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In search of pharmaceuticals with increased effectiveness and reduced toxicity, analogue chemicals came into focus. So far, toxicity and teratogenicity data of drugs and metabolites have usually been collected from mammalian model systems such as mice and rats. However, in an attempt to reduce mammalian testing while maintaining the reliability of toxicity testing of new industrial chemicals and drugs, alternative test methods are being developed. To this end, the potential of the zebrafish (\n                    <jats:italic>Danio rerio<\/jats:italic>\n                    ) embryo to discriminate between valproic acid and 14 analogues was investigated by exposing zebrafish embryos for 120\u00a0h post fertilization in the extended version of the fish embryo acute toxicity test (FET; OECD TG 236), and analyzing liver histology to evaluate the correlation of liver effects and the molecular structure of each compound. Although histological evaluation of zebrafish liver did not identify steatosis as the prominent adverse effect typical in human and mice, the structure\u2013activity relationship (SAR) derived was comparable not only to human HepG2 cells, but also to available in vivo mouse and rat data. Thus, there is evidence that zebrafish embryos might serve as a tool to bridge the gap between subcellular, cell-based systems and vertebrate models.\n                  <\/jats:p>","DOI":"10.1007\/s00204-022-03340-z","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T06:03:01Z","timestamp":1659506581000},"page":"3033-3051","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Potential of the zebrafish (Danio rerio) embryo test to discriminate between chemicals of similar molecular structure\u2014a study with valproic acid and 14 of its analogues"],"prefix":"10.1007","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2365-3330","authenticated-orcid":false,"given":"Katharina","family":"Brotzmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E.","family":"Escher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Braunbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"3340_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s40268-014-0042-z","volume":"14","author":"MA Abdel-Dayem","year":"2014","unstructured":"Abdel-Dayem MA, Elmarakby AA, Abdel-Aziz AA et al (2014) Valproate-induced liver injury: modulation by the omega-3 fatty acid DHA proposes a novel anticonvulsant regimen. 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Preliminary results of this study have been included in: Sylvia E. Escher, Alejandro Aguayo-Orozco, Emilio Benfenati, Annette Bitsch, Thomas Braunbeck, Katharina Brotzmann, Frederic Bois, Bart van der Burg, Jose Castel, Thomas Exner, Domenico Gadaleta, Iain Gardner, Daria Goldmann, Oliver Hatley, Nazanin Golbamaki, Rabea Graepel, Paul Jennings, Alice Limonciel, Anthony Long, Richard Maclennan, Enrico Mombelli, Ulf Norinder, Sankalp Jain, Liliana Santos Capinha, Olivier T. Taboureau, Laia Tolosa, Nanette G. Vrijenhoek, Barbara M.A. van Vugt-Lussenburg, Paul Walker, Bob van de Water, Matthias Wehr, Andrew White, Barbara Zdrazil, Ciar\u00e1n Fisher (2022) Integrate mechanistic evidence from new approach methodologies (NAMs) into a read-across assessment to characterize trends in shared mode of action. Toxicology in Vitro 79 (2022) 105269,\n                      \n                      .","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}