Sequence and In Vitro Function of Chicken, Ring-Necked Pheasant, and Japanese Quail AHR1 Predict In Vivo Sensitivity to Dioxins

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Dioxins and dioxin-like compounds (DLCs) are potent toxicants to most vertebrates. Sensitivities to DLCs vary among species. In the present study, the sensitivities of avian species (chicken [Gallus gallus], ring-necked pheasant [Phasianus colchicus], and Japanese quail [Coturnix japonica]) to some polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) were determined by using species-specific, in vitro, transactivation assays based on a luciferase reporter gene under control of species-specific aryl hydrocarbon receptors. In ring-necked pheasant and Japanese quail, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was not the most potent inducer of toxic effects. Especially for Japanese quail, the relative potency values of most of 9 PCDD/Fs tested were greater than for TCDD. The rank order of avian species sensitivities to DLCs was chicken > ring-necked pheasant > Japanese quail. Effects of binary mixtures of TCDD, 2,3,7,8-tetrachlorodibenzofuran, and 2,3,4,7,8-pentachlorodibenzofuran were strictly additive. Moreover, we also found that the primary DLCs that were responsible for most of the potency of the DLC mixtures can be deduced by using ordination in a multidimensional space defined by the avian species sensitivities. Overall, the relative potency and the species sensitivities of these chemicals could guide risk assessments to wild species when exposure to mixtures of DLCs in the environment.

Section: Resultssupporting

confidence: 91%

Relative sensitivities among avian species to individual and mixtures of aryl hydrocarbon receptor–active compounds

Wei

Zhang

et al. 2016

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“…However, some uncertainty exists regarding the application of the WHO TEF approach, and this approach has been suggested to not be sufficient for ecological risk assessment for this group of vertebrates. To date, relative potencies for dioxin‐like compounds in fishes is limited relative to relative potencies for species of birds and species of mammals . Great differences in relative potencies were observed in liver explants of rainbow trout, white sturgeon, lake sturgeon, and northern pike for PCDFs and PCBs, with rainbow trout having the least relative potencies for each of the dioxin‐like compounds tested in the present study (Table ).…”

Section: Discussionmentioning

confidence: 63%

“…However, the greatest differences in relative potencies among rainbow trout, white sturgeon, lake sturgeon, and northern pike were for TCDF. Differences in relative potencies for TCDF were up to 4‐fold and up to 3‐fold greater than differences in relative potencies for TCDF among species of birds and species of mammals, respectively . Rainbow trout had the lowest relative potency for TCDF, with TCDD being greater than 33‐fold more potent than TCDF in liver explants and in embryos (Table ) .…”

Section: Discussionmentioning

confidence: 98%

Cross‐species comparison of relative potencies and relative sensitivities of fishes to dibenzo‐p‐dioxins, dibenzofurans, and polychlorinated biphenyls in vitro

Eisner

Doering

Beitel

et al. 2015

Dioxin-like compounds of varying toxicities are found in complex mixtures. The toxic equivalency factor (TEF) approach was developed based on the potency of a dioxin-like compound relative to the potency of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) to streamline risk assessment. One limitation of the TEF approach is uncertainty regarding differences in the relative potency of dioxin-like compounds among different species. Relative potencies among fishes are limited, relative to relative potencies among birds and mammals, and TEFs for fishes are based entirely on the model species, rainbow trout (Oncorhynchus mykiss). An in vitro liver explant assay was used to characterize species-specific responses with regard to up-regulation of CYP1A transcript after exposure to 6 dioxin-like compounds in rainbow trout, white sturgeon (Acipenser transmontanus), lake sturgeon (Acipenser fulvescens), and northern pike (Esox lucius). Differences in sensitivities were observed among species after exposure to dioxin-like compounds. The relative potencies developed from liver explants of rainbow trout were comparable to relative potencies developed from embryo toxicity assays. Differences in relative potencies between species with the least and greatest relative potencies were up to 40-fold. To compare relative potencies among species, concentrations of dioxin-like compounds in fish eggs in the Fraser River and in Lake Ontario were used to calculate toxic equivalency quotients (TEQs) determined from TEFs or TCDD equivalents determined from relative potencies. The TEQs underestimated TCDD equivalents for white sturgeon, lake sturgeon, and northern pike, indicating uncertainty in application of TEFs to diverse fishes.

“…Egloff et al also reported a concordant induction of CYP1A4 in liver tissue of chicken embryos exposed via egg injection to BTBPE. We recently developed a luciferase reporter gene assay in our laboratory to measure AHR1‐mediated induction of a CYP1A reporter gene , and it would be useful to screen TCP, ATE, BTBPE, and DBDPE to further characterize this induction of a dioxin‐like response.…”

Section: Resultsmentioning

confidence: 99%

Use of an avian hepatocyte assay and the avian toxchip polymerse chain reaction array for testing prioritization of 16 organic flame retardants

Porter

Crump

Egloff

et al. 2014

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120

Risk assessors are challenged with the task of providing data for an increasing number of priority chemicals. High-throughput toxicity screening methods--which permit rapid determination of toxic, molecular, and/or biochemical effects of a wide range of chemicals--are essential to help meet this demand. The avian embryonic hepatocyte in vitro screening method has been utilized in the authors' laboratory to assess the effects of a wide range of environmental contaminants on cytotoxicity and mRNA expression of genes associated with xenobiotic metabolism, the thyroid hormone pathway, lipid metabolism, and growth. Sixteen structurally variable organic flame retardants (OFRs)--including tetrabromoethylcyclohexane (TBECH), tris(2-butoxyethyl) phosphate (TBEP), tricresyl phosphate (TCP), and tris(1,3-dichloro-2-propyl) phosphate (TDCPP)--were screened using the in vitro method in the present study. Hepatocytes from 2 avian species, chicken and herring gull, were prepared, and species differences in hepatocyte viability were observed for several OFRs. For example, TCP was not cytotoxic in chicken hepatocytes up to the highest concentration tested (300 µM), whereas the median lethal concentration (LC50) was 31.2 µM in herring gull hepatocytes. Effects on mRNA expression in chicken embryonic hepatocytes were determined using a 3 × 32 custom-made Avian ToxChip polymerse chain reaction array and were variable among OFRs; TCP, TDCPP, and tris(2,3-dibromopropyl) isocyanurate showed the most significant alterations among the target genes assessed. Overall, this rapid screening method helped prioritize OFRs for further assessment. For example, OFRs that elicited significant effects on cytoxicity or mRNA expression represent prime candidates for egg injection studies that determine adverse effects on the whole animal but are more costly in terms of time, money, and embryo utilization.