The carcinogenicity of compounds related to 2-acetylaminofluorene. III. Aminobiphenyl and benzidine derivatives.

1. The carcinogenic activities for the rat of 4-acetylaminobiphenyl, N,N′-diacetylbenzidine, and eighteen related compounds have been investigated. The compounds were administered orally for 8–10 months. 2. Under these conditions 4-acetylaminobiphenyl induced a high incidence of adenocarcinomas of the mammary gland in female rats and small numbers of adenocarcinomas of the small intestine and squamous-cell carcinomas and sebaceous gland carcinomas of the ear duct. In addition to these tumors, 4′-fluoro-4-acetylaminobiphenyl induced a high incidence of liver tumors in male rats at 10–12 months. 3. 3-Hydroxy-4-aminobiphenyl and its N-acetyl derivative were noncarcinogenic. These compounds do not appear to be the effective carcinogen when 4-aminobiphenyl or its N-acetyl derivative is administered. 4. The following compounds had little or no carcinogenic activity under our conditions: 2-methyl-, 2′-methyl-, 2′-fluoro-, and 3-amino-4-acetylaminobiphenyl; 3-amino-4-dimethylaminobiphenyl; 2- and 3-acetylaminobiphenyl; 4-fluorobiphenyl; 4-acetylamino- p -terphenyl; acetanilide; and 3,4-dimethylacetanilide. 5. Rats fed N,N′-diacetylbenzidine developed a fatal glomerulonephritis which prevented adequate tests for carcinogenic activity. 2-Methyl-N,N′-diacetylbenzidine had moderate carcinogenic activity similar to that of 4-acetylaminobiphenyl; 3,3′-dimethyl-N,N′-diacetylbenzidine had weak activity; and 2,2′-dimethyl-N,N′-diacetylbenzidine was inactive. 6. The syntheses of the following new compounds are described: 3-hydroxy-4-aminobiphenyl, 3-hydroxy-4-acetylaminobiphenyl, and 2′-fluoro-4-acetylaminobiphenyl.