Biotransformation of Dec-604 and potential effect on thyroid deiodinase activity in highly flame retardant-exposed gulls

Abstract

Several halogenated flame retardants (HFRs) have been identified as thyroid disruptors in birds including the polybrominated diphenyl ether (PBDE) mixtures, which have been replaced with other HFRs such as Dechlorane-604 (Dec-604). Dec-604 Component B (Dec-604 CB), a putative debrominated product of Dec-604, has been frequently reported in urban-adapted ring-billed gulls (Larus delawarensis) breeding in the Montreal area (QC, Canada). The metabolic pathways of Dec-604 are yet to be characterized, although the occurrence of Dec-604 CB in gulls may suggest that enzyme-mediated dehalogenation may occur, potentially involving the thyroid deiodinases. The objective of this study was to investigate the effect of Dec-604 on type 1 deiodinase (DIO1) in the presence of thyroxine (T₄) in an in vitro DIO1 assay using liver microsomes of ring-billed gulls that are highly exposed to HFRs in the Montreal area, and to determine whether DIO1 is involved in the in vitro debromination of Dec-604. We tested the in vitro activity of DIO1 in gull liver microsomes in the presence of five concentrations of Dec-604 ranging from 0.86 to 86.21 nM. HFR concentrations (Σ₄₀HFR) were also determined in liver samples of gulls. Results showed that total DIO1 activity in gull liver microsomes was increased by three of the five concentrations of Dec-604. No relationship between liver Σ₄₀HFR concentrations and DIO1 activity was observed, except for T₂ formation rates that significantly decreased with increasing liver HFR concentrations. Moreover, greater Dec-604 CB to Dec-604 concentration ratios in activated gull microsomes (with the DIO1 cofactor dithiothreitol) were found at the intermediate Dec-604 concentration compared to controls. These results suggested that liver microsome DIO1 activity may be perturbed in ring-billed gulls exposed to Dec-604, and be involved at least in part, in the debromination of Dec-604 leading to the formation of Dec-604 CB.

Keywords: Biotransformation; Bird; Dechlorane; Halogenated flame retardant; In vitro assay.