TOXICITY OF CAFFEIN IN NEPHRECtOMIZED RABBITS. 23 



this method it was thought the total quantity introduced could be 

 increased without producing fatal consequences. Series II and III 

 show the result of this treatment. 



Rabbit 797. Gray male; weight, 1,740 grams. 



May 3: 2 p. m., double nephrectomy; 3.30 p. m., 9 cc of 2 per cent caffein injected 

 Bubcutaneously; 5.30 p. m., somewhat hypersensitive. 



May 4: 8.25 a. m., reflexes increased, condition otherwise good; 11.10 a. m., 11 cc of 

 2 per cent caffein injected subcutaneously ; 12.30 p. m., increased reflexes observed. 



May 5: 10 a. m., condition good, no symptoms; 11 a. m., 17 cc of 1 per cent caffein 



May 6: 9 a. m., condition good, no symptoms; 11 a. m., hypersensitive; 2.15 p.m., 

 died. 



Rabbit 798. Gray female; weight, 1,205 grams. 



May 3: 2.25 p. m., double nephrectomy; 3.35 p. m., 6 cc of 2 per cent caffein 

 injected subcutaneously; 5.30 p. m., slightly sensitive. 



May 4: 8.30 a. m., no symptoms; 11.13 a. m., 8 cc of 2 per cent caffein injected 

 subcutaneously; 12.30 p. m., reflexes increased. 



May 5: 10 a. m., condition good, no symptoms; 11 a. m., 12 cc of 1 per cent caffein 

 injected subcutaneously. 



May 6: 9 a. m., found dead; cold and stiff . 



Total caffein injected, 0.33 gram per kilo. 



Rabbit 799. Gray female; weight, 1,165 grams. 



May 3: 3 p. m., double nephrectomy, attended by considerable loss of blood; 4.35 

 p. m., 6 cc of 2 per cent caffein injected subcutaneously; 5.30 p. m., no symptoms. 



May 4: 9 a. m., no symptoms; weight, 1,080 grams; 10.30 a. m., 8 cc of 2 per cent 

 caffein injected subcutaneously; 12.30 p. m., reflexes increased markedly; 1 p. m., 

 found dead and stiff, body warm. 



Although some of the rabbits of this series became hypersensitive, 

 thus showing symptoms of caffein poisoning after the first dose, there 

 was no evidence of cumulation under the conditions employed in the 

 series, since all of them survived the total amount, which is a fatal 

 dose for the normal rabbit. Rabbit No. 797 was in good condition 22 

 hours after it received the third dose of caffein, thus making a total of 

 0.57 gram or about 327 mg per kilo, figuring on the basis of the initial 

 weight, which would make at least 350 mg per kilo if the loss of weight 

 from day to day is taken into consideration. The same holds true 

 for rabbit No, 798. The case of rabbit No. 799 is probably due to 

 hemorrhage and may be regarded as exceptional, which is made 

 highly probable by the behavior of rabbits Nos. 803, 804, and 805 

 in the following series of experiments 



CUMULATION WITH SMALL DOSES (SERIES III). 



Rabbit 804 White female; weight, 1,755 gram^. 



May 9: 3.25 p. in., double nephrectomy; 4.32 p. m., 9 cc of 2 per cent caffein 

 injected subcutaneously; 5.30 p. m., no symptoms. 



May 10: 12 m., 13 cc of 2 per cent caffein injected subcutaneously; 4.30 p. m., no 

 symptoms. 



May 11: 9 a. m., reflexes increased; weight, 1,630 grams; 2 p. m., reflexes increased; 

 no other symptoms; 8.5 cc of 2 per cent caffein injected subcutaneously; 4.30 p. in., 

 still alive. 



May 12: 11.30 a. m., found dead. 



Rabbit 80S. White male; weight, 1,825 grams. 



