CONCLUSIONS. 95 



statement in the introduction it is evident that the size of the single 

 toxic or lethal dose of a substance is in no wise an index of the active 

 degree of its toxicity. The experiments with caffein here reported 

 furnish additional evidence that this is true, at least for the rabbit. 



GENERAL SUMMARY AND CONCLUSIONS. 



The toxicity of caffein in the rabbit varies with the mode of its 

 administration, being least when given by mouth and greatest by 

 intravenous administration. The toxicity is from 15 to 20 per cent 

 greater by subcutaneous injections than by mouth, but is about half 

 of that when injected into the peritoneal cavity. No difference was 

 observed in the toxicity of caffein whether administered into gluteal 

 or into the lumbar muscles. When introduced by this route the 

 toxicity was found to be less by one- third than when it is injected 

 into the peritoneal cavity, but is about 30 per cent more toxic than 

 the subcutaneous injections. White or black rabbits were found to 

 be less resistant to caffein than gray rabbits. 



The resistance of the guinea pig to caffein, as of the rabbit, is 

 greatest when given by mouth. The minimum fatal dose is less by 

 intraperitoneal injections, but greater than by subcutaneous injec- 

 tions, thus differing from the rabbit in this regard. The adult cat 

 is less resistant than the guinea pig or rabbit to caffein. The mini- 

 mum lethal dose by mouth is the same as by subcutaneous, and is 

 less than by intraperitoneal, injection. The minimum fatal dose 

 for dogs was found to be the same by mouth as by subcutaneous in- 

 jection and is almost the same as for the cat. The toxicity of caffein 

 varies in the guinea pig according to season of the year. 



Age is likewise a factor in the toxicity of caffein, young animals 

 being more resistant than the full-grown and older animals; this was 

 shown in experiments on rabbits, cats, and dogs. The symptoms of 

 caffein poisoning also were different in puppies and in full-grown dogs. 

 Different diets, such as carrots and oats, did not influence the resist- 

 ance of rabbits and guinea pigs to caffein. Low protein diet tends 

 to decrease resistance to caffein in dogs. Young growing dogs are 

 less resistant to caffein on a meat than on a milk diet. Caffein is 

 not cumulative in the rabbit or dog, even if administered for a con- 

 siderable length of time. Some degree of tolerance may be induced 

 in the rabbit under certain conditions, but not in dogs under the 

 conditions of the experiments made in this investigation. The possi- 

 bility, however, that dogs may acquire tolerance for caffein is not 

 excluded. Although the rabbit tolerates a much larger single dose 

 of caffein than the dog, it was found, in experiments on chronic 

 intoxication that the rabbit is less resistant to caffein than the dog. 

 The toxicity of caffein is probably increased under pathological con- 



