Microarray analysis reveals a mechanism of phenolic polybrominated diphenylether toxicity in zebrafish

Polybrominated diphenylethers (PBDEs) are ubiquitous in the environment, with the lower brominated congener 2,2′,4,4′-tetrabromodiphenylether (BDE47) among the most prevalent The phenolic PBDE, 6-hydroxy-BDE47 (6-OH-BDE47) is both an important metabolite formed by in vivo metabolism of BDE47 and a natural product produced by marine organisms such as algae. Although this compound has been detected in humans and wildlife, including fish, virtually nothing is known of its in vivo toxicity. Here we report that 6-OH-BDE47 is acutely toxic in developing and adult zebrafish atconcentrations in the nanomolar (nM) range. To identify possible mechanisms of toxicity, we used microarray analysis as a diagnostic tool. Zebrafish embryonic fibroblast (PAC2) cells were exposed to 6-OH-BDE47, BDE47, and the methoxylated metabolite 6-MeO-BDE47. These experiments revealed that 6-OH-BDE47 alters the expression of genes involved in proton transportand carbohydrate metabolism. These findings, combined with the acute toxicity, suggested that 6-OH-BDE47 causes disruption of oxidative phosphorylation (OXPHOS). Thereto re, we further investigated the effect of 6-OH-BDE47 on OXPHOS in zebrafish mitochondria. Results show unequivocally that this compound is a potent uncoupler of OXPHOS and is an inhibitor of complex II of the electron transport chain. This study provides the first evidence of the in vivo toxicity and an important potential mechanism of toxicity of an environmentally relevant phenolic PBDE of both anthropogenic and natural origin. The results of this study emphasize the need for further investigation on the presence and toxicity of this class of polybrominated compounds. © 2008 American Chemical Society

Determination of halogenated natural products in passive samplers deployed along the Great Barrier Reef, Queensland/Australia

Halogenated natural products (HNPs) have been increasingly reported to occur in marine wildlife from all oceans. Several HNPs, such as 2,3,3′,4,4′,5,5′-heptachloro-1′-methyl-1,2′-bipyrrole (Q1) and 4,6-dibromo-2-(2′,4′-dibromo)phenoxyanisole (2′-MeO-BDE 68 or BC-2), were detected at particularly high concentrations in dolphins from Queensland/Australia. About half of the coastline of Queensland (2500 km) is covered by the Great Barrier Reef, a rich ecosystem hosting a huge variety of species, many of which are known to produce natural compounds. In this study, semipermeable membrane devices (SPMDs) were deployed as passive samplers for about 30 days at 12 marine and 2 nonmarine sites (i.e., rivers) along the Great Barrier Reef as part of a routine monitoring program during November 2007 and May 2008. Q1 and 2′-MeO-BDE 68 were detected at the marine sites with frequencies of about 65% but not in any sample from the two rivers. Further HNPs (2,4,6-tribromophenol, TBP; 2,4,6-tribromoanisole, TBA; 2,2′-dimethoxy-3,3′5,5′-tetrabromobiphenyl, 2,2′-diMeO-BB 80 or BC-1; 3,5-dibromo-2-(2′,4′-dibromo)phenoxyanisole, 6-MeO-BDE 47 or BC-3; and 3,5-dibromo-2-(3′,5′-dibromo,2′-methoxy)phenoxyanisole, 2′,6-diMeO-BDE 68 or BC-11) were detected as well with frequencies of 18−97% in the marine samples, but no polybrominated flame retardants were detected. The highest amount of a single HNP, 2.3 μg/SPMD, was determined for TBP, which had a frequency of detection of only 46%. The maximum (average) amount in the SPMDs from marine sites was 44 ng (12 ng) for Q1 and 115 ng (20 ng) for 2′-MeO-BDE 68. A first order kinetic model was used to estimate concentrations of the HNPs in the water phase. Based on the depuration of performance reference compounds obtained at one of the sites, we assumed a sampling rate of 16 L/day. We used this sampling rate to estimate that the highest and average available concentrations of Q1 in the water during the deployment of the SPMD were 97 and 25 pg/L, respectively. The estimated maximum water concentrations of 2′-MeO-BDE 68, 2,2′-diMeO-BB 80, 6-MeO-BDE 47, and 2′,6-diMeO-BDE 68 were on average 2−5.5 fold higher than that of Q1. The results confirm that the HNPs are produced throughout the Great Barrier Reef, which appears to be a significant source of these compounds