{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:19:46Z","timestamp":1787170786981,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The primary objective of the present study was to examine the influence of early systemic toxicity resulting from copper (Cu) exposure on metamorphic processes in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Xenopus laevis<\/jats:italic>\n                    <\/jats:styled-content>\n                    . A 28\u2010day exposure study with copper, initiated at developmental stage 10, was performed using test concentrations of 3.0, 9.0, 27.2, 82.5, and 250\u2009\u03bcg Cu\/L. The primary endpoints included mortality, developmental stage, embryo\u2010larval malformation, behavioral effects, hindlimb length (HLL), growth (snout\u2010vent length [SVL] and wet body weight), and histopathology. The 28\u2010day LC50 value with 95% confidence intervals was 61.2 (51.4\u201372.9)\u00a0\u03bcg Cu\/L with 250\u2009\u03bcg Cu\/L resulting in complete lethality. Developmental arrest in the 82.5 and delay in the 27.2\u00a0\u03bcg Cu\/L treatments was observed as early as study day 10 continuing throughout the remainder of exposure. SVL\u2010normalized HLL, body weight, and SVL in the 27.2 and 82.5\u00a0\u03bcg Cu\/L treatments were significantly decreased relative to control. At 82.5\u00a0\u03bcg Cu\/L, and thyroid gland size was markedly reduced when compared with controls consistent with the stage of developmental and growth arrest. Concentration\u2010dependent findings in the intestine, liver, gills, eyes, and pharyngeal mucosa were consistent with non\u2010endocrine systemic toxicity. These were prevalent in the 9.0 and 27.2\u00a0\u03bcg Cu\/L treatment groups but were minimally evident or absent in the 82.5\u00a0\u03bcg\/L group, which was attributed to developmental arrest. In conclusion, developmental delay in larvae exposed to 27.2 and 82.5\u00a0\u03bcg Cu\/L was the result of systemic toxicity occurring in early development prior hypothalomo\u2010pituitary\u2010thyroid axis (HPT)\u2010driven metamorphosis and was not indicative of endocrine disruption.\n                  <\/jats:p>","DOI":"10.1002\/jat.4393","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T18:03:46Z","timestamp":1662573826000},"page":"431-445","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Influence of systemic copper toxicity on early development and metamorphosis in\n                    <scp>\n                      <i>Xenopus laevis<\/i>\n                    <\/scp>"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9071-014X","authenticated-orcid":false,"given":"Douglas J.","family":"Fort","sequence":"first","affiliation":[{"name":"Fort Environmental Laboratories, Inc.  Stillwater Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Todhunter","sequence":"additional","affiliation":[{"name":"Fort Environmental Laboratories, Inc.  Stillwater Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Experimental Pathology Laboratories, Inc.  Sterling Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Long","sequence":"additional","affiliation":[{"name":"Regulatory Compliance Limited  Loanhead Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"Poland","sequence":"additional","affiliation":[{"name":"Regulatory Compliance Limited  Loanhead Midlothian UK"},{"name":"Centre for Inflammation Research University of Edinburgh, Queen's Medical Research Institute  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micheal","family":"McGrath","sequence":"additional","affiliation":[{"name":"Necon Technologies Ltd  Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-3969","authenticated-orcid":false,"given":"Stijn","family":"Baken","sequence":"additional","affiliation":[{"name":"European Copper Institute  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Mackie","sequence":"additional","affiliation":[{"name":"Regulatory Compliance Limited  Loanhead Midlothian UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-196-43171A"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-14-167"},{"key":"e_1_2_8_4_1","unstructured":"ASTM. (2019).Standard guide for conducting the frog embryo teratogenesis assay \u2010Xenopus(FETAX). American Society for Testing and Materials (ASTM) E 1439\u201012 (Reapproved 2019)."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0043-1354(82)90171-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/etc.5483"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.03.020"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.9.3820"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11270-017-3548-5"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1897\/06-487R.1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.21081"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/etc.2835"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408440601123545"},{"key":"e_1_2_8_14_1","article-title":"Importance of diet in amphibian metamorphosis\u2010based studies designed to assess the risk of thyroid active substances","author":"Fort D. J.","journal-title":"Journal of Applied Toxicology"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1263(200009\/10)20:5<419::AID-JAT708>3.0.CO;2-A"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.997"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1385\/BTER:77:2:159"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(03)00159-8"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623309335063"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780198717478.003.0005"},{"key":"e_1_2_8_21_1","first-page":"557","article-title":"Endocrine disruptors in amphibians: Potential impacts and the usefulness of amphibian screens for detecting endocrine disrupting compounds","volume":"68","author":"Hayes T. B.","year":"1998","journal-title":"Sci J"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2020.105671"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/etc.1849"},{"key":"e_1_2_8_24_1","first-page":"2261","article-title":"La triiodothyronine: Hormone de la metamorphose des amphibiens","volume":"284","author":"Leloup J.","year":"1977","journal-title":"CR Acad Sci"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2021.112518"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2007.02.011"},{"key":"e_1_2_8_27_1","volume-title":"Normal tables of Xenopus laevis (Daudin)","author":"Nieuwkoop P. D.","year":"1994"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1787\/9789264085275-en"},{"key":"e_1_2_8_29_1","volume-title":"OECD guidelines for the testing of chemicals, Section 2","author":"OECD","year":"2009"},{"key":"e_1_2_8_30_1","volume-title":"OECD guidelines for the testing of chemicals, section 2","author":"OECD","year":"2015"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2013.06.009"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10646-016-1681-3"},{"key":"e_1_2_8_33_1","volume-title":"Amphibian metamorphosis. From morphology to molecular biology","author":"Shi Y. B.","year":"2000"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2011.06.020"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-0072-2_1"},{"key":"e_1_2_8_36_1","unstructured":"USEPA. (2009).OCSPP. 890.1100 amphibian metamorphosis (frog) test guidelines. Washington DC EPA 740\u2010C\u201009\u2010002 http:\/\/www.regulations.gov\/#!documentDetail;D=EPA-HQ-OPPT-2009-0576-0002"},{"key":"e_1_2_8_37_1","unstructured":"USEPA. (2014).Method 6020B\u2014Inductive coupled plasma\u2010mass spectrometry. Methods for Evaluating Solid Wastes SW\u2010846 Final Update III."},{"key":"e_1_2_8_38_1","unstructured":"US Environmental Protection Agency. (2015).Endocrine disruptor screening program test guideline 890.2300: Larval Amphibian Development and Growth Assay (LAGDA). EPA 740\u2010C\u201015\u20100012. Office of Prevention Pesticides and Toxic Substances Washington DC."},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2015.10.023"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408444.2021.1997910"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4393","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.4393","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4393","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:02:35Z","timestamp":1760536955000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,19]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/jat.4393"],"URL":"https:\/\/doi.org\/10.1002\/jat.4393","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,19]]},"assertion":[{"value":"2022-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}