Mutagenicity detection of in vivo nitrosation of dimethylamine by nitrite.
Whong-Z; Speciner-ND; Edwards-GS
Environ Mutagen 1979 Jul; 1(3):277-282
The in-vivo nitrosation of dimethylamine (124403) was measured in a host mediated mutagenicity assay. The nitrosated product, nitrosodimethylamine (62759) (NDMA), a known mutagen, was detected. Salmonella-typhimurium was administered intravenously to mice and rats 10 minutes prior to sequential gavage with dimethylamine and sodium-nitrate (7631994). Dimethylamine was given at 1.3 to 216 micromoles per kilogram body weight. Controls were given dimethylamine or sodium-nitrate alone or a citrate buffer. After 2 hours the livers were removed, homogenized and filtered. Dilutions were plated for determination of bacterial survival and histidine negative to histidine positive reversion frequency. A linear log dose/mutagenicity curve was obtained at doses between 2 and 50 micromoles for mice and 5 and 25 micromoles for rats. At higher doses the curves became non linear. The lowest doses of NDMA that could be detected by this system were 2.7 micromoles for mice, equivalent to 0.2 milligram per kilogram (mg/kg), and 8 micromoles for rats, equivalent to 0.6mg/kg. Neither dimethylamine nor sodium- nitrate alone exhibited detectable mutagenic activity. The authors conclude that this system makes possible the detection of formation of NDMA at concentrations much lower than previously reported. The nitrosation can be recognized from low concentrations of precursors.
NIOSH-Author; In-vivo-studies; Biochemical-analysis; Carcinogenicity; Laboratory-animals; Chemical-properties; Bioassays; Bacteriology; Dose-response; Mutagenesis
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