Fluoro-substituted N-nitrosamines. 1. Inactivity of N-nitrosobis(2,2,2-trifluoroethyl)amine in carcinogenicity and...

N-Nitroso-bis(2,2,2-trifluoroethyl)amine (hexafluorodiethylnitrosamine, 6-F-DEN) was synthesized as a derivative of diethylnitrosamine (DEN) with blocked terminal C-atoms to avoid metabolic oxidation at this site. Chronic oral administration of 6-F-DEN in drinking water did not induce tumours in Sprague-Dawley and in Fischer 344 rats. On the other hand, equimolar doses of DEN or even much lower ones are clearly carcinogenic. Mutagenicity tests using Salmonella typhimurium strains TA 1535 and TA 100 and metabolic activation by rat liver S-9 fraction were equally negative with 6-F-DEn. The substitution of fluorine in the beta-position of DEn apparently inhibits the alpha-oxidation considered necessary for carcinogenesis and mutagenesis of dialkylnitrosamines.