Comparative developmental dermal toxicity and mutagenicity of carbazole and benzo[a]carbazole

The objectives of this study were (1) to determine the developmental toxicity of carbazole and benzo[a]carbazole following daily dermal administration to female Sprague‐Dawley rats on days 0 through 20 of gestation and (2) to determine the mutagenicity of these two compounds using a modified version of the Ames assay. These chemicals are of concern because they are found in a variety of environmental matrices including crude oil mixtures. No signs of maternal or developmental toxicity were considered to be related to dermal administration of carbazole at doses of 2.5, 25.0, and 250.0 mg/kg. Signs of maternal toxicity considered to be related to administration of benzo[a]carbazole included significantly decreased body‐weight gain and decreased absolute‐food consumption at a dose of 250.0 mg/kg. Signs of developmental toxicity considered to be related to administration of benzo[a]carbazole included significantly decreased number of total (live and dead combined) and live pups on lactation day 0 as well as significantly decreased average pup weight on lactation days 0 and 4 at a dose of 250.0 mg/kg. Because developmental toxicity following benzo[a]carbazole treatment was observed only at a dose at which maternal toxicity was observed, it is likely that the effects on the offspring are secondary to the treatment effects on the dam. Evidence of toxic effects with benzo[a]carbazole in the absence of effects with carbazole suggests that the substituted benzene ring enhances the biological activity of this compound. Carbazole was nonmutagenic with or without S‐9 activation, whereas benzo[a]carbazole showed a clear dose–response with S‐9 activation. Without S‐9 activation, benzo[a]carbazole was nonmutagenic. Apparently benzo[a]carbazole must be enzymatically activated in order to be mutagenic.