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It was hypothesized that polychlorinated diphenyl sulfides (PCDPSs) can potentially interact with an aryl hydrocarbon receptor (AHR) and thereby cause adverse effects in wildlife like birds. A recently developed avian AHRl-luciferase report gene (LRG) assay was used to assess the interaction between avian AHR1 and 18 PCDPSs and to compare the interspecies sensitivity among chicken, ring-necked pheasant, and Japanese quail by PCDPSs. Most of the tested PCDPSs could activate the AHR1-mediated pathways in avian species, and the relative potency (ReP) of the PCDPSs increased with the increasing number of substituted Cl atoms. The rank orders of PCDPSs potency were generally similar among birds, although the ReP varied. In addition, not all the sensitivity rank orders of avian AHR1 constructs for PCDPSs were consistent with that of TCDD. ReP values of PCDPSs suggested that some PCDPSs like 2,3,3',4,5,6-hexa-CDPS and 2,2',3,3',4,5,6-hepta-CDPS are higher than the avian WHO-TEFs of OctaCDD, OctaCDF, and most of the coplanar PCBs. Our results report for the first time the activation of an AHR1-mediated molecular toxicological mechanism by PCDPSs, and provide the ranking of ReP and relative sensitivity values of different congeners, which could guide the further toxicity test of this group of potential high priority environmental pollutants. [ABSTRACT FROM AUTHOR]

The World Health Organization toxic equivalency factors (WHO-TEFs) for birds were developed to simplify risk assessments of environmental mixtures of dioxin-like compounds (DLCs). Under this framework, toxic equivalents (TEQs) are used to represent the toxic potency of DLC mixtures as an equivalent concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Recently, a luciferase reporter gene (LRG) assay, measuring aryl hydrocarbon receptor 1 (AHR1)-mediated gene expression, accurately predicted the relative potency of individual polychlorinated biphenyl (PCB) congeners in different avian species. The study presented here used the LRG assay to predict the relative potency of Aroclors 1016, 1221, 1242, 1248, 1254, and 1260 on induction of LRG activity in cells transfected with chicken, ring-necked pheasant, or Japanese quail AHR1 constructs. LRG assay results were compared to (1) results of ethoxyresorufin-O-deethylase (EROD) assays conducted in chicken hepatocytes and (2) calculated TEQs from the literature. The relative potencies of Aroclors were similar between the LRG and EROD assays, and bioassay-derived TEQs for the chicken closely resembled calculated TEQs. However, LRG assay-derived TEQs for the Japanese quail construct were 1-2 orders of magnitude higher than calculated TEQs for Aroclors 1254 and 1016. These results suggest that the WHO-TEFs are not representative of relative PCB potency for all avian species. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) and their analogues, such as hydroxylated PBDE (HO-PBDEs) and methoxylated PBDE (MeO-PBDEs) are of interest due to their wide distribution, bioaccumulation and potential toxicity to humans and wildlife. While information on the toxicity/biological potencies of PBDEs was available, information on analogues of PBDEs was limited. Dioxin-like toxicity of 34 PBDEs analogues was evaluated by use of the H4IIE-luc, rat hepatoma transactivation bioassay in 384-well plate format at concentrations ranging from 0 to 10 000 ng/mL. Among the 34 target analogues of PBDEs studied here, 19 activated the aryl hydrocarbon receptor (AhR) and induced significant dioxin-like responses in H4IIE-luc cells. Efficacies of the analogues of PBDEs ranged from 5.0% to 101.8% of the maximum response caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD-max) and their respective 2,3,7,8-TCDD potency factors (RePH4IIE-luc) ranged from 7.35 × 10-12 to 4.00 × 10-4, some of which were equal to or more potent than some mono-ortho-substituted PCBs (TEF-WHO = 3 × 10-5). HO-PBDEs exhibited greater dioxin-like activity than did the corresponding MeO-PBDEs. Analogues of PBDEs were detected mostly in marine organisms. Of these 11 detected analogues of PBDEs, 6 were found to have measurable dioxin-like potency. Though some analogues of PBDEs exhibited significant dioxin-like potency as measured by responses of the H4IIE-luc transactivation assay, concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (PBDEs analoguesTEQH4IIE-luc), calculated as the sum of the product of concentrations of individual PBDE and their RePH4IIE-luc, 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) Additional investigations should be conducted to evaluate the toxic potencies of these chemicals, especially for 2′-MeO-BDE-28, 4-HO-BDE-90, 6-HO-BDE-47, and 6-MeO-BDE-47, which had been detected in other environmental media, including human blood. [ABSTRACT FROM AUTHOR]