{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:32Z","timestamp":1792785872199,"version":"4.5.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","funder":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, Chemical Safety for Sustainability National Research","id":[{"id":"https:\/\/ror.org\/03tns0030","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>High throughput (HTP) assays using aquatic species are being developed in response to the large number of chemicals in or entering commerce with little aquatic toxicological data. Transcriptomic points of departure (tPODs) coupled to HTP assays have shown promise in efficiently assessing possible toxicity of chemicals. With thousands of identified per- and polyfluoroalkyl substances (PFAS), such strategies are required to assess their potential hazard to aquatic species. This study investigated the utility of an HTP transcriptomic assay with an aquatic insect (Chironomus dilutus) to assess the toxicity of 22 PFAS. Larval C. dilutus were exposed for 24 hr in 96-well microplates to a concentration series of each PFAS. Following exposure, tPODs were calculated from the transcriptomic data. The tPODs ranged from 3\u2009\u00b5g\/L for 6:2 fluorotelomer sulfonic acid to 1,602\u2009\u00b5g\/L for perfluoropentanoic acid. These values were compared with tPODs previously derived for fathead minnow (Pimephales promelas), Daphnia magna, a microalga (Raphidocelis subcapitata), and from mammalian cell culture HTP assays. In addition, C. dilutus tPODs were compared with published surface water concentrations, which were typically orders of magnitude lower than the tPOD. The C. dilutus HTP assay showed promise as a new approach methodology to assess the toxicity of chemicals, such as PFAS, as part of a tiered hazard evaluation strategy.<\/jats:p>","DOI":"10.1093\/etojnl\/vgag244","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:14:41Z","timestamp":1788855281000},"source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic points of departure from the aquatic insect\n                    <i>Chironomus dilutus<\/i>\n                    for 22 PFAS and their use in chemical hazard screening"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-5633","authenticated-orcid":false,"given":"Kevin M","family":"Flynn","sequence":"first","affiliation":[{"name":"Office of Chemical Safety and Pollution Prevention, Office of Mission Critical Operations, Risk Assessment Support Division, U. S. Environmental Protection Agency , Duluth, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra","family":"Bush","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education (ORISE) Research Participant, U. S. Environmental Protection Agency , Duluth, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Cavallin","sequence":"additional","affiliation":[{"name":"Office of Chemical Safety and Pollution Prevention, Office of Mission Critical Operations, Risk Assessment Support Division, U. S. Environmental Protection Agency , Duluth, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Kasparek","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education (ORISE) Research Participant, U. S. Environmental Protection Agency , Duluth, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schumann","sequence":"additional","affiliation":[{"name":"Zebrafishlab, Veterinary Physiology and Biochemistry, University of Antwerp , Wilrijk,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L","family":"Villeneuve","sequence":"additional","affiliation":[{"name":"Office of Chemical Safety and Pollution Prevention, Office of Mission Critical Operations, Risk Assessment Support Division, U. S. Environmental Protection Agency , Duluth, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2026093007515313900_vgag244-B1","author":"3M Company","year":"2022"},{"key":"2026093007515313900_vgag244-B2","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/etc.4869","article-title":"Assessing the ecological risks of per- and polyfluoroalkyl substances: Current state-of-the science and a proposed path forward","volume":"40","author":"Ankley","year":"2021","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B3","doi-asserted-by":"publisher","author":"Basu","year":"2025","DOI":"10.1101\/2023.07.07.547968"},{"key":"2026093007515313900_vgag244-B4","doi-asserted-by":"publisher","DOI":"10.23645\/epacomptox.25365496","volume-title":"Standard methods for development of EPA transcriptomic assessment products (ETAPs)","author":"Brennan","year":"2024"},{"key":"2026093007515313900_vgag244-B5","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1021\/acs.chemrestox.2c00344","article-title":"Evaluation of per- and polyfluoroalkyl substances (PFAS) in vitro toxicity testing for developmental neurotoxicity","volume":"36","author":"Carstens","year":"2023","journal-title":"Chemical Research in