+- __T,wr.v---.*-(p.

++ + --

ON THE TOXICITY OF DEXTRO-, LAEVO- AND INACTIVE

CAMPHOR

w. E. GROVE, M.D.

From the Pharmacological Laboratory of the University of Wisconsin

Received for publication, November 17, 1909

Ever since th discovery of stereo-isomerism in carbon compounds

a great deal of interest has been manifested in the differences in the
physiological and pharmacological action of optical isomers. Although
from the pharnacological and toxicological points of view, the great
mass of the work has been done in the last few years yet Schmiede-
berg,’ as early as 1901, made the far reaching statement that up to
that time all pharmacological knowledge indicated that the degree
of pharmacological activity of a substance is dependent upon its
stercochemical configuration, the kind of pharmacological action, on
the other hand, being more dependent on its chemical constitution.
In 1904 Mayor’ examined the toxicity of laevo- and dextro- nico-
tine for Pictet and Rotschy who were working on the chemistry of
these substances. He found that for guinea pigs weighing approxi-
mately 300 grams the toxicity of laevo-nicotine was just double that
of dextro-nicotine. Moreover, the subcutaneous injection of dextro-
nicotine seemed to be quite painless while laevo-ni#{233}otine, similarly
introduced, produced excitement and a cry of pain. According to
Mayor the kind of reaction produced by these two antipodes is differ-
ent, the dextro-nicotine producing trembling and weakness but never
any real convulsions, whereas the laevo-nicotine always produced
typical convulsions.
Cushney,3 working with laevo-hyoscyamine and with pure atropine,
which is a mixture of equal parts of laevo- and dextro-hyoscyamine,

‘0. Schmeideberg: Berichte d. deutsch. chem. Gesellsch., 34,2550, 1901.

2 Pictet and Rotschy: Berichte d. deutsch. chem. Gesellsch., 37, 1225, 1904.
‘Cushney: Jour. Physiol., 30, 176, 1904.
446 w. E. GROVE

came to the conclusion that pure atropine and hyoscyamine act in the
same way and with equal potency on the central nervous system of
mammals, and on the heart and motor nerve terminations of the frog.
Atropine stimulates more powerfully than hyoscyamine the reflexes
of the spinal cord in the frog. Hyoscyamine has almost twice as
powerful an action on the nerve endings in the salivary glands, heart
and pupil. The fact that atropine acts as a much more powerful
stimulant than laevo-hyoscyamine on the spinal cord of the frog would
indicate that the dextro-hyoscyamine has a specific strychnine like
action not I)OsseSSed by the laevo-hyoscyamine. Experiments with
pure dextro-hyoscyamine prove that this inference is in accord with the
facts. Cushney concludes that some organs have the property of
differentiating between optical isomers, while other organs are devoid
of this power. Cushney and Peebles4 showed also that the two hyos-
cines bear the same relation to each other as was found in the case
of the two hyoscya mines with regard to their action on the salivary
secretion and on the inhibitory fibers in the heart, laevo-hyoscine
being twice as powerful as dextro-hyoscine. The two alkaloids have
similar general effects upon frogs differing in this respect from atro-
pine and hyoscyaniine. The toxicity of the two niodifications of the
alkaloid for mammals appears to be about the same.
Similar differences in the action of optical isomers is also exhibited
by the two adrenalins. Cushney,5 using the natural laevo-adrenalin
obtained from the gland and the inactive synthetic adrenalin prepared
by Meister, Lucius and Brilning, showed that the racemic adrenalin
was only one-half as powerful in raising the blood pressure of dogs as
the natural laevo-adrenalin. Abderhalben and Miller,0 working with
laevo- and dextro-adrenalin prepared by Fl#{228}cher7 from synthetic
adrenalin, and also with the natural laevo-adrenalin obtained from the
gland, were able to demonstrate that laevo-adrenalin, both natural
and artificial, was fifteen times as powerful as the dextro-forni in
raising the blood pressure of dogs and rabbits. It was further shown

(‘ushney and Peebles: Jour. Physiol.. 32, 501, 1906.

‘ Cushncy: Jour. Physiol., 37, 130, 1908.
I Abderhalben ii. MUller: Ztschr. f. physiol. chem., 58, 185, 1909.
FlUcher: Ztschr. f. physiol. cheni., 58, 189, 1909.
 r:’-’’ -,P’ - - .-
++, + 4 - ,-4 .Nv--- +- -+ .

