Doses of 160 to 200 mg caffein per kilo were employed in these
experiments. The rate of injection was 1 cc per minute, with the
exception of Experiment 254, in which 10.8 cc 2 per cent caffein were
introduced in 17 minutes and 25 seconds.
_Rabbit 562. Gray female. Weight, 1,650 grams. Diet, oats._
February 1: Injection began at 3 p. m., injected 10 cc in 12 minutes;
3.01 p. m. to 3.09 p. m., 3 cc injected, convulsions; 3.09 p. m. to
3.14 p. m., 3 cc injected, followed by violent convulsions, marked
opisthotonos; 4.30 p. m., rabbit died; total quantity injected, 16 cc.
_Rabbit 561. Gray female. Weight, 1,450 grams. Diet, oats._
February 1: Injection began at 11.40 a. m.; 11.48, rabbit struggled,
7 cc 2 per cent caffein injected; 11.50, convulsions, 10 cc 2 per
cent caffein total amount injected; 11.55 a. m., injections stopped;
injections resumed 11.58, violent convulsions, injections discontinued,
total quantity received, 14.5 cc 2 per cent caffein solution;
1.30 p. m., found dead, did not urinate, 25 cc urine found in the
bladder.
_Rabbit 560. Gray male. Weight, 1,620 grams. Diet, oats._
February 1: Injection began 11 a. m.; 11.10 a. m., 7 cc 2 per cent
caffein injected, rabbit struggled; 1 cc was injected during the
next three minutes, rabbit struggled but there were no convulsions,
injection stopped; resumed at 11.15 a. m. and continued 10 minutes,
8 cc 2 per cent caffein introduced during this time; total amount
caffein injected, 16 cc; reflexes markedly increased; 12 noon, tetanic
convulsions off and on until 2 p. m., then remained stretched out on
abdomen, extremities extended.
February 2: 9 a. m., found dead.
_Rabbit 559. Gray female. Weight, 1,875 grams. Diet, oats._
January 31: 4 p. m., convulsions after injection of 9 cc 2 per cent
caffein in 14 minutes; 4.08 p. m., convulsions after injection of 7 cc
caffein in 8 minutes; 4.10 to 4.12 p. m., injected 2 cc more, rabbit
lying stretched out on abdomen, extremities extended; total amount of
caffein injected, 18 cc (190 mg per kilo).
February 1: 2 p. m., condition good, walked about, appetite good,
passed 155 cc dark, reddish-brown urine since 5.30 p. m. previous day.
_Rabbit 279. Gray and white female. Weight, 1,320 grams._
February 24: 10.09 a. m., 6 cc 2 per cent caffein passed rapidly
into jugular vein; 10.15 a. m., involuntary twitching of muscles
of legs, but no other symptoms; 10.23 to 10.26, 3 cc of 2 per cent
caffein injected; 10.27 to 10.28, 2 cc 2 per cent caffein injected,
convulsions; 10.29, convulsions stopped; 10.32, convulsions; 11 a. m.,
rabbit lying on its side, anterior extremities paralyzed, posterior
extremities contracted, no clonic convulsions, breathed deeper and
more slowly than normal; 11.10 a. m., rabbit died, had no convulsions
immediately before death; amount of caffein injected, 11 cc 2 per cent
solution, or 0.166 gram per kilo.
_Rabbit 254. Belgian hare, female. Weight, 1,285 grams. Diet, oats._
November 12: 1.30-1/3 to 1.47¾ p. m., received 10.8 cc 2 per
cent caffein from burette into ear vein, after injection of 6.2 cc
dyspnoea, 6.7 cc struggling, convulsions; at 1.50½ p. m., released
from holder, paralysis especially marked in the anterior extremities;
1.50 p. m., recovered, survived; total amount injected, 10.8 cc 2 per
cent caffein in 17 minutes and 25 seconds, or 0.16 gram caffein per
kilo.
_Rabbit 255. Belgian hare, male. Weight, 1,105 grams. Diet, oats._
November 12: 2.31¾ to 2.35¼ p. m., received 3.7 cc; from 2.37-1/6
to 2.46-1/6 p. m., 5 cc injected; after injection of 6.1 cc convulsions
followed by dyspnoea, then continuous struggling; when 8.3 cc were
injected rabbit had another convulsion; 2.47 p. m., tonic contraction
of anterior extremities; amount injected, 8.7 cc (158 mg per kilo) in
15 minutes and 35 seconds.
_Rabbit 567. Gray female. Diet, oats._
February 6: Injection began at 4.11 p. m.; 4.18, convulsions after
injection of 5 cc 2 per cent caffein; 4.21, convulsion after total
injection of 8 cc; 4.24 p. m., injection resumed and 2 cc more
introduced; 4.28 p. m., convulsions, injected 2 cc more; total caffein
injected, 12 cc, or 162 mg per kilo; 4.40 p. m., rabbit paralyzed in
posterior extremities; 5 p. m., found dead.
In the eight experiments 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.