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A potential new testing paradigm involves deriving a POD from a comprehensive analysis of molecular\u2010level change. Here, the rat ketoconazole endocrine\u2010mediated developmental toxicity model was used to test the hypothesis that maternal epigenomic (miRNA) and transcriptomic (mRNA) PODs are similar to fetal apical endpoint PODs. Sprague\u2013Dawley rats were exposed from gestation day (GD) 6\u201321 to 0, 0.063, 0.2, 0.63, 2, 6.3, 20, or 40\u2009mg\/kg\/day ketoconazole. Dam systemic, liver, and placenta PODs, along with GD 21 fetal resorption, body weight, and skeletal apical PODs were derived using BMDS software. GD 21 dam liver and placenta miRNA and mRNA PODs were obtained using three methods: a novel individual molecule POD accumulation method, a first mode method, and a gene set method. Dam apical POD values ranged from 2.0 to 38.6\u00a0mg\/kg\/day; the lowest value was for placenta histopathology. Fetal apical POD values were 10.9\u201320.3\u00a0mg\/kg\/day; the lowest value was for fetal resorption. Dam liver miRNA and mRNA POD values were 0.34\u20130.69\u2009mg\/kg\/day, and placenta miRNA and mRNA POD values were 2.53\u20136.83\u2009mg\/kg\/day. Epigenomic and transcriptomic POD values were similar across liver and placenta. Deriving a molecular POD from dam liver or placenta was protective of a fetal apical POD. These data support the conclusion that a molecular POD can be used to estimate, or be protective of, a developmental toxicity apical POD.<\/jats:p>","DOI":"10.1002\/bdr2.2046","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T11:12:34Z","timestamp":1653131554000},"page":"559-576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A<scp>microRNA<\/scp>or messenger<scp>RNA<\/scp>point of departure estimates an apical endpoint point of departure in a rat developmental toxicity model"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-5566","authenticated-orcid":false,"given":"Kamin J.","family":"Johnson","sequence":"first","affiliation":[{"name":"Corteva Agriscience\u2122 Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Costa","sequence":"additional","affiliation":[{"name":"Corteva Agriscience\u2122, Mogi Mirim S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Marshall","sequence":"additional","affiliation":[{"name":"Labcorp Early Development Laboratories, Inc. 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