THE TOXIOITY OF CAFFEIN. 



A study of these experiments shows also considerable variation in the toxicity of 

 caffein when given by mouth. In some cases a dose of 300 mg per kilo, and even less, 

 caused death, as in rabbits 423 and 424. In other rabbits, however, approximately the 

 same doses of caffein produced increased reflexes only . The same symptoms were pro- 

 duced in Nos. 248 and 249 after the administration of 325-330 mg of caffein per kilo, 

 while another rabbit (No. 239) survived a dose of 363 mg per kilo. That this is excep- 

 tional, however, appears from the result of the following experiments on rabbits 

 Nos. 419, 420, and 421, all of which died after receiving 350 mg of caffein per kilo, and 

 rabbits 267 and 268, to which doses of 363 and 342 mg, respectively, per kilo proved 

 fatal. It will be observed further that the gray rabbits are more resistant to caffein 

 than the white animals, as 350 mg per kilo was the smallest fatal dose for rabbits 419, 

 420, and 421, all of which were gray rabbits, while a dose of 290 mg per kilo was fatal 

 for some of the white rabbits. Again, it will be noticed that of the two gray rabbits, 

 Nos. 254 and 239, which received the largest doses in these experiments, namely, 369 

 and 363 mg, respectively, one survived. The largest doses given to the white rabbits 

 were 363 and 342 mg caffein per kilo. Both of these died from the effects of the drug. 

 It may be concluded, therefore, that the minimum toxic dose for the gray rabbit is 

 about 325 mg of caffein per kilo, and the minimum fatal dose is at least 350 mg per kilo. 

 It is to be remarked in this connection that post-mortem examination showed ex- 

 tensive coccidiosis in rabbit 420 and fatty liver in No. 421, while the macroscopical 

 examination of the organs of Nos. 424 and 423 failed to show the presence of such 

 abnormalities. Since, as was observed in the section on subcutaneous injection and 

 elsewhere in this investigation, pathological changes are apt to decrease the resistance 

 to caffein, it is quite possible that 350 mg per kilo is not the minimum fatal dose for 

 the normal rabbit. Indeed, the experiment on rabbit 239 lends support to this 

 view, thus furnishing additional evidence of difference in the resistance to caffein 

 in the two varieties of rabbits. 



TABLE 2. Administration of caffein by mouth. 



SERIES A. 



SERIES B. 



INJECTION INTO THE PERITONEAL CAVITY. 



In a number of experiments caffein was introduced into the peritoneal cavity. 

 Rabbits of different varieties receiving a diet of oats or carrots were employed for this 

 purpose; food and water were given ad libitum. The minimum doses required to 

 induce symptoms or cause death in these animals were determined; tests with caffein 

 were also made on young rabbits in order to study the influence of age on the Resistance 

 to this substance. The results are shown in the following experiments: 



