Hydroxylated PCBs (OH‐PCBs) as potential endocrine disrupters ‐ exposures and toxic effects

Abstract

Background: Lipophilic and persistent environmental pollutants such as polychlorinated biphenyls are well known to accumulate in wildlife and human adipose tissue. The compounds are however more or less rapidly metabolised and eliminated from the body as water soluble conjugates unless the compounds are transformed to reactive intermediates leading to non‐reversible binding of the substances to biomacromolecules, to other persistent and lipophilic metabolites such as aryl methyl sulfones or transformed to metabolites with specific protein (receptor) binding properties. Hydroxylated PCB (OH‐PCBs) metabolites have been shown to bind to the thyroxine transporting protein transthyretin (TTR) and thus potentially act as endocrine disrupters. Results and Discussion: In the present study the occurrence of OH‐PCBs that are retained in human serum has been studied. As many as 26 OH‐PCBs have been identified and in addition several other halogenated monocyclic phenols have been identified in the human blood. Major OH‐PCBs have been quantified in a cohort of men living around the Baltic Sea eating variable amounts of fat fish from this contaminated area. Comparisons were made to the levels of other major environmental pollutants, incl. PCB. The relative amounts of 10–20% of OH‐PCB to PCB congeners indicate that this type of PCB metabolites may be of toxico‐logical significance. Several of the OH‐PCBs and other phenols have been shown to be potent competitors for thyroxine binding to TTR. Also, one of the dominating OH‐PCB metabolites, 2,3,3′,4′,5‐pentachloro‐4‐biphenylol (4‐OH‐CB107) has been shown to dramatically reduce plasma thyroid hormone levels (>90%) in fetal rats. Further, 4‐OH‐CB107 has been shown to affect the behavioural outcome as well as the reproductive cycle (i.e., prolonged diestrous) in rat offspring exposed to 4‐OH‐CB107 in utero.