02773nas a2200349   4500000000100000008004100001260001500042653003100057653001500088653004400103653001900147100001500166700001700181700001500198700001900213700001700232700001300249700001500262700001400277700001100291700001300302700001600315700001500331700002100346700001600367700001800383245020900401856007200610300001100682520171600693022001402409       2025                            d  c2025-09-2710anew approach methodologies10aBiomarkers10adevelopmental and reproductive toxicity10ateratogenicity1 aM. Burbank1 aN. J. Hewitt1 aF. Gautier1 aA. Noel-Voisin1 aN. Golbamaki1 aR. Grall1 aM. Leonard1 aL. Carron1 aA. Riu1 aS. Emery1 aA. Detroyer1 aT. Bringel1 aL. Guillet-Revol1 aN. de Croze1 aG. Ouédraogo00aNew Approach Methodologies for evaluating Developmental And Reproductive Toxicity potential: review on state of the art, applicability for cosmetic related ingredients and coverage of developmental stages  uhttps://www.sciencedirect.com/science/article/pii/S3050620425000508  a1000553 aThe development of in vitro developmental and reproductive toxicity (DART) models is challenging. We made a brief review of in silico models and an in-depth review of 17 established in vitro New Approach Methodologies (NAMs) used to assess the DART potential of cosmetic-related ingredients. We investigated their coverage of the stages of male and female fertility and embryo-fetal development and related biomarkers to identify potential gaps. There are multiple in silico tools for early screening to flag DART potential, design subsequent testing, use in a weight of evidence approach or to fill data gaps. All stages of male and female fertility and embryo-fetal development are covered by at least one of the 17 NAMs evaluated, with most focusing on late organogenesis. Many NAMs measure specific receptors, enzymes and pathways involved in teratogenicity, highlighting the increased understanding of the pathways involved. Cellular endpoint assays are being refined by incorporating biomarker measurements. These can be combined in integrated and WoE approaches across different tiers in a testing strategy to cover different pathways to provide good confidence in the outcome of the testing. The most cited NAM in the literature was the zebrafish embryotoxicity test. This is not generally used for cosmetic-related ingredients, which are mainly evaluated using molecular and cellular assays related to steroidogenesis. The predictivity of several NAMs is increased when the measured or predicted plasma concentration is considered. In conclusion, this analysis indicates that currently available NAMs enable an analysis of the different stages of male and female fertility and embryo-fetal development.  a3050-6204