:1

TOXICITY OF CAMPHORS 447

by Abderhalben and Thies8 that dextro-adrenalin does not call forth

glycosuria in the doses that are quite sufficient with laevo-adrenalin,
nor does dextro-adrenalin call forth more than a very slight dilatation
of the pupil of the frog’s eye. Abderhalben and Slavu9 showed that to
mice weighing from 10 to 12 grams 0.1 mg. of laevo-adrenalin was
fatal after a preliminary fall of body temperature of from 10#{176}
to 15#{176}
C.
Similar doses of dextro-adrenalin produced no other effect than a
slight drop in body temperature. Dextro-adrenalin was fatal only in
doses of 0.5 gram. The laevo-form is therefore about 5000 times as
toxic as the dextro-modification. Moreover, they brought out the
interesting fact that by first treating mice with dextro-adrenalin they
were able to increase considerably their resistance to laevo-adrenalin.
Langaard and Maass,’#{176} using preparations of dextro,- laevo- and
inactive camphor, were not able to demonstrate any action on the
normal frog’s heart in the case of either modification. After poisoning
the frog’s heart with chloral they were able to show that all modifica-
tions of camphor produced, after a short latent period, greater rhyth-
micity and an increased rate. They suspended their camphor in
physiological salt solution and then dropped it upon the heart. They
were able to obtain an excitation of the central nervous system with
all three modifications of camphor. In larger doses they were able
to produce convulsions with all three modifications. In this respect
they found that laevo-camphor was the most powerful, dextro-cam-
phor the least so and inactive camphor was intermediate between the
two. H#{228}m#{228}l#{228}inen”
agrees with Langaard and Maass in that none of
the modifications of camphor have any action on the intact heart of
the frog. However, when the frog’s heart is damaged by chioral
according to B#{246}hnie’s” method, he showed that dextro- and racemic
camphor have about the same degree of activity, being able to Iicrease
the rate of the heart beat for a considerable time and to start again a
heart which had been stopped by chloral. The stimulation called
forth by laevo-camphor was weaker, and of shorter duration, and

S Abdcrhalben u. Thies: Ztschr. f. physiol. chem., 59, 22, 1909.

‘Abderhalben u. Slavu: Ztschr. f. physiol. chem., 59, 129, 1909.
Langaard
‘#{176} u. Maas: Therap. Monatsh., 21, 573, 1907.
“H#{228}m#{228}lUinen: Skand. Arch. f. Physiol., 21, 64, 1908.
“,BOhme: Arch. f. Exp. Path. u. Pharmakol., 52, 347, 1905.
448 w. E. GROVE

after laevo-camphor had called forth its greatest activity the rate of
the heart could be still further increased by using dextro- or racemic-
camphor. The chloral stoppage of the heart could in no case be inter-
rupted by laevo-eamphor. The only statement that the writer has
been able to find as to the toxicity of camphor is that made by Soll-
mann’3 for the ordinary dextro-camphor. He states that 2 grams in
oil subcutaneously or by stomach will cause convulsions in a rabbit
and that 4 grams in oil by stomach convulsions in a dog and that 0.1
grain subcutaneously is fatal to frogs, death being preceded by
paralysis.
In my work dextro-, laevo- and racemic camphor were employed.
The dextro-camphor used was the ordinary camphor of commerce
which was purified by dissolving in absolute alcohol, filtering and
evaporating off the alcohol. This product melted sharply at 176#{176}
C.
The laevo- and racemic camphors, prepared by E. Schering, Berlin,
both melted very sharply at 176#{176}
C. Each of these three camphors
was dissolved in absolute alcohol, one part camphor to five parts alco-
hol by weight, and its specific rotation determined. The dextro-
camphor gave a specific rotation of + 43.83#{176}. The specific rotation
of the laevo-camphor was - 43.44#{176},while the synthetic camphor
was practically inactive [(a) d = - 0.63#{176}]. The room temperature dur-
ing these observations was 31.5#{176}C. Beckniann’4 found that both
dextro- and laevo-camphor melt at C. and
175#{176} when dissolved in
absolute alcohol in a one to five solution give a specific angle of rota-
tion of ± 44.22.#{176}
In niy own experiments both frogs and white rats were employed.
The camphor was in each case introduced under the skin of the back
in the form of a 10 per cent solution in pure olive oil. After a few
preliminary experiments to determine the approximate toxicity of
dextro-camphor 1 found it convenient to calculate my doses of camphor
in milligrams per gram of body weight of the animal.
In frogs I found that the minimal lethal dose of dextro-camphor was
between 3.1 ng. and 3.2 rug, per gram of body weight (table 1), while
that of laevo-camphor was 2.3 rug. per gram of body weight (table 2);
2.2 mg. per gram of body weight killed in 25 per cent of the cases. The
13 Sollmann: Text book of Pharmacology, p. 949, 1906.
‘ Beckmann: Annalen, 250, 352, 1889.
‘r- + ‘ N” + + . -

