The object of these experiments was to determine the minimum fatal
dose for the gray rabbit and to obtain additional evidence as to
the toxicity of caffein in the several varieties of rabbits. Eight
experiments were performed, in which from 236 to 252 mg per kilo were
given. The white rabbits, three in number, received 250, 242, and 238
mg per kilo. All the others (which were Belgian hares) received from
236 to 252 mg per kilo. Two of the white rabbits were fed carrots for
one week preceding the injection of caffein. The other was fed oats.
Three of the Belgian hares were on a diet of oats, two were fed carrots
the week before the experiment with caffein.
_Rabbit 122. White, female. Weight, 2,060 grams. Diet, oats._
April 14: 25 cc of 2 per cent caffein (250 mg per kilo) in aqueous
solution injected subcutaneously in the back at 1.35 p. m.; 4.30 p. m.,
tremors, reflexes increased, condition otherwise good.
April 16: 9 a. m., found dead in cage. _Autopsy_: Liver deeply
congested; kidneys congested in cortex and medulla; stomach showed
small hemorrhagic areas, perforating ulcers in pyloric portion; small
intestine petechiated on mucosa; lungs and spleen normal.
_Rabbit 234. White, female. Weight, 1,650 grams. Diet, November 2-9,
carrots._
November 9: 10.45 a. m., 20 cc 2 per cent caffein (242 mg per kilo)
administered subcutaneously.
November 10: 9 p. m., found dead.
_Rabbit 335. Gray hare, female. Weight, 1,170 grams. Diet, March 31 to
April 7, carrots._
April 7: 9.30 a. m., 14 cc 2 per cent caffein solution (240 mg per
kilo) injected subcutaneously in the back; 10.30, reflexes much
increased, rabbit is extremely sensitive.
April 8: 9 a. m., found dead. _Autopsy_: Liver was congested and
contained several coccidiosis nodules; stomach distended with rather
dry food mass; mucosa exhibited mild catarrhal inflammation; mucosa of
intestines also slightly inflamed.
_Rabbit 249. Belgian hare, female. Weight, 1,185 grams. Diet, oats._
November 11: Urine, 5 cc, from bladder acid to litmus, no sugar,
no albumin; 11.50 a. m., 14 cc 2 per cent caffein (236 mg per
kilo) administered subcutaneously; 3.45 p. m., reflexes increased,
hyperæsthesia marked, but no tetanus, even when handled; 30 cc urine
collected at 4 p. m., reduction of Fehling's solution considerable.
November 12: 10 a. m., 8 cc urine collected, reduction heavy, only a
few cubic centimeters obtained from bladder, did not contain any sugar,
general condition of rabbit good, no symptom of caffein intoxication.
_Rabbit 321. Yellow, female. Weight, 1,135 grams. Diet, oats._
March 16, 1910: 11.50 a. m., 14 cc 2 per cent caffein (246 mg per kilo)
injected subcutaneously in the back; 2 p. m., reflexes increased, is
very sensitive, started to run when put on floor, no handling except
what was required for removal and return to cage, feces soft.
March 17: 9.30 a. m., condition good, rabbit put on floor, gait normal,
but does not care to walk.
March 18: 9 a. m., walks around when put on floor, appetite good,
condition seems to be normal.
March 25: 11 a. m., rabbit still alive, condition good.
_Rabbit 250. Belgian hare, female. Weight, 1,435 grams. Diet, oats at
least two days before the experiment._
November 11: 11 a. m., urine obtained from bladder acid to litmus, no
albumin, no sugar; 11.10 a. m., 18 cc, 2 per cent caffein (252 mg per
kilo); 3.45 p. m., reflexes and hyperæsthesia, no tetanus; 4 p. m., 60
cc urine, marked reduction of Fehling's solution.
November 12: 10 a. m., condition of rabbit good, no symptoms of caffein
intoxication, 80 cc urine collected, sugar considerable, only a few
cubic centimeters of urine obtained from bladder, no reduction of
Fehling's solution.
_Rabbit 834. Belgian hare, female. Weight, 1,270 grams. Diet, carrots,
March 31 to April 7._
April 7: 9.30 a. m., 15 cc 2 per cent caffein (240 mg per kilo)
injected subcutaneously in the back; 10.30 a. m., reflexes much
increased, rabbit extremely sensitive.
April 8: 9 a. m., condition good, no symptoms.
_Rabbit 233. White, male. Weight, 1,675 grams. Diet, carrots, November
2 to 9._
November 9: 10.50 a. m., 20 cc 2 per cent caffein (238 mg per kilo)
injected subcutaneously, no symptoms observed until 5 p. m., when
increased reflexes and hyperæsthesia were noticed, but no tetanus.
November 10: 9 a. m., paralysis of posterior extremities; died at
1 p. m.
Analysis of the results obtained in the experiments of this series and
inspection of Table I, page 25, show that all four of the rabbits which
survived doses of 236 to 252 mg of caffein per kilo were Belgian hares.
Of the four which died one only was a Belgian hare. The other three
were white rabbits. Two of these were fed oats; the other two received
carrots during seven days preceding the administration of caffein.
This diet does not seem to be a factor, therefore, in the toxicity of
caffein. Moreover, it may be observed that rabbit No. 122, which was
fed oats, died after receiving 250 mg per kilo, while rabbit No. 250
received the same diet and survived the same dose of caffein per kilo.
Experiments 234 and 334 offer another illustration that the toxicity
of caffein is not dependent upon diet, since both rabbits were fed
carrots, but the same dose of caffein caused only symptoms in one
while it proved fatal to the other. It is evident, therefore, that
the difference in resistance to caffein shown in these experiments is
in all probability due to race, the Belgian hare being more resistant
to caffein than rabbits of other varieties. Rabbit No. 335 seems to
be an exception, but the post-mortem examination showed the presence
of coccidiosis of the liver. As will be shown later, wherever this
condition prevailed even smaller doses of caffein proved fatal.