92 THE TOXICITY OF CAFFEIN. 



in toxicity for certain species of animals being much greater when 

 thus administered than when injected subcutaneously or intrave- 

 nously. 



Maurel's 56 investigations are of interest in this connection, as his 

 work embraces a systematic study of the toxicity of a large number 

 of substances in the rabbit, pigeon, and frog when given by mouth, 

 subcutaneously, intravenously, or when injected into the muscles. 

 According to this investigator the range of variation of the toxicity 

 of a substance is widest when given by mouth. Potassium sulpho- 

 cyanid, for example, is about 2.5 times as toxic for the frog as for the 

 rabbit when given by mouth. Quinin hydrobromid is three times as 

 toxic for the frog as for the pigeon, while for the rabbit it is twice as 

 toxic as for the pigeon. When given by hypodermic 'injection the 

 toxic dose per kilo weight is practically the same for all three species. 

 The difference of resistance according to the mode of administration 

 is even more marked for spartein sulphate. When given by mouth 

 the toxicity for the rabbit is six times as great as for the frog, but 

 when injected subcutaneously the toxic dose is about the same for 

 the rabbit and for the frog. The relation of the mode of adminis- 

 tration to toxicity is further shown in the following substances : For 

 the rabbit the minimum fatal dose per kilo of quinin hydrobromid is 

 1.5 grams administered by mouth, 0.5 gram when injected subcu- 

 taneously, and 0.07 gram by the intravenous path, while strychnin 

 sulphate is twice as toxic administered intravenously as subcuta- 

 neously, and six tunes as toxic as when administered by mouth. 

 The mode of introduction, however, does not always affect the 

 toxicity of a substance. This is made evident by the action of 

 strychnin on frogs in which, according to Maurel 56 , the toxic dose is 

 the same whether given by mouth or injected into the subcutaneous 

 tissues. This appears to hold true also for other animals as demon- 

 strated by the experiments of Hatcher 35 on the cat, in which he 

 observed that strychnin is as readily absorbed from a full stomach 

 as from the subcutaneous tissues. These findings are extremely 

 interesting, especially in view of Maurel's 57 work on the subject, 

 according to which he finds that a substance is much less toxic when 

 given by mouth than when administered by hypodermic injection 

 or intravenously. That this generalization does not admit, however, 

 of universal application is made evident by the work of various 

 experimenters. Claude Bernard 10 observed that curara is as poisonous 

 for the pigeon when given by mouth as when injected subcutaneously, 

 while Zalesky M found that samandarin is more toxic for frogs when 

 introduced into the stomach than by injection into the lymph sacs. 

 Our experiments with caffein likewise show that Maurel's generaliza- 

 tion does not always hold good, since it was found in experiments with 

 gray rabbits that the minimum fatal dose is but moderately greater 

 bv mouth than bv the subcutaneous nath. 



