02547nas a2200325   4500000000100000000000100001008004100002260001100043653001600054653003600070653002300106653002500129653003800154100002000192700002100212700001900233700002100252700001500273700002000288700002700308700001900335700001900354700001700373245016400390856004700554300001000601490000700611520158900618022001402207       2022                            d  c2022/110aOECD TG 41410aadverse outcome pathways (AOPs)10aanimal replacement10aendocrine disruptors10aNew Approach Methodologies (NAMs)1 aMichaela Luconi1 aMiguel A. Sogorb1 aUdo R. Markert1 aEmilio Benfenati1 aTobias May1 aSusanne Wolbank1 aAlessandra Roncaglioni1 aAstrid Schmidt1 aMarco Straccia1 aSabrina Tait00aHuman-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto–Placental Organ-on-Chip Platform  uhttps://www.mdpi.com/1660-4601/19/23/15828  a158280 v193 aDevelopmental toxicity testing urgently requires the implementation of human-relevant new approach methodologies (NAMs) that better recapitulate the peculiar nature of human physiology during pregnancy, especially the placenta and the maternal/fetal interface, which represent a key stage for human lifelong health. Fit-for-purpose NAMs for the placental–fetal interface are desirable to improve the biological knowledge of environmental exposure at the molecular level and to reduce the high cost, time and ethical impact of animal studies. This article reviews the state of the art on the available in vitro (placental, fetal and amniotic cell-based systems) and in silico NAMs of human relevance for developmental toxicity testing purposes; in addition, we considered available Adverse Outcome Pathways related to developmental toxicity. The OECD TG 414 for the identification and assessment of deleterious effects of prenatal exposure to chemicals on developing organisms will be discussed to delineate the regulatory context and to better debate what is missing and needed in the context of the Developmental Origins of Health and Disease hypothesis to significantly improve this sector. Starting from this analysis, the development of a novel human feto–placental organ-on-chip platform will be introduced as an innovative future alternative tool for developmental toxicity testing, considering possible implementation and validation strategies to overcome the limitation of the current animal studies and NAMs available in regulatory toxicology and in the biomedical field.  a1660-4601