Methoxychlor is considered as pro-estrogen, while some of its metabolites are more potent
endocrine disruptors than the parent insecticide. Major activation of methoxychlor is through
cytochrome P450-catalyzed demethylation to bisphenol A-like metabolites. Cunninghamella elegans
is a well-known fungal species with its strong resemblance of the xenobiotic metabolism of the
mammalian system. In this study, the metabolism of methoxychlor was investigated with the
corresponding organism. Methoxychlor was rapidly transformed to approximately 11 metabolites
in phase I metabolism, including oxidation, hydroxylation, and dechlorination. Concentrations of
phase I metabolites reached a maximum at 4-6 days and gradually decreased until the end of the
experiments. Most metabolites from the phase I reaction were further transformed to sugar
conjugates. Approximately 11 or more glucose conjugates were found in culture supernatants
and gradually increased, while no glucuronides were observed throughout the experiments.
Piperonyl butoxide and chlorpyrifos strongly inhibit the degradation of methoxychlor and concomitant
accumulation of metabolites, indicating cytochrome P450 mediated metabolism. Little or no glycosides
were detected in chlorpyrifos- and piperonyl butoxide-treated cultures. From the results,
Cunninghamella elegans has shown strong similarities of the phase I metabolism of methoxychlor,
while the conjugation reaction is different from those of animal metabolism.