94 THE TOXICITY OF CAFFEIET. 



adult. This is not true, however, for the young of other species. 

 Cats under 15 days of ^age tolerate twice the toxic dose of morphin 

 for the adult cat. Young beeves and goats are likewise more resistant 

 to this alkaloid than adults. On the other hand, according to Livon, 54 

 young guinea pigs are more sensitive to alkaloids than adults. The 

 toxicity of caffein, as shown in the present investigation, was found 

 to be less in the young than in the adult. In dogs the young subjects 

 are hi some instances almost twice as resistant as adults. The differ- 

 ence was found to be less in cats and rabbits than in dogs, but it was 

 quite marked. 



The effect of season on the toxicity of drugs has been discussed in 

 the section on the experiments on guinea pigs, which were more re- 

 sistant to caffein in the fall than in February and March. The effect 

 of season seems to vary with the animal, but it may also differ with the 

 substance employed. In Noe's 65 studies on this subject cantharidin 

 was found to be more toxic for the hedgehog in November than in 

 July. The effect of season was different for morphin, as it was 

 observed that the resistance of the hedgehog was greater at the end 

 of the summer than earlier in the season. 



The relation of diet to toxicity of drugs has been studied by Hunt. 39 

 His experiments indicate that this is an important factor in the resist- 

 ance to acetonitril. The studies here reported on the effect of diet 

 on toxicity of caffein in rabbits were confined to experiments with 

 oats and carrots and do not show any modification of the resistance 

 to caffein. The question of diet in chronic intoxication in dogs, how- 

 ever, suggests that in these animals diet may affect the toxicity of 

 caffein, although the data on this subject are* far from satisfactory. 

 There is nevertheless sufficient evidence to suggest that a high protein 

 diet for the adult dog tends to greater resistance of the animal to 

 caffein and similarly the growing dog tolerates larger quantities of 

 caffein on a milk diet than on a diet of meat. 



This brings us to a consideration of the behavior of caffein in 

 chronic intoxication. Although in both rabbits and dogs absence of 

 cumulation was evident, in other respects decided differences in the 

 resistance to caffein were observed. While the rabbit tolerates more 

 than twice the single dose of caffein per kilo for the dog, the result is 

 quite different in repeated dosage of the drug, the rabbit succumbing 

 to continued administration of much smaller doses of the drug than 

 the dog. This is probably due to lesions of the gastro-intestinal canal 

 caused by caffein which occasions loss of appetite much more readily 

 in the rabbit than in the dog. The abundant energy reserve in the 

 dog makes it possible for this animal to stand inanition much longer 

 than the rabbit and other herbivora. The difference in the behavior 

 of the rabbit and dog toward caffein is interesting as showing complete 

 reversal of resistance in acute and chronic intoxication. From the 



