02322nas a2200313   4500000000100000008004100001260001500042653001300057653002300070653002100093653001300114653003300127653002300160653001200183100001900195700001600214700001700230700001800247700001700265700001700282700001900299700001500318700001500333245012100348856007200469300001100541520144200552022001401994       2026                            d  c2026-02-0210aGARDskin10aPoint of Departure10aRegression model10aSARA-ICE10aquantitative risk assessment10aSkin sensitization10atesting1 aAndreas Natsch1 aPeter Griem1 aAmaia Irizar1 aJames Bridges1 aMatthias Vey1 aIsabelle Lee1 aAnne Marie Api1 aPetra Kern1 aIan Kimber00aDerivation of a Point of Departure using NAMs for application in Quantitative Risk Assessment of fragrance materials  uhttps://www.sciencedirect.com/science/article/pii/S0273230026000255  a1060523 aSkin sensitization is a key endpoint for the safety assessment of topical consumer products. Ingredients with the potential to act as skin sensitizers differ markedly in their threshold for induction but can be used safely if their potency is characterized and exposure remains within an appropriate margin of safety. To this end, the fragrance industry co-developed Quantitative Risk Assessment (QRA) which starts with the No-Expected-Sensitization-Induction-Level (NESIL). Historically, QRA relies on a weight of evidence approach based on animal data, human confirmatory tests and read across. To allow an approach based solely on New Approach Methodologies (NAMs), the International Dialogue for the Evaluation of Allergens (IDEA) initiative, developed an extended Reference Chemical Potency List (RCPL) integrating human and animal data to derive potency values (PV). Here, we use PVs to evaluate the suitability of quantitative NAMs, including Defined Approaches (DAs), to derive a Point-of-Departure (NAM-PoD) for skin sensitization potency assessment. Evaluation of NAM-PoD derived by SARA-ICE DA, Regression DA and GARDskin dose-response assay (GSDR), indicates that the sensitization potency of fragrance chemicals can be reliably predicted using each approach. Through comparison of NAM-PoDs with in vivo human sensitization thresholds, NAM-specific adjustment factors were derived to convert NAM-PoDs into NAM-NESILs for QRA.  a0273-2300