Metabolism of N-nitrodialkylamines

The in-vitro and in-vivo metabolism of N-nitramines was investigated to compare it with that of N-nitrosamines. N-Nitrodibutylamine and N-nitrodiethylamine were incubated with rat liver microsomes and hepatocytes, and the products were analysed by high-performance liquid chromatography and gas-liquid chromatography. The in-vitro metabolic pattern of these N-nitramines was similar to that of the corresponding N-nitrosamines, except that N-nitromonoalkylamines (produced by alpha-hydroxylation) were isolated and identified after incubation of N-nitrodialkylamines. Seven N-nitramines, including glucuronides, were isolated and identified from urine of rats given N-nitrodibutylamine, produced by omega, omega-1, and alpha oxidations of the N-nitramine. The in-vivo metabolic pattern of N-nitrodibutylamine was also similar to that of N-nitrosodi-n-butylamine except that N-nitromonobutylamine (a product of alpha-hydroxylation) was isolated and identified. N-Nitramines were mutagenic to Escherichia coli WP2 hcr-, but not to Salmonella typhimurium TA 1535. N-Nitrodibutylamine and N-nitrodiethylamine were mutagenic only in the presence of hepatic microsomes, while N-nitromonobutylamine and N-nitromonoethylamine were direct mutagens. Thus, the N-nitrodialkylamine is also metabolically activated to a mutagen through an alpha-hydroxylation.