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 intravenously 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 intravenously 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 intravenously produces mild symptoms, such as increased reflexes. In the four experiments 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, therefore, 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.