Development of TEFs for PCB congeners by using an alternative biomarker--thyroid hormone levels

Regul Toxicol Pharmacol. 2010 Mar;56(2):225-36. doi: 10.1016/j.yrtph.2009.12.008. Epub 2010 Jan 1.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Milk, Human / drug effects
  • Milk, Human / metabolism
  • Polychlorinated Biphenyls / chemistry*
  • Polychlorinated Biphenyls / toxicity*
  • Rats
  • Rats, Inbred Lew
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Species Specificity
  • Thyroid Hormones / genetics
  • Thyroid Hormones / metabolism*
  • Toxicity Tests / methods
  • Toxicity Tests / trends*

Substances

  • Biomarkers
  • Thyroid Hormones
  • Polychlorinated Biphenyls