{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:52:17Z","timestamp":1781783537100,"version":"3.54.5"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Research Science of Pharmaceuticals and Medical Devices, Japan Agency of Medical Research and Development","award":["21mk0101133j0003"],"award-info":[{"award-number":["21mk0101133j0003"]}]},{"name":"Research Science of Pharmaceuticals and Medical Devices, Japan Agency of Medical Research and Development","award":["24mk0101239j0003"],"award-info":[{"award-number":["24mk0101239j0003"]}]},{"name":"Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency","award":["JPMEERF25S21230"],"award-info":[{"award-number":["JPMEERF25S21230"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A comprehensive picture of the environmental risks posed by pharmaceuticals in Japan remains unclear, primarily because of the limited availability of toxicity data related to the number of pharmaceuticals prescribed or detected in aquatic environments. To understand the environmental risk, we first compiled toxicity data from the literature, focusing on chronic toxicity. For compounds for which no published information is available, we conducted (sub-)chronic toxicity tests at three trophic levels. We obtained toxicity data, mainly chronic toxicity data, for &amp;gt;75 pharmaceutical compounds. Combining these data with the results of nationwide monitoring surveys of rivers and lakes in Japan, we conducted a comprehensive environmental risk assessment of &amp;gt;75 pharmaceuticals. The results showed that roxithromycin (a macrolide antibiotic) exhibited high toxicity to algae, whereas teprenone (antipeptic ulcer agent), ticlopidine (anticoagulant), and eperisone (muscle relaxant) showed high toxicity to daphnids. Fewer pharmaceuticals have demonstrated similarly high toxicity to fish. Among the selected pharmaceuticals, macrolide antibiotics pose the highest environmental risk, though they present only a moderate risk to algae, with certain compounds exceeding a toxic unit value of 0.1. For daphnids, environmental risks of diverse pharmaceuticals were relatively high but the toxic unit values were at most approximately 0.1, indicating moderate or low risk. The environmental risk to fish was generally lower than that to algae and daphnids. The sum of the toxic units indicated that the highest value for algae exceeded 1. This suggests that pharmaceutical contamination poses a significant risk to the aquatic environment in some locations in Japan.<\/jats:p>","DOI":"10.1093\/etojnl\/vgag080","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:52:47Z","timestamp":1776401567000},"page":"1636-1652","source":"Crossref","is-referenced-by-count":1,"title":["A comprehensive ecological risk assessment of pharmaceuticals in Japan with newly obtained chronic toxicity"],"prefix":"10.1093","volume":"45","author":[{"given":"Yoshikazu","family":"Ninomiya","sequence":"first","affiliation":[{"name":"Department of Natural Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo , Kashiwa, Chiba,","place":["Japan"]},{"name":"Health and Environmental Risk Division, National Institute for Environmental Studies (NIES) , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Oda","sequence":"additional","affiliation":[{"name":"Health and Environmental Risk Division, National Institute for Environmental Studies (NIES) , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruna","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Natural Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo , Kashiwa, Chiba,","place":["Japan"]},{"name":"Health and Environmental Risk Division, National Institute for Environmental Studies (NIES) , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Department of Natural Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo , Kashiwa, Chiba,","place":["Japan"]},{"name":"Health and Environmental Risk Division, National Institute for Environmental Studies (NIES) , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4556-2598","authenticated-orcid":false,"given":"Norihiro","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Environmental Chemistry, National Institute of Health Sciences (NIHS) , Kawasaki, Kanagawa,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Cellular and Molecular Toxicology, National Institute of Health Sciences (NIHS) , Kawasaki, Kanagawa,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Hirose","sequence":"additional","affiliation":[{"name":"National Institute of Health Science Division of Risk Assessment, , Kawasaki, Kanagawa,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3865-8708","authenticated-orcid":false,"given":"Hiroshi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Natural Environmental Studies, Graduate School of Frontier Sciences, The University of Tokyo , Kashiwa, Chiba,","place":["Japan"]},{"name":"Health and Environmental Risk Division, National Institute for Environmental Studies (NIES) , Tsukuba, Ibaraki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"2026061807062087300_vgag080-B1","doi-asserted-by":"publisher","first-page":"2564","DOI":"10.1021\/es2034125","article-title":"Predictive environmental risk assessment of chemical mixtures: A conceptual framework","volume":"46","author":"Backhaus","year":"2012","journal-title":"Environmental Science & 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