Table 17.—Chronic intoxication of rabbits, series B, Group IV, on cumulation.

RABBIT, 370.
Date. Weight. Carrots. Water. Urine. Caffein by stomach. Symptoms.
Grams.Grams. cc. Mg per kilo.
Aug. 7 2,155 450 50 280
Aug. 8 2,030 450 25 185
Aug. 9 2,105 290 0 275
Aug. 10 2,095 450 30 335
Aug. 11 2,105 450 65 360 50
Aug. 12 2,125 450 65 220 50
Aug. 13 2,120 350 25 265 50
Aug. 14 2,170 450 35 275 75
Aug. 15 2,175 350 (?) 200 75
Aug. 16 2,170 360 65 250 75
Aug. 17 2,175 310 35 170 100
Aug. 18 2,095 180 40 285 100 Severe diarrhea.
Aug. 19 2,120 400 (?) 285 125 Do.
Aug. 20 2,120 400 (?) 310 125 Better.
Aug. 21 2,120 400 70 250 125 Do.
Aug. 22 2,040 400 45 265 150 Diarrhea bad.
Aug. 23 2,030 370 35 220 150 Diarrhea better.
Aug. 24 1,950 215 40 120 150 Do.
Aug. 25 1,885 195 35 60 200 Reflexes.
Aug. 26 Found dead at 9.
RABBIT, 373.
Aug. 7 2,240 450 50 230
Aug. 8 2,150 150 30 300
Aug. 9 2,120 205 0 150
Aug. 10 2,150 450 15 245
Aug. 11 2,195 450 5 285 50
Aug. 12 2,160 450 65 325 50
Aug. 13 2,120 300 45 190 50
Aug. 14 2,195 450 40 265 75
Aug. 15 2,215 350 35 200 75
Aug. 16 2,205 310 45 225 75
Aug. 17 2,240 400 40 265 100
Aug. 18 2,255 350 30 320 100
Aug. 19 2,115 185 (?) 170 125 Severe diarrhea.
Aug. 20 2,115 280 35 195 125 Diarrhea better.
Aug. 21 2,050 175 75 115 125 Slight diarrhea.
Aug. 22 2,060 180 75 130 150
Aug. 23 2,005 200 75 125 150 Reflexes.
Aug. 24 1,990 200 75 150 150 Slight diarrhea.
Aug. 25 1,950 255 55 132 175 Severe diarrhea.
Aug. 26 1,870 205 80 140 None Do.
Aug. 27 1,830 200 50 140 do. Do.
Aug. 28 1,950 400 25 265 do. Slight diarrhea.
Aug. 29 1,825 400 0 315 do. Very weak and in poor condition
Aug. 30 1,850 10 140 do.
Aug. 31 1,835
RABBIT, 370.
Aug. 7 2,240 450 50 300
Aug. 8 2,260 450 50 225
Aug. 9 2,310 430 (?) 300
Aug. 10 2,295 450 50 305
Aug. 11 2,320 450 50 335 50
Aug. 12 2,280 450 70 400 50
Aug. 13 2,300 350 70 255 50
Aug. 14 2,265 425 55 154 75
Aug. 15 2,260 250 40 125 75
Aug. 16 2,295 155 70 Lost 75
Aug. 17 2,180 105 70 120 100Severe diarrhea.
Aug. 18 2,150 125 70 100 100Diarrhea better.
Aug. 19 2,075 210 (?) 192 100Diarrhea severe.
Aug. 20 2,075 280 70 180 100 Do.
Aug. 21 2,165 260 50 225 NoneDiarrhea better.
Aug. 22 2,105 400 50 275 do.
Aug. 23 2,080 300 0 145 do.Diarrhea severe.
Aug. 24 2,105 250 15 245 do. Do.
Aug. 25 2,055 320 10 176 150Reflexes.
Aug. 26 2,040 190 75 250 150Died at 1 p. m., without having showed any symptoms other than reflexes.

Series C.

The subjects used in these experiments were rabbits of medium size and were apparently young or at any rate were not very old. The series was planned for the study of the possible effect of diet on the toxicity of caffein when given for some time, and therefore oats were substituted for carrots, which had been fed in the previous work, as already stated. Caffein was given by mouth in the usual way, in 1 per cent solution, 100 mg. per kilo daily. Fourteen rabbits were used for these tests. Their weights were recorded daily and observations made at frequent intervals during the day.

The only change noticed in all of the experiments of this series was progressive loss of weight which set in from 3 to 8 days after the administration of the drug was begun. The duration of life varied considerably. No. 382 died after the first dose. No. 389 lived 2 days, No. 386, 3 days, and No. 385, 5 days; No. 390 lived 7 days and No. 404 lived 20 days after the administration of caffein was begun. The duration of life in all the others was from 11 to 16 days. The findings at autopsy are interesting and suggestive as regards the possible explanation of the effects of repeated dosage of caffein. In eight of the rabbits there was involvement of the mucous membrane of the stomach or intestines or of both. Since the same condition of the gastro-intestinal canal was observed in previous experiments with caffein when injected subcutaneously, the mere passing of the tube into the stomach is obviously not the cause of this condition. The fatal outcome due is therefore, as was suggested above, to inanition brought about by the condition of the gastro-intestinal canal. Moreover parallel experiments carried out on rabbits in the same way with alcohol survived this treatment much longer. Obviously then the passing of the soft rubber catheter is not the cause of this condition of the gastro-intestinal canal nor the diet. Rabbits were fed oats exclusively for several months in this laboratory and thrived. The presence of pneumonia in the other rabbits of this series may be regarded as accidental, as it is inconceivable that one or two doses of caffein, as was the case in Nos. 382 and 389, could predispose the lungs to infection. The results of these experiments therefore are in harmony with those of the preceding two series, indicating that caffein does not accumulate in the body, and that the toxicity of caffein, whether of the single dose or of repeated doses is the same, on a diet of carrots or of oats. These results also show that caffein is much more toxic with repeated dosage. As stated in the historical part of this bulletin the same view was held by Gourewitch.[28]

Rabbit 386. Belgian female.

Given 1 cc of 1 per cent caffein for each 100 grams, through stomach tube.

Date. Weight. Treatment. Date. Weight. Treatment.
Grams. cc. Grams. cc.
Aug. 17 1,300 13.0 Aug. 19 (?) (?)
Aug. 18 1,215 12.0