24 THE TOXICITY OF CAFFEIN. 



engorged and friable; gall cyst well filled; stomach exhibited catarrhal gastritis; injec~ 

 tion of mesenteries and intestines; kidney showed marked cortical congestion. 



The results of the experiments of this series likewise indicate that the Belgian 

 hare is more resistant to caffein than the rabbits of other varieties. Thus, of the four 

 gray rabbits (Nos. 235, 316, 395, and 396), which received 267 to 283 mg of caffein per 

 kilo, two died and two lived, o one of which, 396, showed the presence of coccidiosis 

 of the liver. On the other hand it will be observed that the black and white rabbits 

 which received from 270 to 275 mg of caffein per kilo all died from the effects of the 

 drug; one within 1 hour and 25 minutes and another within 50 hours after the admin- 

 istration of the caffein, while No. 340 died in the night. Furthermore it will be noted 

 that of the last three rabbits of this series, which were Belgian hares and received 

 290, 293, and 300 mg of caffein, two died six hours after the injection, while the other, 

 No. 397, lived three days. The minimum fatal dose of caffein for Belgian hares is, 

 therefore, about 290 to 300 mg per kilo when injected subcutaneously, which is about 

 50 per cent greater than for rabbits of other varieties. 



SERIES E. 



It was shown in series A that 0.15 caffein per kilo caused symptoms of intoxication. 

 Before concluding, however, that this is the smallest dose which causes symptoms of 

 poisoning, a number of experiments were performed with smaller doses. It was 

 found that in the great majority of cases 0.1 caffein per kilo may cause diuresis, 

 but no nervous or muscular symptoms. In some rabbits, however, even such a dose 

 proved fatal. Post-mortem examinations in these cases showed the presence of 

 coccidiosis of the liver, and it will be recalled that similar observations were made 

 before. It is quite possible, therefore, that coccidiosis of the liver is an important 

 factor in decreasing the resistance to caffein. Experiment 551 (p. 25) shows that 

 other conditions may likewise increase the toxicity of caffein. 



Rabbit 825. White, female. Weight, 1,065 grams. Diet, oats. 



March 17: 11 a. m., 6 cc 2 per cent (112 mg per kilo) caffein injected subcutaneously 

 in the back. About 5 cc of urine squeezed out from bladder before injecting caffein. 



March 17: 1 p. m., hind legs crossed and stretched out, front legs also extended; 

 rabbit lying stretched out on her belly. 



March 17: 5.40 p. m., rabbit still alive, condition somewhat improved. 



March 18: 9 a. m., found dead, stiff and cold. Autopsy: Hemorrhagic area at point 

 of inoculation; subcutaneous region of both thighs presented a hemorrhagic infiltra- 

 tion of the tissues; liver contained lesions of coccidiosis; other organs apparently 

 normal. 

 Rabbit 330. Belgian hare, female. Weight, 935 grams; poorly nourished. 



March 18: 3.35 p. m., 5 cc 2 per cent caffein (107 mg per kilo) injected into subcu- 

 taneous tissues in the back; 5.30 p. m., no symptoms. 



March 19: 9 a. m., no symptoms. 



March 25: Weight, 825 grams. 



Rabbit 329. Belgian hare, male. Weight, 775 grams; poorly nourished. Received 

 March 18. 



March 18: 3.30 p. m., 4 cc 2 per cent caffein (103 mg per kilo) injected into sub- 

 cutaneous tissues in the back; 5.30 p. m., no symptoms. 



March 19: 9 a. m., no symptoms. 



March 25: Rabbit alive in good condition; weight, 825 grams. 

 Rabbit 320. Black, male. Weight, 1,040 grams. Diet, oats. 



March 17: 11 a. m., 6 cc 2 per cent caffein (115 mg per kilo) injected subcutaneously 

 in the back; only a few drops of urine obtained from bladder before injecting caffein; 

 1 p. m., rabbit very restless; ran away when placed on floor; cried when touched with 

 a piece of paper; no tremors observed, but rabbit became exhausted and was unable 

 to walk; legs extended out; after running for about a minute dyspnoea was very 

 marked, but rabbit soon raised himself on his legs; 5.40 p. m., rabbit up on his legs. 



<* Survived first dose. 



