60 THE TOXICITY OF CAFFEIN. 



caffein per kilo (Nos. 93 and 87) salivation in one cat (No. 93) and irritability and 

 muscular stiffness in the other were the only effects noticed. These symptoms were 

 no longer observed the next day and the cats appeared to be perfectly normal. Experi- 

 ments with larger doses indicate that the minimum fatal dose by this method of 

 administration is about 0.2 gram per kilo. 



EXPERIMENTS ON DOGS. 



The experiments were carried out on well-fed adult dogs and on puppies, kept 

 under observation for some time before the drug was administered. Only those 

 manifesting no signs of abnormality were used for these tests. Caffein was given by 

 mouth mixed with 10 to 20 grams of meat, or subcutaneously in 2 per cent aqueous 

 solution. The young animals received caffein dissolved in milk. The determination 

 of the minimum toxic or fatal doses when the drug was fed presented considerable 

 difficulty, as in many instances the ingestion of the drug was closely followed by 

 vomiting. 



ADMINISTRATION BY MOUTH. 



SERIES A. 



The effective dose in these experiments showed considerable variation. One dog 

 (No. 38) died after a dose of 0.12 gram caffein per kilo, while some subjects survived 

 doses of 0.2 and 0.23 gram per kilo. In the 12 experiments given in Table 12, page 62, 

 it will be noticed that from 0.12 to 0.152 gram per kilo proved fatal to three dogs, 

 while three others survived the same amounts in proportion to the body weight. The 

 results were the same with larger doses. It may be observed in this connection that 

 in the case of the five dogs in which vomiting was noticed some time during the 24 

 hours following the administration of caffein, four survived, No. 38 being the exception. 

 The greater toxicity of caffein in this case is in all probability due to some morbid 

 process, the presence of which was indicated by the high temperature of this subject. 



That vomiting may avert a fatal issue after larger doses of caffein is made further 

 probable by experiment on dog No. 48, for which, in the absence of vomiting, a dose of 

 0.2 gram of caffein per kilo proved fatal. On this supposition the discrepancy in the 

 results obtained in this series may be readily explained. The smallest doses which 

 proved fatal in these experiments were 0.145 and 0.152 gram per kilo. No. 38, which 

 died from a dose of 0.12 gram per kilo, may be considered as an exception, as this subject 

 was not normal. Experiments with caffein on dogs were made at various other times 

 in this laboratory but failed to show that smaller doses of caffein, even when vomiting 

 did not occur after its administration, were fatal, although toxic effects were observed. 

 The conclusion is therefore justified that the minimum fatal dose of caffein for the 

 normal dog is about 0.15 gram per kilo when given by mouth. 



SUBCUTANEOUS INJECTION. 



SERIES B. 



To determine the toxicity of caffein more accurately, especially for comparison 

 with animals of other species, the subcutaneous method of administration was also 

 used. The injections were made with a syringe of 20 cc capacity, the contents of 

 which were introduced into contiguous areas. The results of experiments on six 

 dogs indicate that approximately 150 to 160 mg per kilo is the minimum fatal dose, 

 since such doses proved fatal to two out of the three animals receiving this amount, 

 while three others which received doses of from 143 to 160 mg per kilo survived. 