Toxicology"},{"key":"2026093007515313900_vgag244-B6","doi-asserted-by":"publisher","first-page":"e107","DOI":"10.1002\/imt2.107","article-title":"Ultrafast one-pass FASTQ data preprocessing, quality control, and deduplication using Fastp","volume":"2","author":"Chen","year":"2023","journal-title":"iMeta"},{"key":"2026093007515313900_vgag244-B7","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"2026093007515313900_vgag244-B8","doi-asserted-by":"publisher","first-page":"1374791","DOI":"10.3389\/fgene.2024.1374791","article-title":"Transcriptomic point of departure determination: A comparison of distribution-based and gene set-based approaches","volume":"15","author":"Costa","year":"2024","journal-title":"Frontiers in Genetics"},{"key":"2026093007515313900_vgag244-B9","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1002\/etc.4893","article-title":"Per- and polyfluoroalkyl substances (PFAS) in surface water near US air force bases: Prioritizing individual chemicals and mixtures for toxicity testing and risk assessment","volume":"40","author":"East","year":"2021","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B10","author":"European Chemicals Agency","year":"2026"},{"key":"2026093007515313900_vgag244-B11","doi-asserted-by":"publisher","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"2026093007515313900_vgag244-B12","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1007\/s00244-024-01064-y","article-title":"Comparing transcriptomic points of departure to apical effect concentrations for larval fathead minnow exposed to chemicals with four different modes of action","volume":"86","author":"Flynn","year":"2024","journal-title":"Archives of Environmental Contamination and Toxicology"},{"key":"2026093007515313900_vgag244-B13","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1093\/etojnl\/vgaf022","article-title":"Transcriptomic response of an algal species (Raphidocelis subcapitata) exposed to 22 per- and polyfluoroalkyl substances","volume":"44","author":"Flynn","year":"2025","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B14","first-page":"45","article-title":"An overview of toxicogenomics","volume":"4","author":"Hamadeh","year":"2002","journal-title":"Current Issues Molecular Biology"},{"key":"2026093007515313900_vgag244-B15","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/toxsci\/kfab009","article-title":"High-throughput transcriptomics platform for screening environmental chemicals","volume":"181","author":"Harrill","year":"2021","journal-title":"Toxicological Sciences"},{"key":"2026093007515313900_vgag244-B16","doi-asserted-by":"publisher","first-page":"152789","DOI":"10.1016\/j.tox.2021.152789","article-title":"Bioactivity profiling of per- and polyfluoroalkyl substances (PFAS) identifies potential toxicity pathways related to molecular structure","volume":"457","author":"Houck","year":"2021","journal-title":"Toxicology"},{"key":"2026093007515313900_vgag244-B17","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1002\/etc.5147","article-title":"Perfluorooctane sulfonate in US ambient surface waters: A review of occurrence in aquatic environments and comparison to global concentrations","volume":"40","author":"Jarvis","year":"2021","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B18","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1093\/toxsci\/kfac097","article-title":"A transformative vision for an omics-based regulatory chemical testing paradigm","volume":"190","author":"Johnson","year":"2022","journal-title":"Toxicological Sciences"},{"key":"2026093007515313900_vgag244-B19","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1002\/etc.5784","article-title":"Sublethal toxicity of 17 per- and polyfluoroalkyl substances with diverse structures to Ceriodaphnia dubia, Hyalella azteca, and Chironomus dilutus","volume":"43","author":"Kadlec","year":"2024","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B20","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1021\/tx3000939","article-title":"Update on EPA\u2019s ToxCast program: Providing high throughput decision support tools for chemical risk management","volume":"25","author":"Kavlock","year":"2012","journal-title":"Chemical Research in Toxicology"},{"key":"2026093007515313900_vgag244-B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00204-019-02613-4","article-title":"Toxicity testing in the 21st century: Progress in the past decade and future perspectives","volume":"94","author":"Krewski","year":"2020","journal-title":"Archives of Toxicology"},{"key":"2026093007515313900_vgag244-B22","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nature Methods"},{"key":"2026093007515313900_vgag244-B23","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1093\/etojnl\/vgaf077","article-title":"Per- and polyfluoroalkyl substances in surface water and sediment in Great Lakes tributaries and relations with watershed