HISTORICAL REVIEW. 17 



caffein sodium salicylate given to the same animal subcutaneously two 

 days previously provoked only very slight symptoms. The sub- 

 cutaneous injection of 10 grams of the same preparation into a pig 

 weighing 30 kilos caused death in two and a half hours, with the pro- 

 duction of symptoms of disturbance of the nervous system and of 

 gastrointestinal irritation. The same dose per kilo of body weight 

 given to a goat likewise caused death in two and a half hours after its 

 administration. Examination on autopsy revealed inflammation of 

 the gastrointestinal tract. Similar lesions were found in a horse 

 killed by 100 grams of caffein, in which he also noticed hemorrhage 

 of the mucosa in the fundus of the stomach. 



Gourewitch M (1907) conducted experiments with caffein on 

 rabbits, pigeons, and white rats. It appears from his protocol that 

 single doses of about 0.2 to 0.25 gram caffein per kilo given subcuta- 

 neously proved to be fatal. He states, however, that the resistance 

 to caffein was markedly diminished, when its administration was 

 repeated daily, for much smaller amounts sufficed to cause death in 

 these animals. A dose of 120 mg of caffein per kilo proved fatal after 

 the third injection. When the dose was increased to 170 mg per kilo, 

 the animal succumbed to the effects of caffein after the second injec- 

 tion. His experiments on the other animals do not indicate the 

 degree of resistance to caffein, since the weights for some were not 

 given while for the others no attempt was made to determine the 

 minimum toxic or fatal dose. 



Maurel 55 (1907) studied the influence of different methods of 

 administration on the toxicity of caffein on frogs and rabbits. He 

 determined the minimum toxic and lethal doses of caffein hydro- 

 bromid which he employed in 1 to 2 per cent solutions. He concluded 

 from his experiments that the toxicity of caffein when given by 

 mouth is twice as great for the frog as for tha rabbit. 



More recently Hale 3J carried out a number of experiments on guinea 

 pigs in which he determined the toxicity of caffein given in the form 

 of the citrate and made into a pill with mucilage of acacia and arrow- 

 root starch. After the pill was dried it was fed to the animal, due 

 precaution being taken that none of it was lost during feeding. 

 From experiments on guinea pigs which received doses of 0.3 to 0.6 

 gram caffein citrate, the following data have been reported : Three 

 decigrams per kilo given to one pig was not fatal. Of three pigs 

 which received 0.4 per kilo, one died and two survived. Exactly 

 the same results were obtained in three others which received 0.5 per 

 kilo. Two guinea pigs, which received 0.55 and 0.6 per kilo each, 

 died after 15 and 7 hours, respectively, while another animal survived 

 a dose of 0.45 per kilo. 



18594 Bull. 14812 2 



