Mutagenicity of 22 N-nitrosamides and related compounds for Salmonella typhimurium TA1535.
Twenty-two N-nitrosamides and related compounds, including 14 nitrosoureas, 5 nitrosocarbamates, and one nitrosocyanamide, were tested at various concentrations for mutagenic activity towards Salmonella typhimurium TA1535 without the use of microsomes. The ether-water partition coefficient, solubility in water, and half-life in aqueous solution were also measured. Twenty compounds were mutagenic, with "standard mutagenic concentrations" (i.e. those producing 100 mutants/dish) of 0.0024--6500 micron. Standard mutagenic concentration was negatively correlated with the partition coefficient. Three compounds (ethyl 2-acetoxyethylnitrosocarbamate, nitrosocarbaryl, and methylnitrosobenzamide) were more active than the classic mutagen methylnitrosonitroguanidine. Nitrosocarbamates were at least 50 times more mutagenic than the corresponding nitrosoureas. Nitrosodihydrouracil and propylene-nitrosourea were more active than related compounds. Ethylnitrosocyanamide was 730 times more mutagenic than ethylnitrosourea. Fifteen of the test compounds (of which 14 were mutagenic) had previously been assayed in rats for carcinogenicity, all with positive results.
D000577:Amides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D009153:Mutagens; D009602:Nitrosamines / Q000494:pharmacology*; D009603:Nitroso Compounds; D009607:Nitrosourea Compounds / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013696:Temperature
D000577:Amides; D009153:Mutagens; D009602:Nitrosamines; D009603:Nitroso Compounds; D009607:Nitrosourea Compounds; C013621:nitrosamides