Abstract
The in vitro metabolism of methoxychlor (MXC) and its mono-demethylated metabolites (mono-OH-MXC, including (R)- and (S)-enantiomers), was investigated using liver microsomes from rats and mice to rationalize the sex-dependent difference of MXC metabolism in rats. Kinetic analyses based on Eadie–Hofstee plots suggested that multiple enzymes were involved in MXC O-demethylation, whereas O-demethylation of mono-OH-MXC followed a standard one-enzyme model in all animal species studied. The kinetic parameters (Vmax, Km) indicated that enhanced enzymatic efficiency (CLint) in male rats was the cause of the sex-dependent metabolism of MXC in rats, while no such marked sex difference was observed in mice. It further appeared that female rats showed great enantioselectivity in O-demethylation that seemed to also be responsible for the sex-dependent metabolism. © Pesticide Science Sociey of Japan
