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).

Organophosphate triesters and selected metabolites enhance binding of thyroxine to human transthyretin in vitro.

The toxicological properties of organophosphate (OP) triesters that are used as flame retardants and plasticizers are currently not well understood, though increasing evidence suggests they can affect the thyroid system. Perturbation of thyroid hormone (TH) transport is one mechanism of action that may affect thyroid function. The present study applied an in vitro competitive protein binding assay with thyroxine (T4) and human transthyretin (hTTR) transport protein to determine the potential for the OP triesters, TDCIPP (tris(1,3-dichloro-2-propyl) phosphate), TBOEP (tris(butoxyethyl) phosphate), TEP (triethyl phosphate), TPHP (triphenyl phosphate), p-OH-TPHP (para-hydroxy triphenyl phosphate), and the OP diester DPHP (diphenyl phosphate), to competitively displace T4 from hTTR. Enhancement of T4 binding to hTTR, rather than the hypothesized competition, was observed for the six OP esters and in a concentration-dependent manner. For example, T4-hTTR binding was significantly increased at concentrations of TBOEP as low as 64 nM, and up to 184% of controls at 5000 nM. A plausible explanation of these results, which to our knowledge has not been previously reported, may be allosteric interactions of the OP esters with hTTR allowing T4 to access the second site of the TH binding pocket. These in vitro results suggest a novel mechanism of OP ester toxicity via T4 binding enhancement, and possible dysregulation of T4-hTTR interactions.

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).

In Vitro and in Silico Competitive Binding of Brominated Polyphenyl Ether Contaminants with Human and Gull Thyroid Hormone Transport Proteins.

Tetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) is a highly brominated additive flame retardant (FR). Debrominated photodegradates of TeDB-DiPhOBz are hydroxylated in vitro in liver microsomal assays based on herring gulls (Larus argentatus), including one metabolite identified as 4″-OH-2,2',2″,4-tetrabromo-DiPhOBz. Chemically related methoxylated tetra- to hexabromo-DiPhOBzs are known contaminants in herring gulls. Collectively, nothing is currently known about biological effects of these polybrominated (PB) DiPhOBz-based compounds. The present study investigated the potential thyroidogenicity of 2,2',2″,4-tetrabromo-(TB)-DiPhOBz along with its para-methoxy (MeO)- and hydroxy-(OH)-analogues, using an in vitro competitive protein binding assay with the human thyroid hormone (TH) transport proteins transthyretin (hTTR) and albumin (hALB). This model para-OH-TB-DiPhOBz was found to be capable of competing with thyroxine (T4) for the binding site on hTTR and hALB. In silico analyses were also conducted using a 3D homology model for gull TTR, to predict whether these TB-DiPhOBz-based compounds may also act as ligands for an avian TH transport protein despite evolutionary differences with hTTR. This analysis found all three TB-DiPhOBz analogues to be potential ligands for gull TTR and have similar binding efficacies to THs. Results indicate structure-related differences in binding affinities of these ligands and suggest there is potential for these contaminants to interact with both mammalian and avian thyroid function.

Optimization of an in vitro assay methodology for competitive binding of thyroidogenic xenobiotics with thyroxine on human transthyretin and albumin.

Thyroid hormones (THs) are involved in the regulation of many physiological processes in vertebrates. Competition for TH binding sites on serum transport proteins can interfere with delivery of THs to target tissues, and this is a potential mechanism of action of exogenous thyroidogenic substances. To date, detailed accounts of in vitro methods for competitive binding with THs on TH transport proteins (human or wildlife) are sparse. In the limited number of published studies on in vitro radio-labelled TH-TH transport protein interactions, method descriptions were brief and with insufficient details for successful replication. Furthermore, upon review of these methodologies, we identified several opportunities for optimization. The present study addresses the methodological deficiencies and describes, in detail, a fully optimized and validated competitive T4 radio-ligand binding assay with human transthyretin (TTR) and albumin (ALB). •Significant improvements were made over previous methods, including better maintenance of protein stability and enhanced measurement of competition between different ligands.•Sample size was reduced to allow use of small pre-packed size exclusion chromatography columns, which eliminates the rinsing step during the separation procedure.•The assay was parameterized for use with T4 and human TTR and ALB.

Cochlear implants for children with significant residual hearing.

BACKGROUND: Previous research suggests that children with pure-tone averages of greater than 90 dB hearing level and/or open-set sentence perception of less than 30% may derive significant benefit from cochlear implantation. OBJECTIVE: To evaluate postoperative speech perception benefit and bilateral-bimodal benefit for 16 children whose preimplant speech perception scores exceeded conservative candidacy guidelines. STUDY DESIGN: Preimplant and postimplant repeated-measure design. METHODS: Sixteen child subjects who obtained 30% or greater on preimplant open-set sentence material, presented live voice audition alone, were selected for this study. Preimplant pure-tone averages ranged from 73 to 110 dB in the better aided ear. Preimplant and postimplant open-set word and sentence testing was completed in quiet and with competing background noise for separate ear and binaural conditions. RESULTS: Fourteen of 16 subjects had improved speech perception scores across all test materials after implantation. Group means were significantly higher for all test materials. Results in the bimodal-bilateral condition were significantly higher than implant alone for open-set word tests (scored for phonemes) and open-set sentences in quiet. CONCLUSION: The results of this study suggest that, with appropriate counseling and management, some children with significant residual hearing benefit from cochlear implantation, in particular improved speech understanding due to bimodal-bilateral hearing.