Age- and sex-related changes in toluene metabolism by rat hepatic microsomes in vitro

Age- and sex-related changes in toluene metabolism by hepatic microsomes of male and female Sprague-Dawley (SD) rats (1 to 20 weeks) were investigated . A major metabolite of toluene, benzyl alcohol (BA), was measured by high- performance liquid chromatography (HPLC). At low substrate toluene concentr ations (0.4 mM), in male rats, BA increased dramatically with development, reaching a peak at 5 weeks of age, rapidly decreasing thereafter. In female rats, BA increased dramatically with development at 3 to 5 weeks of age, a nd then declined gradually to a low level. Gender differences were obtained at 5 and 20 weeks of age, with BA products being higher in males than in f emales. At high substrate toluene concentrations (5.0 mM), in male rats, th e BA formation pattern was similar to that at the low substrate concentrati on, although the rate of increase with age was slower. In female rats, a pe ak was obtained at 3 weeks of age, and then declined gradually to a low lev el. Gender differences were obtained at 5, 15 and 20 weeks of age, with BA products being higher in males than in females. These results indicate that toluene metabolism exhibits age and gender differences.