2. As203 produces no coagulation of tissue whatever. 
“3. It has a specific influence upon the blood-corpuscles, combin- 
ing with the haemoglobin to form a compound of arsen-haemoglobin, 
and of this chemical process there seems to be evidence in the pro- 
fuse yellowish tinge of the whole pulp-tissue, and in the discoloration 
of blood in several of the blood-vessels. 
“4. In nearly every case it is taken up in substantia (in form of 
molecules) into the blood-ways ; when there it produces, besides the 
above-mentioned changes, granular detritus of the contents and 
anaemic collapse, shrinkage,—the latter effect being brought about 
nearly exclusively in cases where greater doses were used. 
“5. The bulk of the pulp-tissue—viz, connective-tissue fibers and 
odontoblasts—undergoes no change whatever ; not so the connective- 
tissue cells, which increase three to four times their normal size. 
“ 6. The special action of arsenic trioxid upon the nerve-elements 
consists in the following : The neurilemma is only so far influenced 
that its nuclei are somewhat increased ; a more essential change takes 
place in the axial part, where, after the application of more than one 
mgrm., granular detritus of myelin sets in, and the axis-cylinder 
commences here and there to disappear. As a very surprising altera- 
tion may be regarded the notchy tumefaction of the axis-cylinder, 
described heretofore almost only in cases of central lesions. 
‘ ‘ 7. All these alterations occur in and among normal-looking tissue. 
“8. The action of arsenic trioxid is macroscopically exhibited by 
a brownish-red tinging of the whole or of certain parts of the pulp- 
body, as well as of the neighboring dentine and cementum, this 
latter in cases treated with greater doses,—viz, two to five mgrms. 
This alteration is most expressed .at the top of the crown-pulp and 
at the apical one-fourth to one-third part. This circumstance may 
* Deutsche vied. Wochenschrift, 1882, Nos. 48-50. 
t Transactions Internat. Med. Congress, Dental Section, London, 1881. be considered as an external evidence of the devitalization being 
completely attained to.” 
In view of the results obtained by Arkovy, I thought that I might 
be spared the labor of extending my investigations to the histological 
changes which are produced by local applications of arsenious acid, 
devoting my time chiefly to the clinical aspect of the question, and 
in particular to the question, In what form should local applications 
to the dental pulp be made ? 
In applying arsenic to the pulps of dogs’ teeth, it is impossible to 
bring about the same conditions in every case ; either the pulp is 
more exposed in one case than in the other, as it is more wounded, 
or the bleeding may interfere more in one case than in the other. 
Again, the quantity of arsenic applied cannot be absolutely the same 
in all cases, etc. 
To eliminate these and various other sources of error, it is necessary 
to make a large number of experiments, which, as every one knows 
who has experimented upon dogs, is a matter of great difficulty. 
Experiments upon pulps have the further inconvenience that it is 
impossible to study with the naked eye changes which are going on 
in the pulp intra vitam, and which may be of great aid in determin- 
ing the nature of the process. Chiefly, however, for the reason that 
my experiments dealt with the comparative action of various forms 
of the paste, I found it desirable to choose a subject for experimenting 
upon which was more easily accessible than the pulp of dogs’ teeth. 
A few trials only were made on frogs and rabbits, as these animals 
soon proved to be ill adapted to the purpose. 
The greatest number of experiments was made on the tails of white 
mice. This organ presents in so far a similarity to the pulp, as it is 
comparatively long and narrow, and traversed in the direction of its 
length by central blood-vessels and nerves. 
To make the similarity greater, I passed, in some cases, a glass ring 
over the tail, fitting closely at the root, to take the place of the con- 
striction at the apical foramen. 
Again, in a number of cases I inclosed the tail, after applying the 
arsenic, completely in a plaster cast. This was accomplished by 
filling a proper-sized glass tube with a thin mixture of plaster of Paris 
and drawing it over the tail, or rather drawing the tail into it by 
means of a thread tied to the tip of the tail. Finally, for this opera- 
tion, tubes were used which were broken through on one side about 
an inch from the end. As soon as the cast had hardened, the plaster 
was removed through this opening sufficiently to expose the tail, at a 
circumscript point. The slit was then made, arsenic paste applied, 
protected by gold foil, and the opening closed with plaster of Paris. 
To whatever part the arsenic was applied, the most prominent 
symptom manifested was the enormous swelling and oedema (except 
where the tail was inclosed in a cast). Applied in a skin pocket 
above the root of the tail, the whole rump and the hind legs became 
intensely swollen and appeared yellowish, and semi-transparent on 
holding the mouse toward the light. 
On incision, a large quantity of yellowish serum escaped. Com- 
plete anesthesia and paralysis of the hind legs usually resulted, the 
mice sometimes gnawing them off. Death frequently followed the 
application, unless very small quantities were used. 4 
When arsenic was applied to the ear, after slightly scraping or 
cutting it, the ear appeared in twenty-four hours swollen, red, and 
succulent; later a portion of the ear, or sometiilies the whole of the 
external ear, was thrown off. 
