A significant difference exists in the sensitivity of rats and mice to the acute toxicity of MAN. Present investigations were undertaken to provide additional characterization of MAN metabolism and disposition and to study the metabolic basis for the species differences in its toxicity. Male F344 rats and B6C3F1 mice received a single gavage dose of 11.5 or 1.15 mg 14C-MAN/kg. Elimination of MAN-derived radioactivity in rats occurred primarily in urine and as CO2. Three major urinary metabolites of MAN were identified as N-acetyl-S-(2-cyanopropyl)-L- cysteine (NACPC), N-acetyl-S-(2-hydroxypropyl)-L-cysteine (NAHPC), and deoxyuridine. Quantitatively, rats and mice excreted ca. 7 and 49% of the high MAN dose in urine as NAHPC, respectively. This metabolite is thought to result from the degradation of the GSH/MAN epoxide intermediate. In addition, rats eliminated significantly more MAN- derived CO2 and deoxyuridine than mice. MAN elimination is almost complete in 24 hr after dosing and the tissue concentrations of MAN- derived radioactivity were, with the exception of the urinary bladder, consistently higher in rats than in mice.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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