title: Development of TEFs for PCB congeners by using an alternative biomarker--thyroid hormone levels.
abstract: Polychlorinated biphenyls (PCBs) are ubiquitous toxic contaminants. Health risk assessment for this class of chemicals is complex: the current toxic equivalency factor (TEF) method covers dioxin-like (DL-) PCBs, dibenzofurans, and dioxins, but excludes non-DL-PCBs. To address this deficiency, we evaluated published data for several PCB congeners to determine common biomarkers of effect. We found that the most sensitive biomarkers for DL-non-ortho-PCB 77 and PCB 126 are liver enzyme (e.g., ethoxyresorufin-O-deethylase, EROD) induction, circulating thyroxine (T4) decrease, and brain dopamine (DA) elevation. For DL-ortho-PCB 118 and non-DL-ortho-PCB 28 and PCB 153, the most sensitive biomarkers are brain DA decrease and circulating T4 decrease. The only consistent biomarker for both DL- and non-DL-PCBs is circulating T4 decrease. The calculated TEF-(TH), based on the effective dose to decrease T4 by 30% (ED(30)) with reference to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is identical to both TEF-(WHO98) and TEF-(WHO05) for TCDD and DL-PCBs (correlation coefficients are r=1.00, P<0.001; and r=0.99, P<0.001, respectively). We conclude that T4 decrease is a prospective biomarker for generating a new TEF scheme which includes some non-DL-congeners. The new TEF-(TH) parallels the TEF-(WHO) for DL-PCBs and, most importantly, is useful for non-DL-PCBs in risk assessment to address thyroid endocrine disruption and potentially the neurotoxic effects of PCBs.
authors.affiliation: Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA 94612, USA. jyang@oehha.ca.gov
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Yang
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Salmon
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Marty
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008895:Milk, Human / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000737:chemistry* / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D018675:Toxicity Tests / Q000379:methods / Q000639:trends*
chemical_list: D015415:Biomarkers; D013963:Thyroid Hormones; D011078:Polychlorinated Biphenyls