September 26: 2 p. m., 18 cc 2 per cent caffein administered by mouth; 4 p. m., reflexes increased, no tetanus; 6 p. m., condition unchanged since 4 p. m.
September 27: 9 a. m., found dead. Autopsy: Lungs, liver, and kidneys congested; other organs normal.
Rabbit 422. White, male. Weight, 1,440 grams. Diet, oats.
September 26: 2 p. m., 21 cc 2 per cent caffein (291 mg per kilo) given by mouth; reflexes increased at 4 p. m.
September 27: 3 p. m., alive, no symptoms; 4 p. m., convulsions with recovery, this was soon followed by a violent attack of tetanus, which lasted about one minute and was succeeded by paralysis; rabbit died at 4.30. Autopsy: Liver slightly congested; a small portion of the intestine showed congestion and edema; other organs normal.
A study of these experiments shows also considerable variation in the toxicity of caffein when given by mouth. In some cases a dose of 300 mg per kilo, and even less, caused death, as in rabbits 423 and 424. In other rabbits, however, approximately the same doses of caffein produced increased reflexes only. The same symptoms were produced in Nos. 248 and 249 after the administration of 325-330 mg of caffein per kilo, while another rabbit (No. 239) survived a dose of 363 mg per kilo. That this is exceptional, however, appears from the result of the following experiments on rabbits Nos. 419, 420, and 421, all of which died after receiving 350 mg of caffein per kilo, and rabbits 267 and 268, to which doses of 363 and 342 mg, respectively, per kilo proved fatal. It will be observed further that the gray rabbits are more resistant to caffein than the white animals, as 350 mg per kilo was the smallest fatal dose for rabbits 419, 420, and 421, all of which were gray rabbits, while a dose of 290 mg per kilo was fatal for some of the white rabbits. Again, it will be noticed that of the two gray rabbits, Nos. 254 and 239, which received the largest doses in these experiments, namely, 369 and 363 mg, respectively, one survived. The largest doses given to the white rabbits were 363 and 342 mg caffein per kilo. Both of these died from the effects of the drug. It may be concluded, therefore, that the minimum toxic dose for the gray rabbit is about 325 mg of caffein per kilo, and the minimum fatal dose is at least 350 mg per kilo. It is to be remarked in this connection that post-mortem examination showed extensive coccidiosis in rabbit 420 and fatty liver in No. 421, while the macroscopical examination of the organs of Nos. 424 and 423 failed to show the presence of such abnormalities. Since, as was observed in the section on subcutaneous injection and elsewhere in this investigation, pathological changes are apt to decrease the resistance to caffein, it is quite possible that 350 mg per kilo is not the minimum fatal dose for the normal rabbit. Indeed, the experiment on rabbit 239 lends support to this view, thus furnishing additional evidence of difference in the resistance to caffein in the two varieties of rabbits.
Table 2.—Administration of caffein by mouth.
| SERIES A. | ||||||
|---|---|---|---|---|---|---|
| Rabbit No. | Weight. | Caffein per kilo | Symptoms. | Duration of life. | Diet. | Remarks. |
| Grams. | Mg. | |||||
| 248 | 1,170 | 330 | 3 hours | Survived | Oats | Gray. |
| 241 | 1,380 | 290 | 2 hours | do. | do. | White male. |
| 249 | 890 | 325 | 3 hours | do. | do. | Gray male. |
| SERIES B. | ||||||
| 239 | 935 | 363 | Survived | Oats | Gray male. | |
| 254 | 975 | 369 | About 2 days | do. | Gray female. | |
| 267 | 1,050 | 342 | 50 minutes | 1 hour | do. | White. |
| 268 | 1,100 | 363 | About 3 hours | do. | Do. | |
| 419 | 1,600 | 350 | 6 hours | Less than | do. | Gray male. |
| 420 | 1,250 | 352 | 1 hour | 2 hours | do. | Do. |
| 421 | 1,485 | 351 | 6 hours | Less than | do. | Do. |
| 424 | 1,295 | 293 | 2 hours | 22 hours | do. | White male. |
| 423 | 1,205 | 300 | do. | Less than | do. | Do. |
| 422 | 1,440 | 291 | do. | 2½ hours | do. | Do. |