Impacts of Unregulated Novel Brominated Flame Retardants on Human Liver Thyroid Deiodination and Sulfotransferation.

Journal Article

The inhibitory effects of five novel brominated flame retardants, 1,2-bis(2,4,5-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), and β-tetrabromoethylcyclohexane (β-TBECH), on thyroid hormone deiodinase (DIO) and sulfotransferase (SULT) activity were investigated using human in vitro liver microsomal and cytosolic bioassays. Enzymatic activity was measured by incubating active human liver subcellular fractions with thyroid hormones (T4 and rT3 separately) and measuring changes in thyroid hormone (T4, T3, rT3, and 3,3'-T2) concentrations. Only DBDPE showed inhibition of both outer and inner ring deiodination (O and IRD) of T3 and 3,3'-T2 formation from T4, respectively, with an estimated IC50 of 160 nM; no statistically significant inhibition of SULT activity was observed. ORD inhibition of 3,3'-T2 formation from rT3 was also observed (IC50 ∼ 100 nM). The kinetics of T4 O and IRD were also investigated, although a definitive mechanism could not be identified as the Michaelis-Menten parameters and maximal rate constants were not significantly different. Concentrations tested were intentionally above expected environmental levels, and this study suggests that these NBFRs are not potent human liver DIO and SULT inhibitors. To our knowledge, DBDPE is the first example of a nonhydroxylated contaminant inhibiting DIO activity, and further study of the mechanism of action is warranted.

Full Text

Duke Authors

Cited Authors

  • Smythe, TA; Butt, CM; Stapleton, HM; Pleskach, K; Ratnayake, G; Song, CY; Riddell, N; Konstantinov, A; Tomy, GT

Published Date

  • June 2017

Published In

Volume / Issue

  • 51 / 12

Start / End Page

  • 7245 - 7253

PubMed ID

  • 28541672

Electronic International Standard Serial Number (EISSN)

  • 1520-5851

International Standard Serial Number (ISSN)

  • 0013-936X

Digital Object Identifier (DOI)

  • 10.1021/acs.est.7b01143

Language

  • eng