MOCA and some proposed substitutes (Cyanacure, Conacure, Polacure 740M and Ethacure 300) as two-stage skin carcinogens in HRA/Skh hairless mice.

4,4'-Methylenebis(2-chlororaniline) (MOCA) is a suspect human carcinogen that has wide use as an industrial compound. Occupationally, exposure may occur through inhalation and ingestion, but skin absorption is the main route by which this compound gains entry into the body. Because of the justified concern about the continued use of MOCA, a number of substitutes have been proposed, including 1,2-bis(2-aminophenylthio)ethane (Cyanacure), Conacure, trimethylene glycol di-p-aminobenzoate (Polacure 740M) and 3,5-dimethylthio-2,4-toluenediamine/3,5-dimethylthio-2,6-tol uenediamine (Ethacure 300). There is very little information available about these substances, but they share the property of belonging to the same class (aromatic amines) as MOCA. Furthermore, at least two (Ethacure 300 and Cyanacure) are mutagenic in Salmonella. This study was undertaken to investigate if MOCA and substitutes, Polacure 740M, Ethacure 300, Cyanacure and Conacure have the potential to cause papillomas in a two stage initiation/promotion protocol in HRA/Skh hairless mice. When a maximum dose of 100 mg of substance was applied to the dorsal skin of these mice, Ethacure 300 and Cyanacure were markedly toxic. All of the compounds had little or no effect on skin tumor initiating activity following 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. One experiment with MOCA suggested that, at lower and less toxic dose, this substance may have promotional activity. Therefore, caution should still be exercised when using these compounds and it cannot be excluded that they may be active in other strains of mice or other laboratory animal species.