attributes","volume":"44","author":"Loken","year":"2025","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B24","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1002\/etc.4392","article-title":"Effects of perfluoralkyl substances on a multigenerational scale: A case study with Chironomus riparius (Diptera, Chironomidae)","volume":"38","author":"Marziali","year":"2019","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B25","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1002\/etc.5066","article-title":"Toxicological response of Chironomus dilutus in single-chemical and binary mixture exposure experiments with 6 perfluoralkyl substances","volume":"40","author":"McCarthy","year":"2021","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B26","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1002\/etc.5395","article-title":"Transcriptomic points of departure calculated from rainbow trout gill, liver, and gut cell lines exposed to methylmercury and fluoxetine","volume":"41","author":"Mittal","year":"2022","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B27","doi-asserted-by":"crossref","DOI":"10.22427\/NTP-RR-5","volume-title":"National Toxicology Program approach to genomic dose-response modeling","author":"National Toxicology Program","year":"2018"},{"key":"2026093007515313900_vgag244-B28","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1002\/etc.5324","article-title":"The ECOTOXicology Knowledgebase: A curated database of ecologically relevant toxicity tests to support environmental research and risk assessment","volume":"41","author":"Olker","year":"2022","journal-title":"Environmental Toxicology and Chemistry"},{"issue":"141","key":"2026093007515313900_vgag244-B29","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/s0378-4274(02)00500-3","article-title":"Toxicogenomics: Challenges and opportunities","volume":"140","author":"Orphanides","year":"2003","journal-title":"Toxicology Letters"},{"key":"2026093007515313900_vgag244-B30","doi-asserted-by":"publisher","first-page":"114634","DOI":"10.1016\/j.taap.2019.114634","article-title":"Transcriptomic point-of-departure from short-term exposure studies are protective of chronic effects for fish exposed to estrogenic chemicals","volume":"378","author":"Page-Lariviere","year":"2019","journal-title":"Toxicology and Applied Pharmacology"},{"key":"2026093007515313900_vgag244-B31","doi-asserted-by":"publisher","first-page":"105002","DOI":"10.1289\/EHP6500","article-title":"Drivers of and obstacles to the adoption of toxicogenomics for chemical risk assessment: Insights from social science perspectives","volume":"128","author":"Pain","year":"2020","journal-title":"Environmental Health Perspectives"},{"key":"2026093007515313900_vgag244-B32","doi-asserted-by":"publisher","first-page":"100250","DOI":"10.1016\/j.comtox.2022.100250","article-title":"Towards reproducible structure-based chemical categories for PFAS to inform and evaluate toxicity and toxicokinetic testing","volume":"24","author":"Patlewicz","year":"2022","journal-title":"Computational Toxicology"},{"key":"2026093007515313900_vgag244-B33","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nature Methods"},{"key":"2026093007515313900_vgag244-B34","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1093\/bioinformatics\/bty878","article-title":"BMDExpress 2: Enhanced transcriptomic dose-response analysis workflow","volume":"35","author":"Phillips","year":"2019","journal-title":"Bioinformatics"},{"key":"2026093007515313900_vgag244-B35","doi-asserted-by":"publisher","first-page":"1194895","DOI":"10.3389\/ftox.2023.1194895","article-title":"From vision toward best practices: Evaluating in vitro transcriptomic points of departure for application in risk assessment using a uniform workflow","volume":"5","author":"Reardon","year":"2023","journal-title":"Frontiers in Toxicology"},{"key":"2026093007515313900_vgag244-B36","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1021\/acs.est.3c07525","article-title":"High-throughput transcriptomics of water extracts detects reductions in biological activity with water treatment processes","volume":"58","author":"Rogers","year":"2024","journal-title":"Environmental Science & Technology"},{"key":"2026093007515313900_vgag244-B37","doi-asserted-by":"publisher","first-page":"151535","DOI":"10.1016\/j.scitotenv.2021.151535","article-title":"Global occurrence and probabilistic environmental health hazard assessment of per- and polyfluoroalkyl substances (PFASs) in groundwater and surface waters","volume":"816","author":"Sims","year":"2022","journal-title":"Science of the Total Environment"},{"key":"2026093007515313900_vgag244-B38","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1021\/acs.chemrestox.3c00003","article-title":"Plasma protein binding evaluations of per- and polyfluoroalkyl substances for category-based toxicokinetic