84 THE TOXICITY OF CAFFEIN. 



October 26: Weight 11.15 kilos. Food consisted of 5 grams cracker meal per kilo; 

 meat, 3 grams per kilo; lard, 2 grams per kilo; tapioca, 10. 69 grams per kilo. Kept in 

 a cold, damp room with poor ventilation until November 20. 



Novembers: Weight, 11 kilos. 



November 10: Weight, 10.75 kilos. 



November 20: Weight, 10.55 kilos; changed to a warm room, with bedding and good 

 ventilation. 



November 29: Weight, 10.85 kilos. 



December 1: Put into a cage. 



December 6: Weight, 10.90 kilos; 11.25 a. m., received 28 cc 2 per cent caffein sub- 

 cutaneously in side, below the shoulders, area washed with alcohol and ether, 

 approximately 50 mg per kilo administered, no symptoms. 



December 7: 10.15 a. m., received 28 cc 2 per cent caffein injected subcutaneously; 

 feces soft and very fetid; 1 p. m., depressed in spirit, eyes dull. 



December 9: 10.45 a. m., received 25 cc 2 per cent caffein solution subcutaneously, 

 feces still fetid, site of injection inflamed and swollen, no other symptoms. 



December 10: Inflammation of area of injection more pronounced; 2 p. m., given 

 0.5449 gram caffein and 30 grams of meat; 4 p. m., fed, no symptoms, feces fetid. 



December 11: 12 m., given 0.5459 gram caffein and 30 grams of meat, no symptoms, 

 feces fetid. 



December 12, 13: Given 0.5459 gram caffein daily, without noticing any symptoms. 



December 14: 12 m., received 0.817 gram caffein (75 mg per kilo); 2.30 p. m., restless 

 and uncomfortable, no other symptoms. 



December 15: 11.30 a. m., received 0.8175 gram caffein by mouth; 2p.m., depressed 

 in spirit, acted as though sick, no other symptoms. 



December 16: Weight, 11 kilos; 11 a. m., received 0.100 gram caffein per kilo (1.100 

 grams) by mouth, no symptoms. 



December 17: Rested. 



December 18: 2.30 p. m., received 1.100 grams caffein by mouth; 4. p. m., no 

 symptoms. 



December 19: 12 noon, received 1.100 grams caffein by mouth; 4.15 p. m., no 

 symptoms. 



December 20: 2.45 p. m., given 1.375 grams caffein (0.125 gram per kilo); 3.45 p. m., 

 vomited one of the capsules being found intact, the other broken open; 4 p. m., 

 given regular diet, containing 1.3757 grams caffein in capsules, ate most of this during 

 the night, whined at intervals, coordination disturbed, appeared very sick, but 

 exhibited no other symptoms. 



December 21: 9 a. m., found dead, stiff, and cold. 



The total amount of caffein received by dog 24 was between 10.109 and 11.484 grams. 

 As one of the capsules vomited was intact and the other broken open, the amount was 

 probably about 10.75 grams. The fatal dose in this case was undoubtedly less than 

 185 mg per kilo somewhere between 125 and 185 mg. Autopsy showed heart in 

 diastole; posterior lobe of right lung deeply congested; liver engorged; gall cyst filled; 

 spleen appeared normal; stomach well filled with semifluid mass; pyloric portion of 

 stomach exhibited a severe inflammation of mucosa; mucosa of duodenum greatly 

 inflamed and showed hemorrhagic areas and catarrhal exudate; remainder of small 

 intestine also exhibited mild inflammation; kidneys deeply engorged, mesentery 

 injected. 



A comparison of the fatal doses of caffein in the experiments on high and low protein 

 diet does not show much difference in the resistance to caffein, since 175 mg per kilo 

 proved fatal to Nos. 30 and 32, while No. 29 died after receiving 150 mg per kilo, and 

 No. 24 received 125 to 185 mg per kilo. Moreover, No. 28, which was changed from 

 low to high protein diet, succumbed when given 125 mg per kilo. Observations made 

 during the experimental period indicate, however, greater toxicity of caffein in the 

 subjects on low protein diet. Dog 30 showed the effects of the drug when the 

 dose was increased to 125 mg of caffein per kilo, while in No. 32, 150 mg per kilo were 

 received without any manifestation of symptoms. Dog 31, which was likewise on a 

 high protein diet, is evidently an exception, and its low resistance to caffein may be 

 accounted for by the condition found at autopsy. In other dogs on low protein diet 

 symptoms of intoxication appeared early in the experiment. In Nos. 29 and 24 it 

 was observed as soon as the amount of caffein was increased to 75 mg per kilo. In 

 dog 28 the first dose of caffein 50 mg per kilo was toxic. The symptoms of gastro- 

 intestinal disturbance were especially marked after caffein on low protein diet. This 



