Metabolic Activation of Nonpolar Sediment Extracts Results in enhanced Thyroid Hormone Disrupting Potency

M. Montano, J. Weiss, L. Hoffmann, A.C. Gutleb, A.J. Murk

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

Abstract

Traditional sediment risk assessment predominantly considers the hazard derived from legacy contaminants that are present in nonpolar sediment extracts, such as polychlorinated biphenyls (PCBs), dioxins, furans (PCDD/Fs), and polyaromatic hydrocarbons (PAHs). Although in vivo experiments with these compounds have shown to be thyroid hormone disrupting (THD), in vitro their THD potency is not observed in nonpolar sediment extracts. This is hypothesized to be due to the absence of in vitro biotransformation which will result in bioactivation of the lipophilic compounds into THD hydroxyl metabolites. This study reveals that indeed metabolically activated nonpolar contaminants in sediments can competitively bind to thyroid hormone transport proteins. Sediment fractions were incubated with S9 rat microsomes, and the metabolites were extracted with a newly developed method that excludes most of the lipids to avoid interference in the applied nonradioactive 96-well plate TTR competitive binding assay. Metabolic activation increased the TTR binding potency of nonpolar fractions of POP-polluted sediments up to 100 times, resulting in potencies up to 240 nmol T4 equivalents/g sediment equivalent (nmol T4-Eq/g SEQ). This demonstrates that a more realistic in vitro sediment THD risk characterization should also include testing of both polar and medium polar sediment extracts for THD, as well as bioactivated nonpolar sediment fractions to prevent underestimation of its toxic potency.
Original languageEnglish
Pages (from-to)8878-8886
JournalEnvironmental Science and Technology
Volume47
Issue number15
DOIs
Publication statusPublished - 2013

Keywords

  • persistent organic pollutants
  • brominated flame retardants
  • effect-directed analysis
  • halogenated aromatic-hydrocarbons
  • polybrominated diphenyl ethers
  • in-vitro
  • polychlorinated-biphenyls
  • endocrine disruption
  • estrogenic activity
  • hepatic microsomes

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