Mutagenicity of amine drugs and their products of nitrosation.
8 drugs that are amines or amides and that interact with nitrous acid to form potentially carcinogenic and mutagenic N-nitroso derivatives were tested for mutagenicity to Salmonella typhimurium. None of the compounds was mutagenic alone, with or without liver S9 activation. After reaction with nitrite in acetic acid solution, the products of 4 of the compounds were mutagenic. Diphenhydramine and hydrochlorothiazide gave products mutagenic with or without activation, but only to strain TA98. Methaphenilene gave products mutagenic to TA1538, TA98 and TA100 without microsomal activation. Dimethyldodecylamine-N-oxide after nitrosation was mutagenic with S9 activation to TA1535 indicating a response to the nitrosomethyldodecylamine formed. Allantoin, pyrilamine, chlorothen, methafurylene and thenyldiamine were not mutagenic alone or after nitrosation.
D000588:Amines / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009602:Nitrosamines / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity; D013329:Structure-Activity Relationship
D000588:Amines; D009153:Mutagens; D009602:Nitrosamines