TOXICITY OF CAMPHORS 449

minimal lethal dose of the synthetic, dextro-laevo-, camphor, while

not as carefully determined as the other two, is about 2.7 rug. per gram
of body weight (table 3). Thus it is seen that dextro-camphor is only
three-fourths as toxic for frogs as the laevo-form while the inactive
camphor occupies a position midway between the other two.

TABLE 1

All these frogs were injected under the skin of the back with a 10 per cent solution of
dextro-camphor dissolved in pure olive oil.

0
0
H
‘4
OR
;.. ; N
DATE1909 0 ORE

May 20 61.0 2.0 3.2 45 Ifl. 4 h. 10 m. D 6 h. 40 m.

June 9 21.0 0.67 3.2 not noted 3h. 30m. R48h.
9 17.0 0.54 3.2 not noted 3h. 30m. D 8h.
9 19.5 0.62 3.2 not noted 3 h. 30 m. D 23 h. 30 m.
9 22.0O.74’ 3.2 not noted 3 h. Om. DiSh. 0 m.
May 22 24.0 0.75 3.1 not noted ‘not noted D 23 h. 15 m.
31 38.0 1.40 3.0 2h. Om. not noted R23h. 15 m.
June 5 24.0 0.72 3.0 2h. Oin. 3h. 45m. R48h.
5 22.0 0.66 3.0 2h. Om. 3h. 45m. R48h.
5 20.0 0.60 3.0 2h. Om. 3h. 45m. D24h.
7 22.0 0.66 3.0 2h. 15m. llh. 15m. R47h.
7 18.0 0.54 3.0 2h. 15m. llh. 15m. D28h.
7 19.0 0.57 3.0 4 h. 30 m. no loss R 47 h.
reflexes
2 35.0 1.00 2.9 lh. 25m. 6h. Om. R23h.
May 25 27.0 0.70 2.6 1 h. 30 m. no loss R 23 h.
reflexes

Due to variations in the conditions of the frogs used it is hardly possi-

ble to define more closely the limits of the minimal lethal dose. In
order to show the relative action of the three modifications of cam-
phor, I publish below the protocols of four of my experiments in which
a uniform dose of 2.6 rug. per gram of body weight of each of the three
modifications was employed. Each of the first three frogs respectively
received under the skin of the back 2.6 rug. per gram of body weight
450 W. E. GROVE

TABLE 2

All these frogs were injected under the skin of the back with a 10 per cent solution of
laevo-camphor in pure olive oil

S + ‘Z’O
0
O RD
H .3,
S
OR
DATE 1909 ;&.z s.
0 OHH

550

0
H

May 21 45.0 2.00 4.4 30 m. lh. 45m. D 5h. lOm.

22 30.0 0.93 3.1 lh. Om. lh. 20m. D lh.30m.
25 28.0 0.70 2.6 lb. 5m. lb. 45m. D 6h. Om.
June 4 24.0 0.55 2.3 lh. lOm. 5h. 30m. D 9h. 30m.
4 24.0 0.55 2.3 lb. lOm. 9h. 30m. R30h. Om.
4 31.0 + 0.71 2.3 lh. lOm. 5b. 30m. D23h. 15m.
4 30.0 0.70 2.3 lh. lOm. 9h. 30m. D25h. 30m.
2 39.0 + 0.85 2.2 lb. 30m. 6h. Om. Dllh. Om.
3 56.0 1.23 2.2 2h. Om. llh. Om. R24h. Om.
3 38.0 0.83 2.2 2h. Om. no loss R24h. Om.
reflexes
3 27.0 0.60 2.2 not noted not noted R24h. Om.
3 31.0 0.68 2.2 lb. 30m. not noted R24h. Om.
7 28.0 0.60 2.2 2h. 30m. not noted Dub. 30m.
7 20.0 0.44 2.2 2h. 30m. lh. 30m. R48h. Om.
7 20.0 0.44 2.2 2h. 30m. llb. 30m. R48h. Om.

