Part 4

From a study of the literature on the toxicity of caffein it seemed that about 150 mg per kilo is probably the lethal dose for the rabbit when the drug is injected subcutaneously. Preliminary observations were therefore carried out with such a dose, but it was found, on the contrary, that this amount per kilo was hardly sufficient to induce symptoms in the great majority of cases.

SERIES A.

Rabbit 332. Belgian hare, female. Weight, 1,070 grams. Diet, oats.

March 25: 8.5 cc 2 per cent caffein (158 mg per kilo) injected subcutaneously at 2.15 p. m.; 4 p. m., reflexes increased; 5.45 p. m., increases of reflexes still more marked.

March 26: Rabbit looked normal; no symptoms observed.

Rabbit 331. Belgian hare, female. Weight, 1,170 grams. Diet, oats.

March 25: 2.15 p. m., 9 cc 2 per cent caffein (153 mg per kilo) injected subcutaneously; 4 p. m., reflexes increased; 5.45 p. m., condition the same.

March 26: Rabbit looks normal; no symptoms observed.

Rabbit 328. Belgian hare, female. Weight, 1,200 grams. Diet, oats.

March 25: 9 cc 2 per cent caffein injected subcutaneously (150 mg per kilo); 4 p. m., reflexes increased; 5.45 p. m., reflexes increased but not markedly.

March 26: No symptoms; rabbit looks normal.

Rabbit 322. White female. Weight, 1,065 grams. Diet, oats.

March 17: 8 cc 2 per cent caffein (150 mg per kilo) injected subcutaneously at 11.55 a. m.; 12.55 p. m., reflexes increased, but no tetanus nor any other symptoms.

March 18: Rabbit running around in cage; condition apparently normal.

March 25: Condition of rabbit good.

Rabbit 217. White. Weight, 1,355 grams. Diet, oats.

October 29: 10 cc 2 per cent caffein (147 mg per kilo) injected subcutaneously at 1.51 p. m. 5.15 p. m., rabbit alive; survived.

Rabbit 219. Maltese. Weight, 1,820 grams. Diet, oats.

October 29: 14 cc 2 per cent caffein injected subcutaneously at 1.40 p. m. (153 mg per kilo); 5.15, rabbit alive; survived.

Rabbit 194. White female. Weight, 1,490 grams. Diet, oats.

October 14: 13 cc 2 per cent caffein (174 mg per kilo) injected subcutaneously; increased reflexes and tremors were observed.

October 15: Condition of rabbit good; no symptoms.

Rabbit 191. Brown male. Weight, 1,915 grams. Diet, oats.

October 14: 16 cc 2 per cent caffein (167 mg per kilo) injected subcutaneously; reflexes increased and tremors present.

October 15: Condition of rabbit good.

A study of this series shows that about 150 mg of caffein per kilo caused increased reflexes within one to two hours after injection. When the dose was increased, as in rabbits 194 and 191, the symptoms were more pronounced; 150 mg per kilo may be regarded as the minimum dose which produces symptoms of nervous irritability when caffein is injected subcutaneously. Experiments with larger doses were therefore carried out in order to determine the minimum fatal dose.

SERIES B.

Approximately 0.2 gram of caffein per kilo was employed in these experiments. Diet and race as possible factors which may influence the toxicity of caffein were made the subject of study in these experiments which were divided into two groups as shown in the table, page 25.