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 grams. 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: 3.29¼ to 3.37½ 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 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.