The organochlorine compound, pentachlorophenol (PCP), is classified as a hazardous substance. Its metabolite, tetrachloro-1,2-hydroquinone (TCHQ), has been detected in occupationally-exposed subjects and can readily be converted to tetrachloro-1,4-benzoquinone (TCBQ) under physiological conditions. Hazard characterization has previously
identified the liver as the target organ of PCP toxicity in rats and dogs and as the liver is the major site of metabolism of the parent compound, this raises concern for the effects that the metabolites of PCP may have on the liver. Although the hepatotoxic effects of PCP have been described, less is known about the effects of its metabolites on hepatocyte function.
Studying the effects of these metabolites on hepatocytes may provide valuable information regarding the effects that these compounds could exert on the liver itself and allude to the clinical manifestations of toxicity that can be expected. The aim of this study was therefore to assess the effect of PCP, TCHQ and TCBQ on the following cellular parameters: cell
viability, mitochondrial membrane potential and intracellular ROS formation, as indicators of hepatocyte homeostasis.
Both PCP and its metabolites, TCHQ and TCBQ decreased cell viability with IC50 of 68.05, 129.40 and 144.00 μM, respectively. All three compounds caused mitochondrial depolarization, with the effect being more profound following exposure to TCHQ and TCBQ. PCP did not induce any ROS generation, whereas TCHQ and TCBQ produced extensive ROS. Findings from this study suggest that in hepatocytes the mechanism of toxicity of PCP differs from that of its metabolites, TCHQ and TCBQ.