Deriving a water quality guideline for protection of aquatic communities exposed to triclosan in the Canadian environment.

Triclosan is an antibacterial and antifungal chemical used in a variety of consumer products, including soaps, detergents, moisturizers, and cosmetics. Aquatic ecosystems may be exposed to triclosan following the release of remaining residues in wastewater effluents and biosolids. In December 2017, Environment and Climate Change Canada (ECCC) released a federal environmental quality guideline (FEQG) report that contained a federal water quality guideline (FWQG) for triclosan. This guideline will be used as an adjunct to the risk assessment and risk management of priority chemicals identified under the Government of Canada's Chemicals Management Plan (CMP). The FWQG value for triclosan (0.47 µg/L) was derived by ECCC using a hazardous concentration for 5% of species (HC5) from a species sensitivity distribution (SSD). We recalculated the FWQG after performing an independent analysis and evaluation of the available aquatic toxicity data for triclosan and compared our results with the ECCC FWQG value. Our independent analysis of the available aquatic toxicity data entailed conducting a literature search of all available and relevant studies, evaluating the quality and reliability of all studies considered using thorough and consistent study evaluation criteria, and thereby generating a data set of high-quality toxicity values. The selected data set includes 22 species spanning 5 taxonomic groups. An SSD was developed using this data set following the ECCC approaches. The HC5 from the SSD derived based on our validated data set is 0.76 µg/L. This HC5 value is slightly greater (i.e., less sensitive) than the value presented in ECCC's final FWQG. Integr Environ Assess Manag 2018;14:437-441. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

A refined ecological risk assessment for California red-legged frog, Delta smelt, and California tiger salamander exposed to malathion.

The California red-legged frog (CRLF), Delta smelt (DS), and California tiger salamander (CTS) are 3 species listed under the United States Federal Endangered Species Act (ESA), all of which inhabit aquatic ecosystems in California. The US Environmental Protection Agency (USEPA) has conducted deterministic screening-level risk assessments for these species potentially exposed to malathion, an organophosphorus insecticide and acaricide. Results from our screening-level analyses identified potential risk of direct effects to DS as well as indirect effects to all 3 species via reduction in prey. Accordingly, for those species and scenarios in which risk was identified at the screening level, we conducted a refined probabilistic risk assessment for CRLF, DS, and CTS. The refined ecological risk assessment (ERA) was conducted using best available data and approaches, as recommended by the 2013 National Research Council (NRC) report "Assessing Risks to Endangered and Threatened Species from Pesticides." Refined aquatic exposure models including the Pesticide Root Zone Model (PRZM), the Vegetative Filter Strip Modeling System (VFSMOD), the Variable Volume Water Model (VVWM), the Exposure Analysis Modeling System (EXAMS), and the Soil and Water Assessment Tool (SWAT) were used to generate estimated exposure concentrations (EECs) for malathion based on worst-case scenarios in California. Refined effects analyses involved developing concentration-response curves for fish and species sensitivity distributions (SSDs) for fish and aquatic invertebrates. Quantitative risk curves, field and mesocosm studies, surface-water monitoring data, and incident reports were considered in a weight-of-evidence approach. Currently, labeled uses of malathion are not expected to result in direct effects to CRLF, DS or CTS, or indirect effects due to effects on fish and invertebrate prey. Integr Environ Assess Manag 2018;14:224-239. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Relative potencies of aroclor mixtures derived from avian in vitro bioassays: comparisons with calculated toxic equivalents.

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.

Amino acid sequence of the ligand-binding domain of the aryl hydrocarbon receptor 1 predicts sensitivity of wild birds to effects of dioxin-like compounds.

The sensitivity of avian species to the toxic effects of dioxin-like compounds (DLCs) varies up to 1000-fold among species, and this variability has been associated with interspecies differences in aryl hydrocarbon receptor 1 ligand-binding domain (AHR1 LBD) sequence. We previously showed that LD(50) values, based on in ovo exposures to DLCs, were significantly correlated with in vitro EC(50) values obtained with a luciferase reporter gene (LRG) assay that measures AHR1-mediated induction of cytochrome P4501A in COS-7 cells transfected with avian AHR1 constructs. Those findings suggest that the AHR1 LBD sequence and the LRG assay can be used to predict avian species sensitivity to DLCs. In the present study, the AHR1 LBD sequences of 86 avian species were studied, and differences at amino acid sites 256, 257, 297, 324, 337, and 380 were identified. Site-directed mutagenesis, the LRG assay, and homology modeling highlighted the importance of each amino acid site in AHR1 sensitivity to 2,3,7,8-tetrachlorodibenzo-p-dioxin and other DLCs. The results of the study revealed that (1) only amino acids at sites 324 and 380 affect the sensitivity of AHR1 expression constructs of the 86 avian species to DLCs and (2) in vitro luciferase activity of AHR1 constructs containing only the LBD of the species of interest is significantly correlated (r (2) = 0.93, p < 0.0001) with in ovo toxicity data for those species. These results indicate promise for the use of AHR1 LBD amino acid sequences independently, or combined with the LRG assay, to predict avian species sensitivity to DLCs.

Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: comparisons with AHR1-mediated reporter gene activity and in ovo toxicity.

Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species.

A luciferase reporter gene assay and aryl hydrocarbon receptor 1 genotype predict the LD50 of polychlorinated biphenyls in avian species.

Birds differ in sensitivity to the embryotoxic effects of polychlorinated biphenyls (PCBs), which complicates environmental risk assessments for these chemicals. Recent research has shown that the identities of amino acid residues 324 and 380 in the avian aryl hydrocarbon receptor 1 (AHR1) ligand binding domain (LBD) are primarily responsible for differences in avian species sensitivity to selected dibenzo-p-dioxins and furans. A luciferase reporter gene (LRG) assay was developed in our laboratory to measure AHR1-mediated induction of a cytochrome P450 1A5 reporter gene in COS-7 cells transfected with different avian AHR1 constructs. In the present study, the LRG assay was used to measure the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and PCBs 126, 77, 105 and 118 on luciferase activity in COS-7 cells transfected with AHR1 constructs representative of 86 avian species in order to predict their sensitivity to PCB-induced embryolethality and the relative potency of PCBs in these species. The results of the LRG assay indicate that the identity of amino acid residues 324 and 380 in the AHR1 LBD are the major determinants of avian species sensitivity to PCBs. The relative potency of PCBs did not differ greatly among AHR1 constructs. Luciferase activity was significantly correlated with embryolethality data obtained from the literature (R(2)≥0.87, p<0.0001). Thus, the LRG assay in combination with the knowledge of a species' AHR1 LBD sequence can be used to predict PCB-induced embryolethality in potentially any avian species of interest without the use of lethal methods on a large number of individuals.