assessment","volume":"36","author":"Smeltz","year":"2023","journal-title":"Chemical Research in Toxicology"},{"key":"2026093007515313900_vgag244-B39","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1093\/toxsci\/kfm092","article-title":"A method to integrate benchmark dose estimates with genomic data to assess the functional effects of chemical exposure","volume":"98","author":"Thomas","year":"2007","journal-title":"Toxicological Sciences"},{"key":"2026093007515313900_vgag244-B40","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1093\/toxsci\/kfz058","article-title":"The next generation blueprint of computational toxicology at the US Environmental Protection Agency","volume":"169","author":"Thomas","year":"2019","journal-title":"Toxicological Sciences"},{"key":"2026093007515313900_vgag244-B41","volume-title":"Methods for measuring the toxicity and bioaccumulation of sediment-associated contaminants with freshwater invertebrates","author":"U. S. Environmental Protection Agency","year":"2000"},{"key":"2026093007515313900_vgag244-B42","author":"U. S. Environmental Protection Agency","year":"2016"},{"key":"2026093007515313900_vgag244-B43","volume-title":"PFAS strategic roadmap: EPA commitments to action 2021-2024","author":"U. S. Environmental Protection Agency","year":"2021"},{"key":"2026093007515313900_vgag244-B44","author":"U. S. Environmental Protection Agency","year":"2023"},{"key":"2026093007515313900_vgag244-B45","author":"U. S. Environmental Protection Agency","year":"2024"},{"key":"2026093007515313900_vgag244-B46","doi-asserted-by":"publisher","first-page":"100099","DOI":"10.1016\/j.crtox.2022.100099","article-title":"Pilot testing and optimization of a larval fathead minnow high throughput transcriptomics assay","volume":"4","author":"Villeneuve","year":"2023","journal-title":"Current Research in Toxicology"},{"key":"2026093007515313900_vgag244-B47","doi-asserted-by":"publisher","first-page":"2470","DOI":"10.1002\/etc.5838","article-title":"Transcriptomics-based points of departure for Daphnia magna exposed to 18 per- and polyfluoroalkyl substances","volume":"44","author":"Villeneuve","year":"2024","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B48","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1002\/etc.5825","article-title":"Derivation of transcriptomics-based points of departure for twenty per- or polyfluoroalkyl substances (PFAS) using a larval fathead minnow (Pimephales promelas) reduced transcriptome assay","volume":"44","author":"Villeneuve","year":"2024","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2026093007515313900_vgag244-B49","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1038\/nrg1493","article-title":"Toxicogenomics and systems toxicology: Aims and prospects","volume":"5","author":"Waters","year":"2004","journal-title":"Nature Reviews. Genetics"},{"key":"2026093007515313900_vgag244-B50","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1897\/IEAM_2009-069.1","article-title":"The chironomid acute toxicity test: Development of a new test system","volume":"6","author":"Weltje","year":"2010","journal-title":"Integrated Environmental Assessment and Management"},{"key":"2026093007515313900_vgag244-B51","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13321-017-0247-6","article-title":"The CompTox chemistry dashboard: A community data resource for environmental chemistry","volume":"9","author":"Williams","year":"2017","journal-title":"Journal of Cheminformatics"},{"key":"2026093007515313900_vgag244-B52","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1186\/1471-2164-8-387","article-title":"BMDExpress: A software tool for the benchmark dose analyses of genomic data","volume":"8","author":"Yang","year":"2007","journal-title":"BMC Genomics"},{"key":"2026093007515313900_vgag244-B53","doi-asserted-by":"publisher","first-page":"125541","DOI":"10.1016\/j.chemosphere.2019.125541","article-title":"Development of the transcriptome for a sediment ecotoxicological model species, Chironomus dilutus","volume":"244","author":"Zhang","year":"2020","journal-title":"Chemosphere"}],"container-title":["Environmental Toxicology and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/etc\/advance-article-pdf\/doi\/10.1093\/etojnl\/vgag244\/70989203\/vgag244.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/etc\/advance-article-pdf\/doi\/10.1093\/etojnl\/vgag244\/70989203\/vgag244.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:51:59Z","timestamp":1790769119000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/etc\/advance-article\/doi\/10.1093\/etojnl\/vgag244\/8787747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":53,"URL":"https:\/\/doi.org\/10.1093\/etojnl\/vgag244","relation":{},"ISSN":["0730-7268","1552-8618"],"issn-type":[{"value":"0730-7268","type":"print"},{"value":"1552-8618","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"article-number":"vgag244"}}