ROUTE OF ADMINISTRATION OF DRUGS IN RELATION TO TOXICITY IN CHEMOTHERAPEUTIC INVESTIGATIONS WITH SPECIAL REFERENCE TO INTRAPLEURAL INJECTIONS OF ETHYLHYDROCUPREIN HYDROCHLORID

¹ From the Dermatological Research Laboratories of Philadelphia

1. Ethylhydrocuprein hydrochlorid, other quinin compounds, mercurophen, arsphenamin and neoarsphenamin were 0.6 to 0.7 times more toxic for white rats by intrapleural than by intravenous injection.

2. Ethythyldrocuprein hydrochlorid and mercurophen were about 7 to 8 times more toxic for rabbits by subthecal injection than for white rats by intravenous injection.

3. Ethylhydrocuprein hydrochlorid, other quinin compounds and mercurophen were 3 to 4 times less toxic for white rats by intraperitoneal injection than by intravenous injection; arsphenamin and neoarsphenamin were 1 to 2 times less toxic.

4. Ethylhydrocuprein hydrochlorid, and other quinin compounds and mercurophen were 10 to 16 times less toxic for white rats by subcutaneous injection than by intravenous injection; arsphenamin was 2 times less toxic but neoarsphenamin was 0.5 to 1 times more toxic.

5. The toxicity of ethylhydrocuprein hydrochlorid by intravenous injection to mice, rats, guinea-pigs and rabbits was quite uniform the highest tolerated doses being 0.03 to 0.04 gram per kilogram of weight. Toxicity by subcutaneous injection varied from 0.500 gram per kilogram in the guinea-pig to 0.600 gram per kilogram in the mouse and rabbit.

6. The toxicity of arsphenamin and neoarsphenamin by intravenous and subcutaneous injection varies with the test animal, the highest tolerated doses being observed with mice, next with rats and rabbits in the order named.

7. There is no constant or uniform relation among the highest tolerated doses of different compounds for animals of the same species with the same route of administration. In very general terms a compound is apt to be about 8 times more toxic by subthecal than by intravenous injection; 0.6 to 0.7 times more toxic by intrapleural, 1 to 4 times less toxic by intraperitoneal and 2 to 16 times less toxic by subcutaneous, than by intravenous injection.

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