22 THE TOXICITY OF CAFFEIN. 



Rabbit 334- 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 subcutane- 

 ously 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 subcuta- 

 neously, no symptoms observed until 5p.m., when increased reflexes and hyperaesthe- 

 sia 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, there- 

 fore, 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. 



SERIES D. 



To obtain additional evidence regarding the resistance of the various races of rabbits 

 to caffein and to ascertain the smallest dose which is surely fatal to the gray rabbit or 

 Belgian hare was the object of this series of experiments.' The diet in all cases con- 

 sisted of oats, which was given ad libitum excepting to rabbit No. 235, which received 

 carrots for one week previous to the injection of caffein. The doses administered 

 ranged from 267 to 300 mg per kilo and were administered to different varieties of adult 

 rabbits. 



Rabbit 253. Brown and black, male. Weight, 1,600 grams. Diet, oats, November 9 to 12. 



November 12: 11.30 a. m., urine from bladder acid, no albumen, no sugar; 11.35 

 a. m., 22 cc 2 per cent caffein (275 mg per kilo) injected subcutaneously; 11.45 a. m., 

 rabbit jumped* off the table, had convulsions, retraction of head and opisthotonos, 

 general tremors, anterior extremities stretched out, posterior extremities almost 

 normal, frequent twitchings; died at 12.15 p. m. 

 Rabbit 252. Black, female. Weight, 1,335 grams. Diet, oats, November 9 to 12. 



November 12: 11.30 a. m., 18 cc 2 per cent caffein (270 mg per kilo) injected 

 subcutaneously. Urine obtained from bladder before injection, acid, no albumen, 

 no sugar, color normal, tremors and great excitement noticed about 12 noon; 4.30 

 p. m., when handled, showed unusual restlessness and excitement followed by con- 

 vulsions with opisthotonos; occasional twitching, condition bad. Died 4.35 p. m. 

 Rabbit 327. White, female. Weight, 820 grams. Diet, oats, March 8 to 16. 



March 16: 11.45 a. m., 12 cc 2 per cent caffein (292 mg per kilo) injected subcu- 

 taneously in the back; 2 p. m., found dead, but was still warm. Autopsy: Hemor- 

 rhagic area at point of injection into spinal muscles; subcutaneous abdominal region 

 exhibited a large area of cheesy purulent material; liver and spleen were engorged; 

 bladder filled; intestines normal. 

 Rabbit 340. White and brown male. Weight, 1,465 grams. Diet, oats. 



March 30: 3.20 p. m., 20 cc of 2 per cent caffein (273 mg per kilo) injected subcu- 

 taneously in back. 



March 31: 9 a. m., found dead. 



