Sex-, age- and pregnancy-induced changes in the metabolism of toluene and trichloroethylene in rat liver in relation to the regulation of cytochrome P450IIE1 and P450IIC11 content.

Sex-, age- and pregnancy-induced changes in the metabolism of toluene and trichloroethylene in rat liver were investigated in relation to the regulation of cytochrome P450IIE1 and P450IIC11 content using monoclonal antibodies. Immature male rats had a higher level of microsomal protein than females, and this increased with development; however, no difference by sex was found at puberty. No difference in cytochrome P450 content was seen between immature male and female rats; the content increased with development only in males, so that a sex difference in cytochrome P450 content occurred at puberty. Pregnancy decreased the cytochrome P450 content but not that of the microsomal protein. The rate of formation of benzyl alcohol from toluene was 4 times higher in mature than in immature male rats at a high concentration of toluene, but no difference was seen at a low toluene concentration. In contrast, the rate was lower in mature female rats than in immature ones at a low toluene level and no difference was seen at the high concentration. A sex difference was thus found in benzyl alcohol formation at puberty at both concentrations of toluene. The levels of o- and p-cresol formation in liver were similar in males and females but the rate decreased during development of females. The rate of metabolism of trichloroethylene was higher in immature than in mature male and female rats, especially at a low substrate level, and no sex difference in metabolism was seen with either age or concentration of trichloroethylene. Pregnancy decreased the metabolism of both toluene and trichloroethylene.(ABSTRACT TRUNCATED AT 250 WORDS)