{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T16:34:20Z","timestamp":1776875660446,"version":"3.51.2"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The embryonic stem cell test (EST) is a validated <jats:italic>in vitro<\/jats:italic> embryotoxicity test; however, as the inhibition of cardiac differentiation alone is used as a differentiation endpoint in the EST, it may not be a useful test to screen embryotoxic chemicals that affect the differentiation of noncardiac tissues. Previously, methylmercury (MeHg), cadmium and arsenic compounds, which are heavy metals that induce developmental neurotoxicity <jats:italic>in vivo<\/jats:italic>, were misclassified as nonembryotoxic with the EST. The aim of this study was to improve the EST to correctly screen such developmental neurotoxicants. We developed a neuronal endpoint (Tuj\u20101 ID<jats:sub>50<\/jats:sub>) using flow cytometry analysis of Tuj\u20101\u2010positive cells to screen developmental neurotoxicants (MeHg, valproic acid, sodium arsenate and sodium arsenite) correctly using an adherent monoculture differentiation method. Using Tuj\u20101 ID<jats:sub>50<\/jats:sub> in the EST instead of cardiac ID<jats:sub>50<\/jats:sub>, all of the tested chemicals were classified as embryotoxic, while the negative controls were correctly classified as nonembryotoxic. To support the validity of Tuj\u20101 ID<jats:sub>50<\/jats:sub>, we compared the results from two experimenters who independently tested MeHg using our modified EST. An additional neuronal endpoint (MAP2 ID<jats:sub>50<\/jats:sub>), obtained by analyzing the relative quantity of MAP2 mRNA, was used to classify the same chemicals. There were no significant differences in the three endpoint values of the two experimenters or in the classification results, except for isoniazid. In conclusion, our results indicate that Tuj\u20101 ID<jats:sub>50<\/jats:sub> can be used as a surrogate endpoint of the traditional EST to screen developmental neurotoxicants correctly and it can also be applied to other chemicals. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1747","type":"journal-article","created":{"date-parts":[[2011,12,2]],"date-time":"2011-12-02T10:28:12Z","timestamp":1322821692000},"page":"617-626","source":"Crossref","is-referenced-by-count":28,"title":["Embryotoxicity assessment of developmental neurotoxicants using a neuronal endpoint in the embryonic stem cell test"],"prefix":"10.1002","volume":"32","author":[{"given":"Dae Hyun","family":"Baek","sequence":"first","affiliation":[{"name":"Center for Drug Development Assistance National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration  Cheongwon\u2010gun Chungcheongbuk\u2010do 363\u2010951 South Korea"},{"name":"Laboratory of Veterinary Pharmacology, College of Veterinary Medicine Seoul National University  Seoul 151\u2010742 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae 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