{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:35Z","timestamp":1786978055238,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T00:00:00Z","timestamp":1542672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Diclofenac sodium, a non\u2010steroidal anti\u2010inflammatory drug widely used in both human and veterinary medicine, has been detected in aquatic environments; therefore, its ecotoxicological effects on aquatic organisms need to be clarified. Recently, toxicity testing using zebrafish (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Danio rerio<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) embryos has been recommended from the point of view of animal welfare; therefore, we investigated the suitability of using sub\u2010lethal endpoints observed during embryogenesis for predicting lethal effects in early life stage zebrafish exposed to diclofenac sodium. After exposure to diclofenac sodium (0.4\u20107.0\u00a0mg\/L) from 2\u00a0hours post\u2010fertilization to 30\u00a0days post\u2010hatching, abnormal embryogenesis, characterized by the presence of edema and body curvature, was observed in the 7.0\u00a0mg\/L exposure group but not in any other groups including controls. The body curvature was found to be the result of abnormal development of the spine. All abnormal embryos hatched without delay, but died within 1\u00a0week after hatching, suggesting that the combination of the sub\u2010lethal endpoints of edema and abnormal development of the spine during embryogenesis may predict lethal effects in early life stage zebrafish exposed to diclofenac sodium. Further investigations to verify these findings are needed. The value of the no observed effect concentrations for the embryogenesis, survival and growth endpoints were 3.5, 1.8 and &gt;3.5\u00a0mg\/L, respectively.\n                  <\/jats:p>","DOI":"10.1002\/jat.3752","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T21:40:51Z","timestamp":1542750051000},"page":"622-629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The non\u2010steroidal anti\u2010inflammatory drug diclofenac sodium induces abnormal embryogenesis and delayed lethal effects in early life stage zebrafish (\n                    <scp>\n                      <i>Danio rerio<\/i>\n                    <\/scp>\n                    )"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4558-8624","authenticated-orcid":false,"given":"Yoshifumi","family":"Horie","sequence":"first","affiliation":[{"name":"Faculty of Bioresource Sciences Akita Prefectural University  241\u2010438 Kaidobata\u2010Nishi, Nakano Simoshinjo Akita 010\u20100195 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Center for Health and Environmental Risk Research National Institute for Environmental Studies  16\u20102 Onogawa, Tsukuba Ibaraki 305\u20108506 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayano","family":"Yagi","sequence":"additional","affiliation":[{"name":"Center for Health and Environmental Risk Research National Institute for Environmental Studies  16\u20102 Onogawa, Tsukuba Ibaraki 305\u20108506 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Shintaku","sequence":"additional","affiliation":[{"name":"Center for Health and Environmental Risk Research National Institute for Environmental Studies  16\u20102 Onogawa, Tsukuba Ibaraki 305\u20108506 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taisen","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Graduate School of Nanobioscience Yokohama City University  22\u20102 Seto, Kanazawa\u2010ku Yokohama 236\u20100027 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihisa","family":"Tatarazako","sequence":"additional","affiliation":[{"name":"Graduate School of Agriculture Ehime University  Tarumi 3\u20105\u20107 Matsuyama 790\u20108566 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10646-015-1597-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/etc.3339"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.23278"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2012.04.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-014-3814-7"},{"key":"e_1_2_8_7_1","first-page":"1","article-title":"Human pharmaceuticals in the aquatic environment: a review of recent toxicological studies and considerations for toxicity testing","volume":"218","author":"Brausch J. 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