COMPARISON OF THE URINARY METABOLITE PROFILES OF HEXACHLOROBENZENE AND PENTACHLOROBENZENE IN THE RAT

The urinary metabolite profile of hexachlorobenzene (HCB) and pentachl orobenzene (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 metabol ites formed. Additional urinary metabolites of HCB are N-acetyl-S(pent achlorophenyl)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 metab olized to the major metabolites 2,3,4,5-tetrachlorophenol (TCP), merca ptotetrachlorophenol (MTCP) and the glucuronide of pentachlorothiophen ol (PCTP), and the minor metabolites methylthiotetrachlorophenol (MeTT CP), 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 w hich received combined treatment of HCB or PCBz with triacetyloleandom ycin (TAO). Rats receiving this diet had a strongly diminished excreti on of both PCP and TCHQ, as compared to rats fed HCB or PCBz alone, in dicating the involvement of P450IIIA in the oxidation of both compound s. However, the excretion of 2,3,4,5-TCP was not diminished by co-trea tment 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 intermediat e; and (ii) oxidation of PCBz to 2,3,4,5-TCP is not mediated by P450II IA. Co-treatment of rats with PCBz and TAO had a differential effect o n the excretion of sulphur-containing metabolites, resulting in a decr ease in the excretion of PCTP glucuronide, whereas no change was obser ved 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.