ACUTE INTOXICATION RABBITS. 39 



In the eight cxpcrimcnta comprising series B rabbits Nos. 567, 254, 279, and 255, 

 which may be designated as Group II, received doses of 162, 160, 166, and 158 mg, 

 respectively. Nos. 562, 561, 560, and 559, which may be designated as Group I, 

 received about 200 mg caffein per kilo. In Group II, which received the smaller 

 doses, one (No. 254) survived. This may be regarded as exceptional, since, as was 

 shown in the experiments of the preceding series, even smaller doses may be fatal. 

 About 160 mg per kilo is, therefore, the smallest surely fatal dose. This might be 

 regarded as a contradiction of the results obtained for rabbit No. 559, but it will be 

 noticed that in this case diuresis was very marked. The results of experiments 

 Nos. 294 and 255 are of interest in this connection, since they indicate that a moderate 

 difference in the rate of injection is without any effect on the toxicity of caffein. 

 The greater resistance to caffein of rabbit No. 559 is in all probability due, therefore, 

 to increased diuresis. 



SERIES C. 



In these experiments the minimum toxic dose was determined. The conditions 

 were the same as in the experiments of the other series. 



Rabbit 293. Belgian hare, female. Weight, 1,610 grains. Diet, oats. 



February 18: 3.40 to 3.43 p. m., 4 cc 2 per cent warm caffein solution injected into 

 ear vein, convulsions when 3 cc were injected, repeated attacks; 4 p. m., raised itself 

 on legs, but fell over immediately and lay stretched on abdomen. 



February 19: 9 a. m., rabbit looked normal, apparently recovered. 

 Rabbit 227. White male. Weight, 2,320 grams. 



October 26: 3.29 to 3.37 p. m., injected into ear from burette 6.7 cc 2 per cent 

 caffein, no symptoms; experiment discontinued; survived. 

 Rabbit 563. Gray female. Weight, 1,650 grams. Diet, oats. 



February 6: Injection began at 1.02 p. m., injected 3.5 cc 2 per cent caffein (42 mg 

 per kilo) in four minutes, 0.6 cc more within the next two and one-half minutes, total 

 amount injected 4.1 cc; 1.10 p. m., hypersensitive, some disturbance of muscular 

 coordination; restlessness; 1.35. p m., reflexes decreased, urinated and walked about, 

 gait normal. Under observation for several days; no symptoms noted. 

 Rabbit 564. Gray female. Weight, 1,515 grams. 



February 6: Injection began at 1.26 p. m., 3.5 cc 2 per cent caffein (46 mg per kilo) 

 injected at the rate of 1 cc per minute; 1.30 p. m., reflexes increased; 1.34 p. m., 

 marked paresis of the extremities, rabbit stretched out on abdomen, legs abducted 

 and partly extended, able to hop about but gait disturbed, no untoward symptoms 

 noticed, under observation for several days after experiment. 

 Rabbit 565. Gray female. Weight, 1,545 grams. Diet, oats. 



February 6: Started to inject at 3.40 p. m., received 2.5 cc 2 per cent caffein intra- 

 venously in two minutes or 32 mg per kilo, under observation all afternoon, no 

 symptoms. 



Rabbit 566. Gray female. Weight, 1,900 grams. Diet oats. 



February 6: Injection began at 3.05 p. m., received 3 cc 2 per cent caffein intra- 

 venously in three minutes or 31 mg per kilo, no symptoms observed. 



These experiments show that a dose of about 50 mg per kilo when injected intra- 

 venously produces mild symptoms, such as increased reflexes. In the four experi- 

 ments with this amount of caffein these effects were observed in each case. In the 

 experiments in which smaller quantities, 30 mg per kilo, were given intravenously 

 there was no manifestation of symptoms. A dose not over 50 mg per kilo may, there- 

 fore, be regarded as the minimum toxic dose when injected intravenously under the 

 conditions stated. 



SERIES D. 



A 0.5 per cent caffein solution was used in these experiments in order to test the 

 effect of concentration on its toxicity; the rate of injection was 1 cc per minute. 

 Rabbit 569. Gray male. Weight, 1,475 grams. Diet, oats. 



February 6: 11.50 a. m. to 12.01 p. m., injected 10 cc 0.5 per cent caffein; 12.03 

 to 12.12 p m., injected 10 ccof 0.5 per cent caffein; 12.13 to 12.26 p. m., injected 



