Analytical chemistry of hydroxylated metabolites of PCBs and other halogenated phenolic compounds in blood and their relationship to thyroid hormone and retinol homeostasis in humans and polar bears

Metabolites of xenobiotic compounds have been identified and monitored but were always thought to be excretion products and regarded as having little toxicological significance. Polychlorinated biphenyl (PCB) metabolites were discovered almost immediately after the discovery of PCBs but it was not until 20 years later, their significance was determined. Analytical methodology for hydroxylated metabolites of PCBs (OH-PCBs) was established for blood and plasma and applied to the analysis of polar bears and human plasma. During method development, a new chlorinated phenolic compound was discovered and its identity determined as a likely metabolite of octachlorostyrene. Polar bear plasma from Resolute Bay, Canada and Svalbard, Norway were found to have the highest levels of OH-PCBs of any species analyzed. Concentrations of OH-PCBs often exceeded the concentration of PCBs themselves making OH-PCBs the most abundalit class of contaminants in polar bear plasma. In polar bears, OH-PCBs were found to be positively associated with plasma retinol concentrations (r = +0.31, p = 0.02, n = 57) and negatively associated with the plasma free T4 index (r = −0.44, p < 0.001, n = 55) possibly indicating disruption of retinol and thyroid hormone homeostasis.; OH-PCBs and other halogenated phenolic compounds were also analyzed in Inuit whole blood and human umbilical cord plasma for the first time. Patterns and concentrations were determined for each. Pentachlorophenol was concluded to be one of the most important compounds in the phenolic compound fraction due to its high concentration in all human blood samples analyzed.