TABLE 3

All these frogs were injected under the skin of the back with a 10 per cent solution of
dextro-laevo-camphor in pure olive oil

0
0
H

lIE
DATE-1909
HO

‘4-

May 25 32.0 0.83 2.6 lb. 25m. 3h. Om. R22 h. 0 rn

31 36.5 0.90 2.5 lb. 35m. 2h. 40m. R24 h. 0 rn.
lune 2 33.0 0.85 2.6 1 b. 10 m. 11 h. Om. D 13 b. 0 m.

NOTE-These experiments with dextro-laevo-camphor are not conclusive in them-

selves but were only made to see, in a rough way, whether the inactive-camphor
occupied a position midway between the dextro- and laevo-forms with regard to
toxicity.
 ++ . ‘I#{231}+ Y, 7 - ; + .‘ + - . . -? 2 + .

TOXICITY OF CAMPHORS 451

ofdextro- , laevo- and dextro-laevo-camphor. The caniphorwas given

in the form of a 10 per cent solution in olive oil. The fourth frog
received a corresponding amount of pure olive oil only.

Experiment 1

May 5, 10:16 a.m. Frog, weighing 27 grams, received dextro-camphor.

10:80 a.m. Respiration about 44 per minute. Frog is quite active. Jumps
about readily. Can regain ventral position when placed on back.
10:45 a.m. Respiration 40 per minute. Leaps voluntarily and regains ventral
position when placed on back, but not so actively as before.
11:00 a.m. Respiration 38 per minute. Frog does not show much desire for
spontaneous movements. Will
not leap on stimulation, but crawls about showing
a beginning paralysis of the hind legs. Cannot sit erect but lies flat with head on
floor most of the time. Will occasionally jump or crawl sluggishly. Regains ventral
position when placed on back.
11:19 a.m. Respiration 60 per minute. Frog lies flat with bead on ground.
Moves o,i stimulation but very sluggishly. Can still raise head from ground. Does
not regain ventral position when placed on back.
11:45 a.m. Heart 40 per minute and quite strong. Respiration very difficult
to make out. Foreleg reflex* present but not very active. Hind leg reflex absent.
Cannot regain ventral position when placed on back,
1:06 p.m. Heart 44 per minute and fairly strong. Convulsive tremor present
in the hind legs. All reflexes are increasing in activity. Muscular twitchings are
present in tbe muscles of the hind legs.
12:30 p.m. Reflexes present. Not exaggerated. Frog makes strong voluntary
kicking movements when placed on back.
3.’OO p.m. Respiration 24 per minute. Sits erect with head off floor. Jumps
voluntarily and on stimulation.
9:00 p.m. Respiration 13 per minute. Sits erect and regains ventral position
when placed on back, Almost normal.
9:30 a.m., May 26. Frog nqrmal.

* Nom-By the foreleg reflex is meant the convulsive adduction of the forelegs
of the frog when the under side of the jaw is stroked.

Experiment 2

10:17 a.m. Frog weighing 28 grams received laevo-camphor.

10:30 a.m. Respiration 45 per minute. Frog very sluggish. Regains ventral
position when placed on back, but with difficulty. Jumps sluggishly on extreme +

stimulation. Not nearly so active as the dextro-frog.

10:45 a.m. Respiration 33 per minute. Lies flat with head on floor. Makes a
few voluntary movements but very sluggishly. Reflexes are not increased.
11:05 a.m. Respiration 40 per minute. Heart 30 per minute. Can make a few
voluntary movements with the forelegs and can raise the forepart of the body trorn
the floor. Drags hind legs. Reflexes are present but very sluggish.

A
452 w. E. GROVE

I 1 :48 a.m . Respiration and heart beat are too feeble to be seen or counted . Frog
absolutely paralyzed. Hind leg reflexes gone. Foreleg reflex present but sluggish.
12:03 p.m. Heart 22 per minute. Reflexes gone.
1 :30 p.m . Heart 23 per minute. Reflexes gone.
.1:0() p.m. Heart 14 per minute. Reflexes gone.
4:15 p.m. Frog dead, 6 hours after injection.

Experiment 3

10:27 a.m. Frog weighing 32 grams received synthetic, dextro-laevo-campbor.

