Effect of phenobarbital, naphthoflavone and diethlmaleate on the sex dependent urinary pattern of hexachlorobenzene metabolites in the rat

The sex related difference in the urinary excretion of pentachlorothiophenol (PCThP) was investigated in rats after a single oral dose of hexachlorobenzene (HCB) and compared to that obtained after a single oral dose of pentachloronitrobenzene (PCNB). A ten fold difference was obtained in both cases in favour of females. The effect of phenobarbital (PB) and β-naphtoflavone (β–NF) and the effect of diethylmaleate (DM) on the urinary pattern of HCB metabolites was investigated in male and female rats. PB enhanced the urinary excretion of pentachlorophenol (PCP) and tetrachlorohydroquinone (TCHQ) but had no effect on the excretion of PCThP. β-NF did not have any effect on any of the three main metabolites while an hepatic glutathione depletion induced by DM significantly reduced the excretion of PCThP in females. The results suggest that, after HCB or PCNB intake, a common sex dependent biotransformation step leads to the formation of PCThP, after conjugation with glutathione, independently of the pathway leading to the formation of PCP which is under the control of a PB inducible form of cytochrome P-450.