Hydroxylated polychlorinated Biphenyls (PCBs) and Organochlorine Pesticides as Potential Endocrine Disruptors

Abstract

Hydroxylated polychlorinated biphenyls (hydroxy-PCBs) and various organochlorine pesticides have been identified as environmental contaminants, and three has been some concernregarding their potential adverse effects as endocrine-active agents. Initial studies showed that two synthetic compounds, 2′,4′,6′-trichloro- and 2′,3′,4′,5′-tetrachloro-4-biphenylol (HO-PCB3 and HO-PCB4, respectively), bound to the estrogen receptor (ER) and exhibited estrogenic activity in both in vivo and in vitro assays. Although these compounds alone were weakly estrogenic (>1000 times less potent than 17β-estradiol), there were some reports suggesting that interactions of these compounds and several organochlorine pesticides were synergistic. Subsequent studies in this laboratory have confirmed that HO-PCB3 and HO-PCB4 were weakly estrogenic and equimolar concentartios of these compounds gave additive responses. Similar results were obtained for organochlorine pesticides. Structure-activity relationships for hydroxy-PCBs showed that most compounds were either weakly estrogenic or inactive; moreover, several compounds exhibited antiestrogenic activity. Based on their weak estrogenic potencies and low environmental levels, it is unlikely that hydroxy-PCB and organochlorine pesticides contribute significantly to overall xenoestrogen action.