The object of these experiments was to determine the minimum fatal dose
of caffein in the two varieties of rabbits, the white and the gray. All
of the animals selected were approximately of the same weight.
_Rabbit 239. Belgian hare, male. Weight, 935 grams. Diet, oats._
November 19: 4 p. m., 17 cc 2 per cent caffein (363 mg per kilo)
administered by mouth, followed by 10 cc of 0.9 per cent salt solution.
November 20: Urine examined, no sugar found, no symptom noticed at any
time after injection.
_Rabbit 254. Belgian hare, female. Weight, 975 grams. Diet, oats._
November 19: 4.05 p. m., 18 cc 2 per cent caffein (369 mg per kilo)
administered by mouth, followed by 10 cc of 0.9 per cent salt solution.
November 20: 9 a. m., rabbit found dead.
_Rabbit 267. White. Weight, 1,050 grams. Diet, oats._
November 23: 12.10 p. m., 18 cc 2 per cent caffein (342 mg per
kilo) given by mouth, followed by 18 cc salt solution; 1 p. m.,
increased reflexes, tremors marked but no tetanus; 1.05 p. m., rabbit
stretched on abdomen, posterior extremities in extended position and
paralyzed, soon after clonic spasms set in, which recurred about every
minute; 1.14 p. m., tetanus and death. _Autopsy_: Liver showed fatty
degeneration; slight inflammation of stomach and intestines; other
organs normal.
_Rabbit 268. White. Weight 1,100 grams. Diet, oats._
November 23: 20 cc 2 per cent caffein (363 mg per kilo) administered
by mouth, followed by 20 cc salt solution; 1.15 p. m., somewhat
hypersensitive; 4.30 p. m., tremors fairly marked, no urine passed,
about 2 cc of bloody looking urine obtained from bladder, which
contained albumen and a considerable amount of glycogen; rabbit died.
_Rabbit 419, Belgian hare, male. Weight, 1,600 grams. Diet, oats._
September 26: 10 a. m., 28 cc 2 per cent caffein (350 mg per kilo)
given by mouth; reflexes increased at 4 p. m.; 6 p. m., reflexes still
increased, no other symptoms.
September 27: 9 a. m., found dead. _Autopsy_: Lungs, liver, and kidneys
congested; other organs normal.
_Rabbit 420. Belgian hare, male. Weight, 1,250 grams. Diet, oats._
September 26: 10 a. m., 22 cc 2 per cent caffein (352 mg per kilo)
given by mouth; 11.35 a. m., convulsions; 12 noon, found dead.
_Autopsy_: Liver showed very extensive coccidiosis; no other lesions.
_Rabbit 421. Belgian hare, male. Weight, 1,485 grams. Diet, oats._
September 26: 10 a. m., 26 cc 2 per cent caffein (351 mg per kilo)
administered by mouth; 4 p. m., reflexes increased; 6 p. m., reflexes
as before, no tetanus observed.
September 27: 9 a. m., rabbit found dead. _Autopsy_: Congestion of
lungs and kidneys; liver congested and slightly fatty.
_Rabbit 424. White, male. Weight, 1,295 grams. Diet, oats._
September 26: 2 p. m., 19 cc 2 per cent caffein (293 mg per kilo)
administered by mouth; 4 p. m., reflexes increased, no other symptoms;
6 p. m., no change since 4 p. m.
September 27: 12 noon, convulsions and death. _Autopsy_: Congestion of
the lungs; no other lesions.
_Rabbit 423. White, male. Weight, 1,205 grams. Diet, oats._
September 26: 2 p. m., 18 cc 2 per cent caffein administered by mouth;
4 p. m., reflexes increased, no tetanus; 6 p. m., condition unchanged
since 4 p. m.
September 27: 9 a. m., found dead. _Autopsy_: Lungs, liver, and kidneys
congested; other organs normal.
_Rabbit 422. White, male. Weight, 1,440 grams. Diet, oats._
September 26: 2 p. m., 21 cc 2 per cent caffein (291 mg per kilo) given
by mouth; reflexes increased at 4 p. m.
September 27: 3 p. m., alive, no symptoms; 4 p. m., convulsions with
recovery, this was soon followed by a violent attack of tetanus, which
lasted about one minute and was succeeded by paralysis; rabbit died
at 4.30. _Autopsy_: Liver slightly congested; a small portion of the
intestine showed congestion and edema; other organs normal.
A study of these experiments shows also considerable variation in the
toxicity of caffein when given by mouth. In some cases a dose of 300
mg per kilo, and even less, caused death, as in rabbits 423 and 424.
In other rabbits, however, approximately the same doses of caffein
produced increased reflexes only. The same symptoms were produced in
Nos. 248 and 249 after the administration of 325-330 mg of caffein
per kilo, while another rabbit (No. 239) survived a dose of 363 mg
per kilo. That this is exceptional, however, appears from the result
of the following experiments on rabbits Nos. 419, 420, and 421, all
of which died after receiving 350 mg of caffein per kilo, and rabbits
267 and 268, to which doses of 363 and 342 mg, respectively, per kilo
proved fatal. It will be observed further that the gray rabbits are
more resistant to caffein than the white animals, as 350 mg per kilo
was the smallest fatal dose for rabbits 419, 420, and 421, all of which
were gray rabbits, while a dose of 290 mg per kilo was fatal for some
of the white rabbits. Again, it will be noticed that of the two gray
rabbits, Nos. 254 and 239, which received the largest doses in these
experiments, namely, 369 and 363 mg, respectively, one survived. The
largest doses given to the white rabbits were 363 and 342 mg caffein
per kilo. Both of these died from the effects of the drug. It may be
concluded, therefore, that the minimum toxic dose for the gray rabbit
is about 325 mg of caffein per kilo, and the minimum fatal dose is at
least 350 mg per kilo. It is to be remarked in this connection that
post-mortem examination showed extensive coccidiosis in rabbit 420
and fatty liver in No. 421, while the macroscopical examination of
the organs of Nos. 424 and 423 failed to show the presence of such
abnormalities. Since, as was observed in the section on subcutaneous
injection and elsewhere in this investigation, pathological changes are
apt to decrease the resistance to caffein, it is quite possible that
350 mg per kilo is not the minimum fatal dose for the normal rabbit.
Indeed, the experiment on rabbit 239 lends support to this view, thus
furnishing additional evidence of difference in the resistance to
caffein in the two varieties of rabbits.