Abstract

The metabolism of alachlor was studied using in vitro incubations with microsomal fractions prepared from liver and nasal turbinates of rats and mice. Specifically, the transformation of alachlor to 3,5-diethylbenzoquinone-4-imine was examined. A key intermediate in this pathway was identified as 2,6-diethylaniline, the formation of which required catalysis by microsomal arylamidases. 2,6-Diethylaniline was oxidized to 4-amino-3,5-diethylphenol and the electrophilic 3,5-diethylbenzoquinone 4-imine. Rat nasal tissue possessed high enzymatic activity which can promote the formation of the reactive quinone imine. Whole body autoradiographic analysis demonstrated localization of radioactivity in the rat nasal tissue following oral administration of alachlor. A methylsulfide metabolite of alachlor was shown to be a precursor to 2,6-diethylaniline. The deposition of radioactivity in the rat nasal tissue was more pronounced following oral administration of the methylsulfide metabolite of alachlor.