Metabolism in rats and mice of the soil fumigants metham, methyl isothiocyanate, and dazomet

Isotopic labeling of metham, methyl isothiocyanate (MITC), and dazomet with 13CH3 and 14CH3 and of metham and MITC With 13C = S provided the materials for metabolite identification by 13C NMR and quantitation by HPLC analysis and radiocarbon counting. Rats and mice were treated intraperitoneally and the metabolites studied at 48 h. Most of the 14CH3 label for each compound in mice appears in urine (58-80%) or is retained in the body (8-12%), particularly the liver and kidney. The major metabolites in each case from rats are S-(N-methylthiocarbamoyl)glutathione in the bile and S-(N-methylthiocarbamoyl)mercapturic acid in the urine, whereas from mice the mercapturate is a minor metabolite. Methylamine is a major urinary component following treatment with methylamine or dazomet (rats and mice) or metham (mice) but not with MITC. Detoxification by conjugation with glutathione (GSH) appears to involve direct reaction for MITC, GSH S-transferase-catalyzed reaction for metham, and the intermediacy of either MITC or metham for dazomet