DISCUSSION OF RESULTS. 91 



in this connection, that the symptoms of caffein intoxication in young dogs often 

 presented marked differences from those observed in those of more advanced age. 

 The resemblance of the effects of caffein in young puppies and in rabbits was very 

 striking. In both, the tonic with clonic convulsions were observed after a sufficient 

 quantity of caffein was administered. In the dogs which were fully grown a large 

 dose of caffein was usually followed by tonic convulsions and almost instantaneous 

 death. 



Moderately large amounts of caffein fed daily to puppies for several days in some 

 cases as long as 10 days induced mild symptoms only. No cumulative effect was 

 observed in any of the experiments of series C. There seems to be tolerance of certain 

 functions toward caffein, but no general tolerance of the body could be obtained in 

 these experiments. Caffein is apparently less toxic for adult dogs on high than on low 

 protein diet. In young and growing dogs caffein is somewhat less toxic when milk, 

 rather than meat, forms the exclusive diet. Some pathological conditions apparently 

 increase the toxicity of caffein also in dogs. The symptoms of caffein intoxication 

 observed in young dogs are in some respects different from those in full grown and older 

 animals, and resemble those noticed in rabbits. 



DISCUSSION OF RESULTS. 



It was pointed out at some length in the introduction that the 

 toxicity of some drugs may not be the same for all forms of life. 

 This observation was also made by some investigators who experi- 

 mented with caffein on different species of animals. Thus Maurel 55 

 stated that caffein is twice as toxic for the frog as for the rabbit when 

 administered by mouth. Frohner's 28 experiments, on the other hand, 

 made on domestic animals, failed to show great differences in the 

 toxicity of caffein. According to this observer, horses seem to be 

 more susceptible than cattle, goats, and swine, the minimum toxic 

 dose being the same for all of these, while the resistance of the dog to 

 caffein is about midway between that of the horse and the other 

 animals mentioned. It may be remarked, however, that Frohner made 

 only 13 experiments. That these data are inadequate for the forma- 

 tion of any conclusions as to the toxicity of caffein is evident since 

 the most striking effect of caffein observed in the work herein 

 reported was the comparatively wide range of variation in the re- 

 sistance of individuals of the same species to this drug. This was 

 found to be the case even when the conditions of experimentation 

 were approximately uniform, and was observed whatever the mode 

 of administration of the drug employed. The toxicity for different 

 individuals also varied in acute as well as in chronic intoxication. 

 It is for this reason that the number of tests employed were often 

 quite large, for no conclusions of any value could be drawn without 

 averaging the results of a sufficiently large number of experiments. 

 Furthermore, it is to be borne in mind that the action of a drug may 

 differ according to the mode of its introduction into the body and 

 that different species of animals may vary in this regard. This is 

 especially true of some substances when given by mouth, the range 



