Environmental Occurrence, Toxicity Mechanism And Ahr-induced Risk Assessment Of Polybrominated Diphenyl Ethers (PBDEs) And Their Analogues

Due to their performance and cost-effectiveness, polybrominated diphenyl ethers (PBDEs), one kind of additive brominated flame retardants (BFRs), have been used for many years as flame retardants in various commercial products, such as furniture, textiles, plastics, paints, and electronic appliances. During their manufacturing, usage and treatment process, PBDEs can be easily released into environment and might cause adverse effects to human-being. Recently, PBDEs’two derivatives, hydroxylated polybrominated diphenyl ethers (HO-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs), have also been observed in various environmental matrixes. However, there is contradiction about their origins. To characterrize the occurrence of PBDEs and their derivatives in Yangtze River Delta, concentrations of PBDEs, HO-PBDEs and MeO-PBDEs were analyzed. Then, toxicity mechanisms of three typical compounds with highest detection rate were assessed by use of toxicogenomic tools. Finally, considering their structural similarity between PBDEs derivatives and dioxin-like compounds, dioxin-like activity and the related risk assessment of PBDEs derivatives were also assessed. Conclusions were described as following:i) Concentrations of13PBDEs and34PBDEs analogues were quantified in fish from two typical locations, sea (Yellow Sea) and inland lake or river (Yangtze River and Tai Lake). Concentration ofBDEs in marine fish (1.8to2.3×101ng/g lipid) was5.76fold lower than those in fish from Yangtze River (1.8to1.4×102ng/g lipid). These results suggest that the Yangtze River was more polluted by synthetic chemicals than those from the marine environment. Most interestingly, PBDEs analogues were detected only in sea fishes, except for the bigmouth grenadier anchovy, which is a migratory fish that resides in the Yangtze River estuary and migrates back to the Yangtze River to spawn. We speculated that MeO-PBDEs and HO-PBDEs may be from natural sources that produced by marine orgainisms. Three aquatic samples collected between2009and2012in Tai Lake were also analyzed for the PBDEs. And no significant difference was observed between concentrations of PBDEs of each year. However, there was a significant biomagnification among different trophic levels. Concentrations of PBDEs in organisms from Yangtze River Delta were less that from other countries of districts, and concentrations of PBDEs derivatives were almost equal to that from other places.ii) A new toxicogenomic tool, live cell array, was developed to assess the toxicological mechanism of PBDEs and their derivatives, which involved most of the genome in E. coli K12strains. Firstly, cytotoxicity of34PBDEs analogues were assessed by exposure to E. coli K12strains. Secondly, only HO-PBDEs can cause toxicity to bacteria. Based on their cytotoxicity, occurrence and structure difference, associated molecular mechanisms of three typical chemicals (BDE-47,6-HO-BDE-47and6-MeO-BDE-47) were assessed by use of a live cell reporter assay system which contains a library of1820modified green fluorescent protein (GFP) expressing promoter reporter vectors constructed from E. coli K12strains.6-HO-BDE-47inhibited growth of E. coli with a4h median effect concentration (EC50) of22.52±2.20mg/L, but neither BDE-47nor6-MeO-BDE-47were cytotoxic within4h. Exposure to6-HO-BDE-47, the most toxic one, resulted in65(fold change>2) or129 (fold change>1.5) genes being differentially expressed. The no observed transcriptional effect concentration (NOTEC) and median transcriptional effect concentration (TEC50) of6-HO-BDE-47were0.0438and0.580mg/L, respectively at4h. The transcriptional responses were514-and39-fold more sensitive than the traditional acute LC50to inhibit cell growth. Based on KEGG database, three pathways, including the metabolic pathway, phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS) and aminoacyl-tRNAs, were identified as being most responsive to6-HO-BDE-47during the4h exposure. Most of the genes that were differentially expressed in response to6-HO-BDE-47were not modulated by BDE-47or6-MeO-BDE-47. These results suggest that cytotoxicity of6-HO-BDE-47to E. coli was via a mechanism that was different from that of either BDE-47or6-MeO-BDE-47.iii) Dioxin-like activity of PBDEs derivatives was evaluated by use of the H4IIE-luc, a rat hepatoma cell based transactivation bioassay and their human health risk assessment was also conducted based on their dioxin-like activity. Among the34tested analogues (0to10000ng/ml) of PBDEs,19activated the aryl hydrocarbon receptor (AhR) and induced significant dioxin-like responses in H4IIE-luc cells. Efficacies of the analogues of PBDEs ranged from5.0%to101.8%of the maximum caused by2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD-max) and their respective2,3,7,8-TCDD potency factors (RePH4IIE-luc) ranged from7.35×10-12to4.00×10-4, some of which were equal to or more potent than some mono-ortho-substituted PCBs (TEFWHO=3×10-5). HO-PBDEs exhibited greater dioxin-like activity than did the corresponding MeO-PBDEs. Concentrations of2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (PBDEsanaloguesTEQH4IIE-luc) of the samples were also calculated as the sum of the product of concentrations of individual PBDE and their RePH4IIE-luc, which were less than the tolerance limit proposed by European Union and the oral reference dose (RfD) derived by U.S. Environmental Protection Agency, respectively,(Hazard Quotients (HQ)<0.005)...