Carcinogenicity of Substituted-Benzenediamines (Phenylenediamines) in Rats and Mice2

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Abstract
The results of carcinogenicity studies of thirteen substituted-benzenediamines (SBD) were summarized and compared with the results of various relevant short-term tests. SBD studied were o-phenylenediamine·2HCl, m-phenylenediamine·2HCl, p-phenylenediamine·2HCl, 4-chloro-o-phenylenedi-amine, 4-chloro-m-phenylenediamine, 2-;chloro-p-phenylenediamine sulfate, 2-nitro-p-phenylenediamine, 4-nitro-o-phenylenediamine, 2,4-diaminotoluene, 2,5-diaminotoluene sulfate, 2,6-diaminotoluene·2HCl, 2,4-diaminoanisole sulfate, and 3-amino-4-ethoxyacetanilide. Eleven SBD were tested in the inbred F344 rat and (C57BL/6N♀ × C3H/HeN♂)F1 mouse and two SBD in the outbred Charles River CD stock rat and Charles River albino CD-1 stock mouse. o-Phenylenediamine, 4-chloro-o-phenylenedi-amine, 2,4-diaminotoluene, and 2,4-diaminoanisole induced statistically significant incidences of tumors in both rats and mice. 4-Chloro-m-phenylenediamine, 2-nitro-p-phenylenediamine, and S-amino-4-ethoxyacetanilide induced tumors only in mice. Tumor types induced by at least one of the carcinogenic SBD were found at an elevated, though not statistically significant, level in animals treated with one of the other five SBD. Detailed tumor incidence data on m-phenylenediamine were not available to determine if it also produced a treatment-related effect. The mouse, particularly the female, was more susceptible than the rat to the carcinogenic effects of the SBD. The rat, however, showed a greater range of target organ susceptibility. The SBD appeared to be least active when the amino groups were para to one another and gained activity as they became ortho to the substituted group. All the SBD studied in short-term tests were positive in at least one assay system.