10:42 am. Respiration 50 per minute. Frog active. Leaps voluntarily.
11:08 am. Respiration 38 per minute. Leaps voluntarily. Cannot regain
ventral position when placed on back but is not absolutely- paralyzed. Reflexes
present and normal.
11:28 p.m. Respiration too irregular to count. Jumps slightly on stimulation.
Does not regain ventral position when placed on back. Reflexes present and normal.
11:51 p.m. Heart 38 per minute. Frog makes no voluntary movements.
12:10 p.m. Heart 38 per minute. Hind leg reflexes still present. Foreleg
reflex quite active. Muscular twitchings in muscles of the hind legs and shoulders.
If placed on the back and stimulated the frog makes kicking movements of the hind
legs but cannot regain ventral position.
1:30 p.m. Heart 28 beats per minute. All reflexes gone.

4:15 p.m. Heart 28 beats per minute. Very slight abdominal and foreleg
reflexes present. Hind leg reflexes gone.
9:00 pin. Reflexes reappearing and increasing. Frog makes a few voluntary
movements.

8:30 am. Frop apparently normal.

Experiment 4

10:28 am. Frog weighing 35 grams received 0.9 cc. of pure olive oil under the
skin of the back. This frog was observed for 2 hours during which time he
remained practically normal.
7:00 p.m. Frog quite normal.

These experiments show that the pharmacological action of laevo-,

dextro- and raceniic camphor in frogs does not differ in kind but
merely in degree. If a sufficient dose of either dextro-, laevo- or race-
mic camphor is given the movements of the frog gradually become
more sluggish as is shown by its disinclination to crawl or jump and
by its inability to regain the ventral position when placed on its back.
Coniplete paralysis ensues while the reflexes are still present. The
reflexes of the hind legs disappear first, then those of the forelegs. The
breathing after becoming more and more shallow, ceases entirely.
The heart becomes slower and weaker until death ensues. If the frog
 TOXICITY OF CAMPHORS 453

recovers from a severe intoxication the reflexes reappear before the

paralysis ceases.
Immediately after the injection of laevo-camphor the frog is more
lively and can jump farther than before the injection. This would
seem to indicate a primary stimulation of the central nervous system
by the laevo-form followed by a depression. Moreover, when these
frogs which have been treated with laevo-camphor recover, they are
found to be hypersensitive and their reflexes are greatly exaggerated.
In several of the frogs treated with laevo-camphor muscular twitch-
ings and subconvulsive tremors occurred. These were not observed
in the frogs treated with dextro-camphor.
It was noticed that the skin of a large number of the frogs which
were treated with any modification of camphor darkened some time
after the injection. Moreover, a large proportion of the frogs recover-
ing from the camphor intoxications shed their skins irrespective of the
variety of camphor used.
It was found that the abdomens of the frogs recovering from the
camphor intoxications were greatly distended and that if the abdomen
were compressed the frog could be caused t-o urinate, pointing to a
tonic contraction of the cloacal sphincter and to a consequent retention
of urine. In this regard no difference could be detected in the frogs
treated with dextro- or laevo- camphor.

EXPERIMENTS WITH WHITE RATS

My experiments on the relative toxicity of dextro- and laevo-cam-

phor were also carried on with mammals using white rats as test animals.
After the work on white rats was well, started it was found that not
enough could be obtained to make the result absolutely conclusive
in so far as the exact fatal dose of each modification is concerned.
The results clearly indicate, however, that the minimal lethal dose of
laevo-camphor is somewhat smaller than that of the dextro-form and
that the former acts more quickly and more powerfully when given
in the same dose. The minimal lethal dose of dextro-camphor is 1.0
mm. per gram of body weight, whereas, 0.8 mm. of laevo-camphor
was lethal.

-.4
 ..

