Mutagenicity studies of selected antihistamines, their metabolites and products of nitrosation.

Methapyrilene, four structurally related antihistamines, three metabolites of methapyrilene and two products of the reaction of methapyrilene with nitrite were all tested for mutagenicity to Salmonella typhimurium. The two products of the methapyrilene-nitrite reaction have also been identified as metabolites of methapyrilene. None was mutagenic alone, either with or without rat liver S-9 activation. After reaction with sodium nitrite in acetic acid solution (nitrosation), the products of five of the ten compounds were mutagenic. These compounds were methaphenilene, 2-thiophenemethanol, 2-thiophenecarboxylic acid, N-(2-pyridyl)-N'N'-dimethylethylenediamine and N-(2-thenylmethyl)-2-aminopyridine.