EcoToxChip: A next‐generation toxicogenomics tool for chemical prioritization and environmental management

Environmental Toxicology and Chemistry, Год журнала: 2019, Номер 38(2), С. 279 - 288

Опубликована: Янв. 29, 2019

Chemical contamination of natural ecosystems is regarded as one our planet's greatest threats (Landrigan et al. 2018).Contaminant-related phenomena such malformed frogs, fish with tumors, and dwindling bird populations increasingly fuel societal concerns.Legislation in North America Europe mandates the assessment reduction risk for thousands commercially important chemical substances used by society released into environment.For example, large-scale efforts Chemicals Management Plan Canada, European Union's Registration, Evaluation, Authorisation Restriction (REACH) program, US Environmental Protection Agency's (USEPA's) ToxCast program under Toxic Substances Control Act (1976) were implemented to address legislative obligations identify, prioritize, take action on chemicals found be harmful.However, these regulatory programs face significant challenges.The number which toxicity data are required tremendous backlogged (e.g., 23 000 initially Canada; 85 United States; upward 101 Union) continues grow approximately 500 1000 new each year.In addition, regulations Canada's Wastewater Systems Effluent Regulations (section 36, Fisheries Act), National Pollutant Discharge Elimination System, Water Framework Directive (2000/60/EC) mandate monitoring municipal industrial effluents regard their potential impacts aquatic ecosystem health.These require testing complex environmental samples water, effluents, sediments) compliance;

Язык: Английский

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Effects of Polar Bear and Killer Whale Derived Contaminant Cocktails on Marine Mammal Immunity

Environmental Science & Technology, Год журнала: 2017, Номер 51(19), С. 11431 - 11439

Опубликована: Сен. 6, 2017

Most controlled toxicity studies use single chemical exposures that do not represent the real world situation of complex mixtures known and unknown natural anthropogenic substances. In present study, contaminant cocktails derived from blubber polar bears (PB; Ursus maritimus) killer whales (KW; Orcinus orca) were used for in vitro concentration-response experiments with PB, cetacean seal spp. immune cells to evaluate effect realistic on various functions. Cytotoxic effects PB cocktail occurred at lower concentrations than KW (1 vs 16 μg/mL), likely due differences profiles adipose each species. Similarly, significant reduction lymphocyte proliferation much (EC50: 0.94 6.06 μg/mL; P < 0.01), whereas caused a faster decline (slope: 2.9 1.7; = 0.04). Only modulated (NK) cell activity neutrophil monocyte phagocytosis concentration- species-dependent manner. No clear sensitivity emerged when comparing cetaceans, seals PB. Our results showing levels relative compounds suggest previous risk assessments underestimate exposure immunity. using blubber-derived add realism confirm immunotoxic marine mammals face environmental contaminants.

Язык: Английский

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Why do we monitor? Using seabird eggs to track trends in Arctic environmental contamination

Environmental Reviews, Год журнала: 2021, Номер 30(2), С. 245 - 267

Опубликована: Дек. 7, 2021

Contaminant levels and trends have been monitored in the eggs of seabirds from Canadian Arctic since 1975. Nearly 50 years monitoring provided key information regarding temporal spatial variation various contaminant classes different seabird species. However, previous work has primarily assessed individual or related isolation. There is therefore a need to collectively consider all contaminants determine where successful, find areas for improvement, identify opportunities future research. In this review, we evaluated data major legacy emerging concern five species three High Low colonies Canada. We review history Canada’s egg program discuss how efforts changed over time; summarize temporal, spatial, interspecies variations contamination important knowledge gaps; and, directions ecotoxicology research using Ultimately, paper provides high-level overview underscores importance long-term continued

Язык: Английский

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Use of a Novel Double-Crested Cormorant ToxChip PCR Array and the EROD Assay to Determine Effects of Environmental Contaminants in Primary Hepatocytes

Environmental Science & Technology, Год журнала: 2016, Номер 50(6), С. 3265 - 3274

Опубликована: Фев. 19, 2016

In vitro screening tools and 'omics methods are increasingly being incorporated into toxicity studies to determine mechanistic effects of chemicals mixtures. To date, the majority these have been conducted with well-characterized laboratory animal models. present study, well-established developed for chicken embryonic hepatocyte (CEH) were extended a wild avian species, double-crested cormorant (DCCO; Phalacrocorax auritus), in order compare several environmental contaminants on cytotoxicity, ethoxyresorufin O-deethylase (EROD) activity, mRNA expression. Five organic flame retardants one plasticizer decreased viability similar manner that observed previous CEH. EROD activity was induced concentration-dependent following exposure two dioxin-like calculated EC50 values concordant domestic species from sensitivity categories. Transcriptomic determined using novel DCCO PCR array, which designed, constructed validated our based commercially available array. The array has 27 target genes covering wide range pathways. Gene profiles variable among 10 screened; however, good directional concordance regard results previously obtained Overall, application (i.e., CEH array) demonstrated portability techniques an indicator ecological relevance.

