Body Burdens of Polychlorinated Dibenzo- p -dioxins, Dibenzofurans, and Biphenyls and Their Relations to Estrogen Metabolism in Pregnant Women

Abstract

Polychlorinated dibenzo-p-dioxins (PCDDs, dioxins), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are environmental endocrine disruptors that have half-lives of 7–10 years in the human body and have toxicities that probably include carcinogenesis. A high ratio of 4-hydroxyl estradiol (4-OH-E2) to 2-hydroxyl estradiol (2-OH-E2) has been suggested as a potential biomarker for estrogen-dependent neoplasms. In this cohort study of maternal–fetal pairs, we examined the relationship of PCDD/PCDF and PCB exposure to levels of estrogen metabolites in the sera of 50 pregnant women 25–34 years of age from central Taiwan. Maternal blood was collected during the third trimester, and the placenta was collected at delivery. We measured 17 dioxin congeners, 12 dioxin-like PCBs, and 6 indicator PCBs in placenta using gas chromatography coupled with high-resolution mass spectrometry. Estrogen metabolites in maternal serum were analyzed by liquid chromatography tandem mass spectrometry. The ratio of 4-OH-E2:2-OH-E2 decreased with increasing exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (β = −0.124, p = 0.004 by the general linear regression model, R = 0.4). Meanwhile, serum levels of 4-OH-E2 increased with increasing concentrations of high-chlorinated PCDFs (i.e., 1,2,3,4,6,7,8-hepta-CDF: β = 0.454, p = 0.03, R = 0.30). Altered estrogen catabolism might be associated with body burdens of PCDDs/PCDFs. Our study suggests that exposure to PCDDs/PCDFs significantly affects estrogen metabolism. Therefore, PCDD/PCDF exposure must be considered when using the OH-E2 ratio as a breast cancer marker.

Increased Risk of Diabetes and Polychlorinated Biphenyls and Dioxins

“…PCDFs, and some PCBs, can induce CYP1A1 and CYP1B1 gene expression by serving as aryl-hydrocarbon receptor agonists (19). CYP1A1 and CYP1B1 catalyze hydroxylation of the Aring of estradiol (E 2 ) to form the catechol estrogen 2-or 4-hydroxyl estradiol (2-OH-E 2 or 4-OH-E 2 , respectively), which may be altered by exposure to dioxins (20). The metabolism of 4-OH-E 2 via redox-active compounds generates free radicals, such as reactive semiquinone intermediates.…”

“…In addition, metabolism of PCB-and DF-related genes, such as CYP1A, CYP1B, and CYP11B (19,20), may relate to the development of chloracne and later chronic conditions of hyperglycemia and hypertension. Further study of these genetic polymorphisms related to the effect of susceptibility is suggested.…”

Estimating perchlorate exposure from food and tap water based on US biomonitoring and occurrence data

“…This action contrasts with the non-dioxin like PCBs and their metabolites, which may have direct estrogenic action Wang et al, 2006;Yoshida et al, 2005). Dioxin and other organochlorine chemicals have been shown to interfere with male and female reproductive development in experimental and wild animals, particularly during gestational exposure (Gao et al, 1999;Grey and Ostby, 1995;Roman et al, 1998;Sonne et al, 2006;Theobald et al, 1997).…”

Upstream adverse effects in risk assessment: A model of polychlorinated biphenyls, thyroid hormone disruption and neurological outcomes in humans

“…PCBs are well known to affect neurodevelopmental outcomes in humans (Schantz et al, 2003), and additional mechanisms may be important. For example, some PCB (and OH-PCB) congeners are estrogenic (Matthews et al, 2007;Wang et al, 2006). Some PCB congeners bind to the ryanodine receptor with high affinity and can alter calcium signaling in cells of the central nervous system (Pessah et al, 2009;Yang et al, 2009).…”