Metabolism of n-hexane by rat liver and extrahepatic tissues and the effect of cytochrome P-450 inducers.

1. The in vitro metabolism of n-hexane was studied in rat liver, lung, brain and skeletal muscle microsomes and in microsomes prepared from cell lines expressing human cytochrome P-450 2E1 or 2B6. The hydroxylated metabolites of n-hexane were quantified by gas chromatography-mass spectometry. 2. Rat liver and extensor digitorum longus (EDL, fast-twitch skeletal muscle) microsomes and the CYP 2B6 microsomes produced the pre-neurotoxic metabolite of n-hexane, 2-hexanol as a major metabolite in contrast to the other rat tissues examined. 3. Inhibition of 2- and 3-hexanol production from n-hexane by rat lung microsomes using metyrapone, an inhibitor of cytochrome P-450 2B1 activity, resulted in almost complete inhibition of lung microsomal activity. 4. Production of all three hexanols was significantly increased with phenobarbital-induced rat liver microsomes, with a 10-fold increase in 2- and 3-hexanol production. A slight increase in 2-hexanol production with phenobarbital-induced rat EDL and brain microsomes was observed. No increase in n-hexane metabolism was noted following induction with beta-naphthoflavone or with ethanol.