Язык: Английский

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Extracts of Passive Samplers Deployed in Variably Contaminated Wetlands in the Athabasca Oil Sands Region Elicit Biochemical and Transcriptomic Effects in Avian Hepatocytes

Environmental Science & Technology, Год журнала: 2019, Номер 53(15), С. 9192 - 9202

Опубликована: Июль 5, 2019

Recent contaminant monitoring in boreal wetlands situated Alberta's Athabasca oil sands region revealed increased concentrations of polycyclic aromatic compounds (PACs) passive sampling devices deployed close to bitumen surface mining operations. In this study, graded semipermeable membrane device (SPMD) extracts, collected from 4 with variable burdens PACs, were administered chicken and double-crested cormorant (DCCO) embryonic hepatocytes determine effects on 7-ethoxyresorufin-O-deethylase (EROD) activity mRNA expression. Concentrations composition PACs detected SPMDs varied among sites, the proportion alkyl was greater than parent at all sites. ΣPACs highest within 10 km (near-site wetland [5930 ng SPMD-1]) compared those ∼50 south (far-site [689 SPMD-1]). Measures EROD Cyp1a4 expression allowed ranking sites based aryl hydrocarbon receptor-mediated end points; induction near-site wetland. ToxChip PCR arrays (one one DCCO) provided a more exhaustive transcriptomic evaluation across multiple toxicological pathways following exposure SPMD extracts. Study greatest PAC had most genes altered (12-15/43 genes). Exposure avian extracts variably contaminated highlighted traditional PAC-related toxicity as well other novel mechanisms action. A combination techniques high-throughput shows promise terms identifying hotspots chemical concern natural environment.

Язык: Английский

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Prioritization of 10 organic flame retardants using an avian hepatocyte toxicogenomic assay

Environmental Toxicology and Chemistry, Год журнала: 2018, Номер 37(12), С. 3134 - 3144

Опубликована: Авг. 22, 2018

Abstract As the number of chemicals developed and used by industry increases, inherent limitations traditional toxicology approaches become an unavoidable issue. To help meet demand for toxicity evaluation, new methods, such as high‐throughput screening, are currently being to permit rapid determination toxic, molecular, and/or biochemical effects a wide range chemicals. In present study, we demonstrate utility avian in vitro toxicogenomics screening approach determine cytotoxic transcriptomic 10 organic flame retardants (OFRs) international priority ecological risk evaluation prioritize inform future toxicological studies. Hepatocytes from 2 species, chicken double‐crested cormorant, were prepared exposed 24 h various concentrations (0–300 μM) following OFRs: Chemical Abstracts Service registration numbers 29761‐21‐5, 56803‐37‐3 ( p ‐tert‐butylphenyl diphenyl phosphate [BPDP]), 65652‐41‐7, 68937‐41‐7 (phenol, isopropylated, [3:1] [IPPP]), 95906‐11‐9, 19186‐97‐1, 26040‐51‐7, 35948‐25‐5, 21850‐44‐2, 25713‐60‐4. Cell viability, 7‐ethoxyresorufin‐ O ‐deethylase assay, analysis using species‐specific ToxChip polymerase chain reaction arrays performed evaluate effect these OFRs. Of OFRs assessed, BPDP IPPP elicited strongest responses both cormorant hepatocytes therefore recommended candidates further wildlife investigations. Environ Toxicol Chem 2018;37:3134–3144. © 2018 Crown right Canada. Published Wiley Periodicals Inc. on behalf SETAC.

Язык: Английский

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ToxChip PCR Arrays for Two Arctic-Breeding Seabirds: Applications for Regional Environmental Assessments

Environmental Science & Technology, Год журнала: 2021, Номер 55(11), С. 7521 - 7530

Опубликована: Май 13, 2021

Increasing pollution in the Arctic poses challenges terms of geographical and ecological monitoring. The Baffin Bay-Davis Strait (BBDS) region Canadian Archipelago is particular concern due to potential for increased shipping traffic oil exploration. However, data on background contaminants associated with exploration/spills/natural seeps (e.g., polycyclic aromatic compounds [PAC]) measures effects birds are limited. We developed a toxicogenomics approach investigate gene expression profiles two Arctic-breeding seabirds, thick-billed murre (Uria lomvia) black guillemot (Cepphus grylle), which will aid effects-based monitoring efforts. Chemical burdens (53 PACs 5 trace elements) transcriptomic (31 genes using ToxChip PCR array) were examined liver tissues (n = 30) each species collected from Qaqulluit Akpait National Wildlife Areas BBDS region. While chemical demonstrated low variability across individuals species, signatures able distinguish guillemots distinct colonies. This provides benchmark seabirds promising future efforts strategic environmental assessments this sensitive ecosystem areas elsewhere circumpolar that undergoing change.

