{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:25:34Z","timestamp":1787163934359,"version":"build-2736575974"},"reference-count":12,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["42476150"],"award-info":[{"award-number":["42476150"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["42577319"],"award-info":[{"award-number":["42577319"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["W2532031"],"award-info":[{"award-number":["W2532031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:p>A long-standing issue in ecotoxicology is the arbitrarily chosen and ambiguous definition of \u201cenvironmentally relevant\u201d concentrations, which undermines research comparability and hampers risk characterization. Here, we propose a probabilistic framework that anchors exposure levels to percentiles of environmental concentration distributions, defining low (&lt;5th percentile), typical (5th to 95th percentiles), and high (&gt;95th percentile) concentrations, as well as worst-case scenarios (e.g., the 99th percentile) for specific contexts. This framework transforms test concentration selection from a subjective assertion into a statistically justified practice, where each concentration corresponds to an explicit occurrence probability. Using global monitoring data, we demonstrate that environmental concentrations reliably follow cumulative probability distributions, validating the fundamental assumption. Crucially, the framework offers a statistical solution for designing proof-of-relevance and proof-of-concept studies. Collectively, this work provides an empirically grounded, immediately usable template for designing ecotoxicological experiments that bridge environmental monitoring, laboratory testing, and regulatory decision-making.<\/jats:p>","DOI":"10.1073\/pnas.2617990123","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:37:08Z","timestamp":1787161028000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Probabilistically defining environmentally relevant concentrations in ecotoxicology"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1487-861X","authenticated-orcid":false,"given":"Tao","family":"Sun","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034t30j35","id-type":"ROR","asserted-by":"publisher"}],"name":"Shandong Key Laboratory of Coastal Zone Environmental Processes and Ecological Security, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences","place":["Yantai, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-8103","authenticated-orcid":false,"given":"Huifeng","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034t30j35","id-type":"ROR","asserted-by":"publisher"}],"name":"Shandong Key Laboratory of Coastal Zone Environmental Processes and Ecological Security, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences","place":["Yantai, People\u2019s Republic of China"]},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao Marine Science and Technology Center","place":["Qingdao, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5191-4158","authenticated-orcid":false,"given":"Lennart","family":"Weltje","sequence":"additional","affiliation":[{"name":"BASF Agricultural Solutions Deutschland GmbH, Ecotoxicology","place":["Limburgerhof, Germany"]},{"name":"Division of Plant Pathology and Plant Protection, Georg-August-University G\u00f6ttingen","place":["G\u00f6ttingen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-4857","authenticated-orcid":false,"given":"Evgenios","family":"Agathokleous","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y0rxk19","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Ecosystem Carbon Source and Sink, China Meteorological Administration (ECSS-CMA), School of Ecology and Applied Meteorology, Nanjing University of Information Science and Technology","place":["Nanjing, People\u2019s Republic of China"]},{"id":[{"id":"https:\/\/ror.org\/01q8k8p90","id-type":"ROR","asserted-by":"publisher"}],"name":"Climate and Atmosphere Research Center, The Cyprus Institute","place":["Nicosia, Cyprus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Calabrese","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0072zz521","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Environmental Health Sciences, University of Massachusetts","place":["Amherst"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Sumpter","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00dn4t376","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Life Sciences, Brunel University London","place":["Uxbridge, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1606615113"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/es502440s"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.7b04673"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.4c00686"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.5c09003"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41612-020-0121-5"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.6b00608"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1051\/radiopro\/20116728s"},{"key":"e_1_3_4_9_2","unstructured":"U.S. EPA \u201cGuidance for data quality assessment. 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