454 W. E. GROVE

TABLE 4

All of those rats were injected under the skin of the back with a 10 per cent solution of
dextro-camphor in pure olive oil

z 0 OElI ZZ,
- ‘4 ‘4O I 5E’
<H’4
! DH’ 0
zt;
‘4 ‘4 ZR. ER,,l>,
-, E
DATE
00 lI
1909 #{231} Zz - ZZ
-0 O “‘4’4 ‘4R
‘45H5
‘411 ,‘4
5.CEi. .(‘E HE

H:

June 5 87.0 3.00 3.4 10 15 D 14

7 35.0 1.05 3.0 12 12 D 4
8 53.0 1.25 2.5 19 20 D 6
9 71.0 1.40 2.0 17 25 D15
12 100.0 1.50 1.5 3 3 D49.5
24 145.0 1.45 1.0 60 none D33
22 52.0 0.52 1.0 not noted 40 D 5
22 159.0 0.60 1.0 20 28 D21
24 135.0 1.35 1.0 not noted not noted R 24
23 135.0 1.08 0.8 20 50 R24

TABLE 5

All these rats were injected under the skin of the back with a 10 per cent solution of
laevo-camphor in pure olive oil

HI
‘ON

DATE lIE
0
1909
0
SR
5-

June 8 45.0 1.12 2.5 a 5 D 2.5

9 52.5 1.05 2.0 3 5 D15
12 56.5 0.85 1.5 2 2 i D 0.25
12 68.0 0.68 - 1.0 5 5 D46
15 95.0 0.76 0.8 a 7 D23
24 162.0 1.13 0.7 not noted not noted R 24
22 145.0 0.72 0.5 14 15 R24
22 162.0 0.48 0.3 10 not noted R 24
 TOXICITY OF CAMPHORS 455

It will be Iloted from these tables that mammals are more sus-
ceptible to camphor of both modifications than frogs, the minimal
lethal dose iii both cases being only one-third ofthat for frogs. Whether
this is due to a greater susceptibility of mammals, or to better
absorption or to a less rapid excretion of the drug cannot at present
be stated. Although for rats no great difference in the minimal
lethal dose of the two modifications could be shown, nevertheless, the
laevo-modification acts much more quickly and powerfully than the
dextro-camphor in the same dose. The convulsions come on much
more rapidly, are very much more severe and death ensues more
rapidly. The differences in pharmacological action between the two
modifications is merely one of degree. No qualitative differences were
made out.
The pharmacological action of all the camphors is principally
upon the central nervous system. The action is one of stimulation
from the beginning. At a variable time after the injection, depend-
ing upon the size of the animal and the amount of camphor injected,
the animal experiences convulsions. At first these are very slight
shaking movements which involve the entire body. Very early a
trisinus sets in as is evidenced by the grinding of the teeth. As the
convulsions become more and more severe they take on more and more
the characteristics of an opisthotonus. The animal lies on its belly
with legs stretched out, head stretched back and tail arched over its
back. The convulsions are entirely clonic in character. At times
there appear alternate contractions of the two sides of the body,
throwing the rat from side to side. This type of convulsion is pro-
duced alike by both modifications of camphor. During the convul-
sions the breathing is very rapid. Later, as the number of convul-
sions decreases, the breathing becomes slower and slower and death is
finally caused by failure of the respiration. The heart may continue
to beat for a time after cessation of the respiration. As in the case of
frogs it was noted in the rats which lived a considerable time that the
bladder was distended with urine, pointing probably to a tonic spasm
of the sphincter of the bladder.
Microscopic examination of the tissues of rats poisoned with dextro-
and laevo-camphor showed nothing beyond a considerable degree of
hemorrhage into the tissues and a condition of parenchynmatous degen-
eration in the viscera.
456 W. E. GROVE

CONCLUSIONS

1. The minimal lethal dose of dextro-camphor for frogs lies between

3.1 and 3.2 miii. per gram of body weight.
2. The minimal lethal dose of laevo-camphor for frogs is 2.3 mum.

per gram of body weight.

3. The minimal lethal dose of synthetic racemic camphor is approxi-
mately 2.7 mm. per gram of body weight.
4. The toxicological action of dextro-camphor differs fiom that of
the laevo-form principally in degree and not in kind.
5. The action of dextro- amid laevo-camphor is primarily upon the
central nervous system. In the case of mammals the camphors
first stimulate and finally paralyze the central nervous system, while
in frogs the preliminary stimulating stage is not marked except when
the laevo-forni is used.
6. Death is caused by all the modifications of camphor by ParalYsis
of respiration.
7. Mammals are about 3 times as susceptible as frogs to the action of
all modifications of camphor.

I wish to take this opportunity of expressing immy thanks to Prof.

Edward Kremers of this University for kindly placing at my dispoSal
the preparations of camphor used, and to Prof. A. S. Loevenhart, in
whose laboratory this work was carried on, for his continued interest
and helfpul suggestions.