October 5: 11.20 a. m., 4 cc of 2 per cent caffein (235 mg per kilo) injected into peritoneal cavity.
October 14: Alive and in good condition.
Guinea pig 64. Brown and black female. Weight, 305 grams.
October 5: 11.35 a. m., 3.8 cc 2 per cent solution caffein (250 mg per kilo) injected into peritoneal cavity; 11.40 a. m., tetanus—survived, convulsions off and on, died at 4.15 p. m. Autopsy: Findings exactly the same as in No. 67.
Examination of the results of the experiments by intraperitoneal injections showed that 0.2 gram caffein per kilo was toxic in two guinea pigs (Nos. 59 and 58). Severe symptoms were observed within 15 minutes in No. 56 and within one hour in No. 55 after the administration of approximately the same dose of caffein. One of these died within three and one-half hours; the other, No. 56, made a good recovery from the acute effects. This amount of caffein may be regarded, therefore, as the minimum toxic dose for the guinea pig when injected into the peritoneal cavity. This is corroborated by the experiments of series B in which smaller doses failed to show any muscular, nervous, or respiratory symptoms, nor were there any after effects noticed, as all of them survived and were kept under observation for some time. The guinea pigs of series A, however, seem to contradict these results. It will be remarked that appreciably smaller doses induced symptoms in all of them, and one case terminated fatally. The seasonal variation, as already pointed out, is in all probability likewise responsible for the difference in the resistance between the guinea pigs of series A and B. Tests were made also to determine the minimum fatal dose. For this purpose the experiments of series D were performed. The resistance of No. 63 in this series is quite striking. We are unable to explain such a discrepancy in the results obtained under practically uniform conditions. The minimum fatal dose of caffein, when injected into the peritoneal cavity, is therefore about 240 to 250 milligrams per kilo. These amounts, it will be observed, were rapidly fatal, in striking contrast to the results obtained when such doses were injected subcutaneously. This is probably due to a better absorption from the peritoneal cavity than from the subcutaneous tissues.
ADMINISTRATION BY MOUTH.
All the guinea pigs in these experiments were kept on a diet of hay and oats and were of large size. The tests were made with different doses of caffein in order to determine the limits of toxicity when the drug was administered by mouth.
Guinea pig 129. White and black male. Weight, 855 grams. Diet, oats and hay.
June 6: 2.20 p. m., 12 cc of 2 per cent caffein (0.28 gram per kilo) by mouth; 3 p. m., reflexes increased; 5 p. m., reflexes still more increased; no other symptoms.
June 7: 9 a. m., found dead; guinea pig passed 75 cc urine, which was almost colorless. Autopsy: Heart and blood vessels injected; lungs congested; small intestines congested; other organs apparently normal.