46 THE TOXICITY OF CAFFEIN. 



reason to suppose, however, that the varieties experimented upon in the summer 

 were more resistant than those used in the winter and spring. It is highly probable, 

 therefore, that the greater resistance to caffein of the guinea pigs of series C than those 

 of series B was due to seasonal variation. 



Doses of 0.20 to 0.24 gram caffein per kilo weight, therefore, may be regarded as the 

 minimum fatal dose for the guinea pig, depending upon the season. Since 0.2 gram 

 per kilo proved to be rapidly fatal in series B, this quantity was perhaps not the 

 minimum fatal dose for the guinea pig at the season during which the experiments 

 were made. Additional tests with smaller doses were therefore carried out during 

 February and March. The results are shown in series D. 



SERIES D. 



Guinea pig 49. Male. Weight, 510 grams. Diet, oats for 1 month previous to experi- 

 ment. 



March 17: 3 p. m., 4 cc 2 per cent caffein (0.16 gram per kilo) were injected sub- 

 cutaneously; 4.40 p. m., reflexes increased; 5.40 p. m., no symptoms. 

 .- March 18: 9 a. m., found dead, died in less than 18 hours. Autopsy: Hemorrhage 

 into abdominal cavity; liver and spleen unduly congested; intestines injected; 

 hemorrhagic area at point of injection. 



Guinea pig 40. Male. Weighty 630 grams. Diet, oats and carrots one week previous to 

 injection. 



February 12: 11 a. m., 5 cc 2 per cent caffein (0.158 gram per kilo) injected subcu- 

 taneously into back. 



February 13: 1 p. m., still alive. 



February 14: 9 a. m., found dead. 



Guinea pig 45. Female. Weight, 435 grams. Diet, oats for about one month previous to 

 injection. 



March 17: 3 p. m., 3.5 cc of 2 per cent caffein injected subcutaneously in the back 

 (0.160 gram per kilo); 4.35 p. m., no symptoms; 5.40 p m., no symptoms. 

 Guinea pig 39. Male. Weight, 820 grams. Diet, oats and carrots. 



February 12: 11 a. m., 6 cc (0.15 gram per kilo) 2 per cent caffein injected subcu- 

 taneously in back. 



February 14: 9 a. m., alive; seemed to be in good condition; found dead at 1 p. m. 

 Guinea pig 41 Weight, 660 grams. Diet, oats and carrots one week previous to injection- 



February 12: 11 a. m., 5 cc (0.15 gram per kilo) 2 per cent caffein injected subcu" 

 taneously. 



February 14: 2 p. m., pig alive; apparently normal. 



February 18: Guinea pig still alive and apparently in good condition. 

 Guinea pig 46. Female. Weight, 470 grams. Diet, oats about one month previous to 

 experiment. 



March 17: 3.15 p. m., 4 cc (0.170 gram per kilo) 2 per cent caffein injected into back 

 subcutaneously; 4.35 p. m., reflexes increased, tremors on handling marked; 5.40 p. 

 m., no change, symptoms about as before. 



March 18: 2.30 p. m., no symptoms. 



The experiments of this series (D) likewise showed a considerable difference in the 

 resistance of the individual guinea pigs. Nos. 41, 45, and 46 survived; the rest of 

 the pigs died within 18 hours to 2 days after the administration of caffein. Since an 

 autopsy was held on one only, it is impossible to assign a cause for the variation in the 

 toxicity of caffein in these guinea pigs, as the diet and the other conditions under 

 which the experiments were conducted were the same. It was found in the experi- 

 ments on cats and rabbits that the presence of morbid processes tends to increase the 

 toxicity of caffein. The observations of Ophiils 66 are of interest in this connection. 

 He found spontaneous lesions of the kidney and liver in a large proportion of guinea 

 pigs examined. The greater susceptibility to caffein of guinea pigs Nos. 39, 40, 49, 

 is probably due therefore to some pathological change which increased its toxicity. 

 About 0.2 to 0.24 gram per kilo may therefore be regarded as the minimum lethal 

 dose for the normal guinea pig when caffein is introduced subcutaneously, the mini- 

 mum toxic dose being about 150-160 mg per kilo. 