In working upon the tail, a longitudinal slit was made through the 
skin about one-quarter of an inch long, being careful to avoid the 
blood-vessels, which in white mice are distinctly visible. The skin- 
flaps were slightly raised and the paste inserted. In twenty-four 
hours marked swelling extending about one-half an inch in each 
direction from the point of application, sometimes over the whole 
tail. In the vicinity of the wound the tissue appeared reddish to 
bluish-red ; farther removed there was sometimes no reddening what- 
ever, the tail appearing swollen, waxy, and oedematous. In forty- 
eight hours the whole tail was intensely swollen, bluish-red ; in many 
Showing the action of arsenious acid on mouse-tails, a, normal tail; b, tail thiity-six houi s, 
c, foity-two hours, after application of arsenic paste ; d, tail with glass ring. 
cases the skin was found cracked open and drops of serum exuding. 
A free flow of serum followed an incision. In seventy-two hours tail 
blue and wilted (dead). Complete anesthesia of the greater part of 
the tail was found to be present in about forty-eight hours. 
The action of the arsenic appeared somewhat accelerated in those 
cases where a closely-fitting glass ring was put on the tail near the 
root, and the arsenic applied one-quarter to one-half an inch below 
the ring. These rings were set on the root of the tail with gum 
arabic or plaster of Paris, and allowed to remain for twenty-four 
hours before the arsenic was applied. This precaution was taken in 
order to make sure that the ring was not tight enough to produce 
any disturbance in the circulation. 
In more than forty cases, there was not one in which the action of 
the arsenic extended beyond the ring. 
One of the most pronounced symptoms produced by the arsenic is 
the oedema. This fact suggests the thought that the death of the pulp 
might be due in part to a strangulation brought about by the pres- 
sure within the rigid walls of the pulp-chamber. If this were the case, 5 
we should expect tails in a plaster cast to be devitalized more quickly 
than when they were free to expand. The experiments did not, 
however, furnish much evidence in favor of this view. The differ- 
ence was so slight that I was obliged to repeat the experiments fifteen 
times before I could come to a conclusion, which is, that the action 
of the arsenic is not appreciably influenced by enveloping the organ 
in a rigid cast. In some cases the action appeared to be more diffuse, 
in some loss of sensibility appeared to occur sooner, but no constant 
pronounced difference could be detected. 
From these results we cannot, however, with certainty, conclude 
that the pressure within the pulp-chamber has no part in bringing 
about death of the pulp, since its effect may be compensated for by 
a diminished absorption of the arsenic, resulting from the increase of 
pressure within the tissue. That the death of the pulp is not due 
solely to a strangulation of the vessels at the apical foramen will be 
evident from the fact that arsenic acts locally upon tissue that is per- 
fectly free to expand. The action of arsenic is of a progressive 
nature, beginning at the point of application and extending gradually 
in each direction. The peripheral portion of the tail, of course, dies 
in toto as soon as a complete stagnation is brought about at the point 
of application of the paste. 
The view formerly entertained by many, that arsenic acts only upon 
diseased tissue, is untenable. 
Arsenic is still described by many as a powerful escharotic, 
although nearly all who have experimented with it have pointed out 
that it has no action of the nature of the well-known escharotics, 
such as carbolic acid, chlorid of zinc, etc. 
The local application produces no immediate visible effect whatever. 
It is well known that different tooth-pulps show, very great differences 
in their susceptibility to the action of arsenic. The age of the patient, 
the size of the pulp, the freeness of the exposure, and particularly 
the condition of the pulp as to calcifications, have a marked effect 
upon the rapidity of absorption of the paste, so that, while in many 
cases death of the pulp occurs within twenty-four hours, in others 
again repeated applications may be necessary to accomplish the pur- 
pose. The rapidity of action naturally depends to a certain extent 
upon the amount of arsenic applied, and upon the action of the sub- 
stances with which it is incorporated. 
The form in which arsenic was for many years solely applied to the 
pulp is in connection with creasote or carbolic acid and morphia ; 
in later years we hear much of the essential oils and lanolin as base, 
with addition of iodoform, cocain, etc., to prevent the pain often 
attendant upon the devitalizing process. 
I have experimented upon mice, and to some extent upon dogs, 
with the following combinations ; 
1. Arsenious acid ; chlorid of zinc. 
2. Arsenious acid ; carbolic acid. 
3. Arsenious acid ; oil of cloves. 
4. Arsenious acid ; lanolin. 
5. Arsenious acid ; thymol ; oil of cloves. 
6. Arsenious acid 1 ; thymol 2 ; oil of cloves. 
7. Arsenious acid ; glycerin. 
8. Arsenious acid ; 5 per cent, aqueous solution of common salt. 
9. ArsemV acid. 6 
In each case a sufficient quantity of the liquid was added to form a 
paste. No. 9, being deliquescent, soon formed a paste of itself when 
exposed to the air. 
No. 1 applied to the ear produced shriveling at the point of appli- 
cation, caused by the chlorid of zinc. This prevented the absorption 
of the arsenic, and consequently the characteristic arsenic effect did 
not appear at all. 
On the tail the escharotic action of the chlorid of zinc was very 
pronounced, in half an hour a white patch having formed one-fourth 
to one-half inch long and extending half-way around the tail. 
