Tests for Chemical Carcinogens. Report on the Activity of Derivatives of Aromatic Amines, Nitrosamines, Quinolines, Nitroalkanes, Amides, Epoxides, Aziridines, and Purine Antimetabolites23

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Abstract
In attempts to improve test systems to detect carcinogenic activity in chemicals, an experimental standard protocol applicable to a large number and variety of chemical structures was devised. Administration by gavage of compounds at several dose levels to male and female rats was performed 5 times per week for a total of 260 individual doses in 1 year. Reversible toxic lesions were assessed by sampling small groups of animals at that time. The remainder of the animals was observed an additional 6 months, unless earlier autopsy was required by the condition of the rats. In this system, 38 compounds of diverse structure, derivatives, or analogs of aromatic amines, quinolines, nitrosamines, alkylating agents, purine antimetabolites, and certain aliphatic amines or amides were examined. Ten compounds which were definitely carcinogenic included N,N′-dinitroso-N,N′-diethylethylenediamine, N,N′-dinitroso-N,N′-dimethyl-1,3-propanediamine, 1,4-dinitrosopiperazine, 3-methyl-2-naphthylamine, 3-nitro-2-naphthylamine, 4-(p-dimethylaminostyryl)quinoline, 2-(4-di-methylaminostyryl)benzothiazole, 3,3′-dimethoxybenzidine, N,4-dinitroso-N-methylaniline, and aphoxide. With 11 other compounds solitary tumors of a type (hepatoma, or papilloma of the lip or tongue) not seen in the controls were noted, indicating the need for further examination of these materials. The value of this test system is discussed, and on the basis of the experience achieved, certain modifications of the protocols are recommended.

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