Part 33

July 17: 3 p. m., 17 cc of 2 per cent caffein (124 mg per kilo) given by mouth through stomach tube at 3.20 p. m.; 5 p. m., very irritable, but no other symptoms.

July 18: Under observation all day, no symptoms.

Cat 93. Black and white female. Weight, 1,640 grams.

July 17: 3.30 p. m., 10 cc (0.125 gram per kilo) of 2 per cent caffein given by mouth through stomach tube.

July 18: Under observation all day, no symptoms.

From the results of the experiments of this series it appears that 0.15 gram caffein per kilo may be fatal within a few hours after its administration, even if the drug is mixed with a moderate amount of meat. Experiments 87 and 92 show, however, that this amount may be borne by some individuals without any serious consequences, as the cats were under observation for some time after they received caffein, and no untoward symptoms were noticed in either of them during this time. It may be remarked that cat No. 92 vomited shortly after it received caffein. It is practically certain, therefore, that this amount of caffein in proportion to the weight of the animal will in the great majority of cases prove fatal, and perhaps in a smaller percentage of individuals it is surely toxic if it does not escape absorption. Smaller doses may cause irritability in some individuals, but symptoms referable to nervous symptoms of muscles were absent, as in experiments Nos. 93 and 100. The minimum fatal dose of caffein for the cat when given by mouth is, therefore, 0.15 gram per kilo.

TABLE 9.--Subcutaneous injection; cats.

SERIES A.

-------+--------+---------+-----------------------+------------------- Number.| Weight.| Caffein | Symptoms. | Duration of life. | |per kilo.| | -------+--------+---------+-----------------------+------------------- |Grams.| Gram. | | 4 | 1,440 | 0.30 | 65 minutes | Over 29 hours. 5 | 1,396 | .30 | | About 2 hours. -------+--------+---------+-----------------------+-------------------

SERIES B.

-------+--------+---------+-----------------------+------------------- 3 | 2,854 | 0.25 | | 30 minutes. 6 | 1,645 | .243 | Few minutes | 1 hour 30 minutes. 8 | 1,735 | .25 | 30 minutes. | 1 hour. 9 | 1,960 | .25 | 1 hour | 1 hour 45 minutes. 12 | 1,185 | .20 | 3 hours | Less than 18 hours. 14 | 1,855 | .20 | 1 hour 20 minutes | Do. 15 | 2,145 | .20 | 40 minutes. | Do. 19 | 1,100 | .236 | 15 minutes | Do. 20 | 790 | .25 | | 4 hours 30 minutes. -------+--------+---------+-----------------------+--------------------

SERIES C.

-------+--------+---------+-----------------------+------------------- 24 | 1,300 | 0.153 | 1 hour | Survived. 17 | 2,620 | .15 | 15 minutes | Do. 23 | 1,645 | .15 | | 1 hour 10 minutes. 7 | 1,285 | .155 | 20 minutes | 1 hour. 9 | 2,285 | .14 | | 65 minutes. -------+--------+---------+-----------------------+-------------------

SERIES D.

-------+--------+---------+-----------------------+------------------- Number.|Weight. | Caffein | Symptoms. | Duration of life. | |per kilo.| | -------+--------+---------+-----------------------+------------------- |Grams.| Gram. | | 13 | 730 | 0.139 | Restlessness | 21 | 1,165 | .138 | None | 25 | 965 | .103 | do. | 26 | 1,605 | .125 | do. | 27 | 1,625 | .125 | do. | 28 | 2,335 | .128 | do. | Received 2 doses: | | | | survived. 40 | 2,710 | .129 | do. | Do. 41 | 1,785 | .123 | do. | Do. 42 | 2,315 | .112 | do. | Do. 38 | 2,325 | .120 | Mild | Died after second | | | | dose. -------+--------+---------+-----------------------+-------------------

SERIES E.(1)

-------+--------+---------+-----------------------+------------------- 43 | 3,225 | 0.124 | | 40 minutes. 48 | 3,050 | .118 | | Died soon after. 47 | 4,220 | .084 | | Survived. (2)47 | 4,250 | .084 | | 2 hours. -------+--------+---------+-----------------------+-------------------

(1) Pathological conditions.

(2) Two days after first injection.

TABLE 10.--Injections into peritoneal cavity; cats.

-------+--------+---------+-----------------------+------------------- Number.|Weight. | Caffein | Symptoms. | Duration of life. | |per kilo.| | -------+--------+---------+-----------------------+------------------- |Grams.| Gram. | | 99 | 3,000 | 0.100 | Mild | Survived. 98 | 4,100 | .100 | do.(1) | Do. 93 | 1,450 | .137 | Very mild | Do. 87 | 2,615 | .145 | do. | Do. 97 | 505 | .200 | None | 5 days. 96 | 575 | .139 | do. | 6 days. 95 | 860 | .200 | 15 minutes | 30 minutes. 94 | 790 | .200 | Diarrhea | Survived. 10 | 2,970 | .200 | | 1 hour. 16 | 2,420 | .183 | | 30 minutes. -------+--------+---------+-----------------------+-------------------

(1) In few minutes.

TABLE 11.--Administration of caffein by mouth; cats.

-------+--------+---------+-----------------------+------------------- Number.|Weight. | Caffein | Symptoms. | Duration of life. | |per kilo.| | -------+--------+---------+-----------------------+------------------- |Grams.| Gram. | | 91 | 3,050 | 0.15 | 1 hour 40 minutes | 2 hours. 88 | 3,260 | .15 | | 1 hour 40 minutes. 92 | 1,750 | .16 | 25 minutes | Survived. 87 | 2,620 | .15 | 3 hours | Do. 90 | 2,685 | .20 | 1 hour 15 minutes | Less than 18 hours. 89 | 2,860 | .20 | | 75 minutes. 82 | 2,450 | .15 | | Less than 24 hours. 100 | 2,740 | .124 | 1 hour 40 minutes | Survived. 93 | 1,640 | .125 | | Do. -------+--------+---------+-----------------------+-------------------

SUMMARY.

The toxicity of caffein in cats is shown to be the same when given by mouth as when injected subcutaneously, the minimum fatal doses in both cases being 0.15 gram per kilo. When introduced by the intraperitoneal route, caffein is, on the contrary, distinctly less toxic. After the administration of 0.137 and 0.145 gram caffein per kilo (Nos. 93 and 87) salivation in one cat (No. 93) and irritability and muscular stiffness in the other were the only effects noticed. These symptoms were no longer observed the next day and the cats appeared to be perfectly normal. Experiments with larger doses indicate that the minimum fatal dose by this method of administration is about 0.2 gram per kilo.

EXPERIMENTS ON DOGS.

The experiments were carried out on well-fed adult dogs and on puppies, kept under observation for some time before the drug was administered. Only those manifesting no signs of abnormality were used for these tests. Caffein was given by mouth mixed with 10 to 20 grams of meat, or subcutaneously in 2 per cent aqueous solution. The young animals received caffein dissolved in milk. The determination of the minimum toxic or fatal doses when the drug was fed presented considerable difficulty, as in many instances the ingestion of the drug was closely followed by vomiting.