ACUTE INTOXICATION GUINEA PIGS. 43 



ducing the substance was used. Differences in the toxicity of substances have also 

 been observed between subcutaneous and intravenous modes of administration, 

 but here, too, the differences for various substances were unequal. 



EXPERIMENTS ON GUINEA PIGS. 



The toxicity of caffein was studied in a large number of individuals. The experi- 

 ments were conducted on full-grown animals and were carried out at different seasons 

 of the year in a variety of ways. Special attention was given to diet as a possible 

 factor influencing resistance to caffein, and the effect of different modes of adminis- 

 tration on toxicity. Some animals were therefore fed oats, some carrots, others re- 

 ceived both hay and oats. Caffein was introduced subcutaneously, intraperitoneally, 

 and by mouth. 



SUBCUTANEOUS INJECTION. 



SERIES A. 



Preliminary experiments carried out on three guinea pigs, which received 360, 

 300, and 290 mg of caffein per kilo subcutaneously have shown that such doses were 

 rapidly fatal. Two of the animals were seized with convulsions half an hour after 

 the introduction of caffein and died during the attack. The other had tetanus two 

 minutes after the injection of caffein. Repeated attacks followed, which terminated 

 in the death of the animal two and a half hours later. The fatal and toxic doses must 

 therefore be considerably under 0.3 gram of caffein per kilo when introduced by this 

 path and smaller doses were therefore injected. The results are shown in the experi- 

 ments of the next series. 



SERIES B. 



Experiments with 2 decigrams per kilo constituted this series. 

 Guinea pig 20. Female. Weight, 497 grams. Diet, oats. 



April 2: 5 cc 2 per cent caffein injected subcutaneously at 11.30 a. m.; 1.50 p.m., 

 spasm of short duration. Died at 3 p. m., three and one-half hours after injection. 

 Guinea pig 38. Brown male. Weight, 570 grams. Diet, carrots and oats week previous 

 to injection. 



February 11: 3.50 p. m., 6 cc 2 per cent caffein injected subcutaneously in back 

 (210 mg per kilo); 4.15, reflexes increased, had convulsion of short duration when 

 disturbed; 4.45 p. m., on handling, repeated convulsion and paralysis; 5 p. m., guinea 

 pig lying on his side, respiration difficult and labored. 



February 11: 5.05 p. m., guinea pig found dead, 2 hours and 15 minutes after 

 injection. 



Guinea pig 37. Male. Weight, 820 grams. Diet, carrots and oats during week pre- 

 ceding the injection of caffein. 



February 11: 3.35 p. m., 8.5 cc 2 per cent caffein injected subcutaneously in the 

 back; 5 p. m., pig very sensitive, anterior extremities paralyzed when handled, fre- 

 quent spasms or posterior extremities, no symptoms noticed before 5 p. m., although 

 watched all the time; 5.05 p. m., guinea pig on his legs and looked normal. No attack 

 on handling. 



February 12: 9 a. m., found dead; died within 18 hours. 

 Guinea pig 13. Female. Weight, 618 grams. Diet, oats. 



March 29: 2.45, 6 cc 2 per cent caffein injected subcutaneously (0.194 grams per 

 kilo). 



March 30: Died at 4 p. m., 25 hours after injection. 



Guinea pig 36. Male. Weight, 850 grams. Fed oats and carrots for one week previous 

 to injection. 



February 11: 3.30 p. m., 8.5 cc 2 per cent caffein injected subcutaneously into 

 back; 5 p. m., somewhat more sensitive than normal, no other symptoms, no effect 

 on handling; 5.05 p. m., no symptoms. 



February 12: 9 a. m., found dead, about 18 hours after injection. 



The results of these experiments, as observed in five guinea pigs, indicate that 

 two decigrams of caffein per kilo of animal produce symptoms within a half to about 

 two and a quarter hours after injection . Death followed in, two guinea pigs 70 minutes 