Язык: Английский

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Athabasca Oil Sands Petcoke Extract Elicits Biochemical and Transcriptomic Effects in Avian Hepatocytes

Environmental Science & Technology, Год журнала: 2017, Номер 51(10), С. 5783 - 5792

Опубликована: Апрель 28, 2017

Petroleum coke or "petcoke" is a granular carbonaceous material produced during the upgrading of heavy crude oils, including bitumen. Petcoke dust was recently reported as an environmental contaminant in Athabasca oil sands region, but ecotoxicological hazards posed by this complex bitumen-derived material-including those to avian species-have not been characterized. In study, solvent extracts (x) delayed and fluid petcoke (xDP xFP) were prepared dissolved dimethyl sulfoxide. A water-accommodated fraction (waDP) also prepared. Graded concentrations xDP, xFP, waDP administered chicken double-crested cormorant hepatocytes determine effects on 7-ethoxyresorufin-O-deethylase (EROD) activity, porphyrin accumulation, mRNA expression. Polycyclic aromatic compounds (PACs) characterized, had total PAC 93 000, 270, 5.3 ng/mL. The rank order biochemical transcriptomic responses xDP > xFP (e.g., EROD EC50s lower for compared waDP). 22, 18, 4 genes altered following exposure highest waDP, respectively, using PCR array comprising 27 AhR-related genes. To provide more exhaustive coverage potential toxicity pathways being impacted, two ToxChip arrays-chicken cormorant-were utilized, expression than xFP. Traditional PAC-related novel mechanisms action identified species extract exposure. Extrapolation real-world scenarios must consider bioavailability extracted PACs exposed organisms.

Язык: Английский

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Sunlight Irradiation of Highly Brominated Polyphenyl Ethers Generates Polybenzofuran Products That Alter Dioxin-responsive mRNA Expression in Chicken Hepatocytes

Environmental Science & Technology, Год журнала: 2016, Номер 50(5), С. 2318 - 2327

Опубликована: Фев. 8, 2016

We report on two highly brominated polyphenyl ether flame retardants, tetradecabromo-1,4- diphenoxybenzene (TeDB-DiPhOBz) and 2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl (BDE-209), that formed photolytic degradation products in tetrahydrofuran (THF)/hexane solvent after 21 days of natural sunlight irradiation (SI). These SI-TeDB-DiPhOBz SI-BDE-209 included the numerous polybrominated homologue groups polybenzofurans dibenzofurans, respectively. Formation similar polybenzofuran dibenzofuran was also observed following a 3 month exposure solid powder forms TeDB-DiPhOBz BDE-209 to SI. resulting product mixtures were administered chicken embryonic hepatocytes (CEH) determine effects mRNA expression levels 27 dioxin-responsive genes. For solvent-based SI study, equivalent concentrations 1 or 25 μM 10 resulted gene profiles those most potent dioxin-like compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin. In addition, concentration-dependent induction CYP1A4 CYP1A5 SI-BDE-209. Based ECthreshold values for CYP1A4/5 expression, relative potency (ReP) × 10–6 10–5 SI-BDE-209, The mixture significantly induced CEH. Our findings clearly show environmental stability BDE-209, possibly other ethers, is great concern from toxicity perspective.

Язык: Английский

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Development and Initial Testing of EcoToxChip, a Novel Toxicogenomics Tool for Environmental Management and Chemical Risk Assessment

Environmental Toxicology and Chemistry, Год журнала: 2023, Номер 42(8), С. 1763 - 1771

Опубликована: Май 19, 2023

Abstract New approach methods (NAMs) are increasingly important to help accelerate the pace of ecological risk assessment and offer more ethical, affordable, efficient alternatives traditional toxicity tests. In present study, we describe development, technical characterization, initial testing a toxicogenomics tool, EcoToxChip (384-well quantitative polymerase chain reaction [qPCR] array), support chemical management environmental monitoring for three laboratory model species—fathead minnow (Pimephales promelas), African clawed frog (Xenopus laevis), Japanese quail (Coturnix japonica). Chip design, including gene selection, was informed by diverse end-user group quality control metrics (e.g., primer assay, reverse transcription, PCR efficiency) performed well based on priori established criteria. Correlation with RNA sequencing (seq) data provided additional confidence in this novel tool. Although study represents an only 24 EcoToxChips each species, results provide increased robustness/reproducibility evaluating perturbations expression associated exposure thus, NAM, combined early-life stage testing, could augment current efforts prioritization management. Environ Toxicol Chem 2023;42:1763–1771. © 2023 SETAC

Язык: Английский

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