Comparison of the urinary metabolite profiles of hexachlorobenzene and pentachlorobenzene in the rat

Abstract

The urinary metabolite profile of hexachlorobenzene (HCB) and pentachlorobenzene (PCBz) in the rat is compared after dietary exposure for 13 weeks. Both HCB and PCBz are oxidized to pentachlorophenol (PCP) and tetrachlorohydroquinone (TCHQ), which were the only two mutual metabolites formed. Additional urinary metabolites of HCB are N-acetyl- S(pentachlorophenyl)cysteine (PCTP-NAC), which appeared to be quantitatively the most important product, and mercaptotetrachlorothioanisole (MTCTA), which was excreted as a glucuronide. PCBz is more extensively metabolized to the major metabolites 2,3,4,5-tetrachlorophenol (TCP), mercaptotetrachlorophenol (MTCP) and the glucuronide of pentachlorothiophenol (PCTP), and the minor metabolites methylthiotetrachlorophenol (MeTTCP), hydroxytetrachlorophenyl sulphoxide (HTCPS), and bis(methylthio)-trichlorophenol ( bis-MeTTriCP). The biotransformation of HCB and PCBz was modulated by selective inhibition of cytochrome P450IIIA in rats which received combined treatment of HCB or PCBz with triacetyloleandomycin (TAO). Rats receiving this diet had a strongly diminished excretion of both PCP and TCHQ, as compared to rats fed HCB or PCBz alone, indicating the involvement of P450IIIA in the oxidation of both compounds. However, the excretion of 2,3,4,5-TCP was not diminished by co-treatment of rats with PCBz and TAO, indicating that: (i) the oxidation of PCBz to PCP and 2,3,4,5-TCP does not proceed via a common intermediate; and (ii) oxidation of PCBz to 2,3,4,5-TCP is not mediated by P450IIIA. Co-treatment of rats with PCBz and TAO had a differential effect on the excretion of sulphur-containing metabolites, resulting in a decrease in the excretion of PCTP glucuronide, whereas no change was observed in the excretion of MTCP, as compared to rats receiving PCBz alone. The observed differences in HCB and PCBz metabolites clearly deserve further in vitro studies to elucidate their origin.