At the same time a marked contraction or constriction of the tail 
was produced. This constriction apparently retarded the absorption 
of the arsenious acid, the rapidity of action, on the whole, being less 
than where the mixture No. 2 or 3 was used. 
Application of No. 2 to the ear produced more or less redness and 
swelling, with death of a limited portion of the ear. 
No. 3 produced a much more powerful action than either 1 or 2, 
when the application was made to the ear or to the tip of the tail. 
When applied under a skin-flap near the root of the tail, it did not 
act so very much more promptly than No. 2, though, on an average, 
there was still a difference in its favor. 
No. 4 produced but very slight action in all cases ; usually it was 
little more than zero. 
In the Dental Cosmos for 1893, page 805, I called attention to 
the fact that the pain which is so frequently produced by applications 
of sublimate to the teeth may be in a great degree or entirely avoided 
by the addition of thymol. This led to the thought that thymol 
might be a valuable ingredient of arsenic paste. 
Experiments were accordingly made with the mixture No. 5. As 
was anticipated, the action was much milder than that produced by 
No. 3, since a given quantity of the paste contains only about half 
to two-thirds as much arsenic as an equal quantity of No. 3. It was, 
however, equal to that produced by an application of a mixture of 
morphia and arsenious acid in oil of cloves, and we have reasons 
for thinking that the local anesthetic action of thymol exceeds that 
of morphia. Many, indeed, deny that morphia has any local anes- 
thetic action at all. Thymol has, further, the decided advantage of 
a considerable antiseptic action. At the Dental Institute I have been 
making use of a paste having the following composition : 
R—Thymoli, 
Acidi arsenicosi, aa x ; 
01. caryoph., q.s. ut ft. pasta. 
We have no reason thus far to be other than satisfied with the 
results. One disadvantage of this mixture lies in the fact that part 
of the thymol separates from the arsenic in crystalline form, render- 
ing it necessary to stir the paste from time to time. This difficulty 
might no doubt be overcome by a slight alteration in the composition 
of the mixture, possibly by the addition of glycerin. 
The effect produced by applications of No, 6 was decidedly less 
than that by No. 5. Further dilution of the paste was not attempted, 
although we are perfectly safe in concluding that by increasing the 
proportion of thymol we may reduce the strength of the paste to any 
desired extent. 7 
A paste made of arsenious acid with water acted quite as promptly 
as when oil of cloves was used. Nos. 7 and 8 were tested each only 
four times. They produced the impression of acting at least as 
promptly, if not still more rapidly, than the paste with oil of cloves. 
The action of arsenic acid was very marked. A small quantity of 
this taken upon a glass slide deliquesces immediately, so as to form a 
thin paste. An amount of this about equal in size to the head of a 
pin, applied to a slit in the tail of a mouse, caused death in four 
cases out of five inside of four hours ; paralysis of the hind legs, 
diarrhea, and, in one case, convulsions, being the chief symptoms. 
Arsenic acid also produced a local escharotic action, similar to that 
of carbolic acid, though in a much less degree. 
In the fifth case, the mouse showed the symptoms just stated to 
such an extent that it was expected to die at any moment; it 
recovered, however, and on the following day appeared perfectly 
well; the local action was scarcely visible. 
The results recorded above point to the following practical con- 
clusions : 
1. The rapidity and intensity of the action of arsenious acid depends, 
under certain circumstances, to a very considerable degree upon the 
substance or substances with which it is incorporated. 
2. Where there is but a small point of exposure, and in particular 
where extensive calcification has taken place in the pulp, escharotics 
should be avoided, since the contraction of the tissue retards the ab- 
sorption of the arsenic. This retardation is but slight where there is 
a broad surface of exposure. 
In stubborn cases where applications of the ordinary paste fail to 
effect the devitalization, a paste consisting of arsenious acid in oil of 
cloves, glycerin, or salt solution should be employed, undiluted by 
any third constituent.. 
3. Thymol is worthy of a trial as a substitute for morphia, on 
account of its anesthetic and antiseptic properties. 
4. For devitalizing pulps of milk-teeth or remains of pulp-tissue in 
root-canals, arsenious acid, if employed at all, should be diluted by 
two to three parts of some other constituent (thymol, oxid of zinc, 
morphia, iodoform). 
In fact, in all cases where, for any reason, a milder action of the 
arsenic is desired, it may naturally be employed in this diluted form. 
In these cases Arkovy recommended the use of pepsin for devitaliz- 
ing the pulp. 
The question naturally arises whether results deduced from experi- 
ments on mice apply equally well to the pulps of human teeth. It is 
my impression that such is the case. Nevertheless, it would un- 
doubtedly be well to supplement the above experiments by experi- 
ments on the pulps of teeth, although it will always be found very 
difficult to secure the variety of conditions in dogs’ pulps which we 
meet with in the pulps of human teeth. Experiments on nine teeth 
(three dogs) gave results which fairly correspond with those reported 
above. 
I give the results of my experiments to the profession at this time 
because I am about to interrupt my work for three months, and do 
not care to delay so long with the publication.