@article{7031,
  keywords = {GARDskin, Point of Departure, Regression model, SARA-ICE, quantitative risk assessment, Skin sensitization, testing},
  author = {Andreas Natsch and Peter Griem and Amaia Irizar and James Bridges and Matthias Vey and Isabelle Lee and Anne Marie Api and Petra Kern and Ian Kimber},
  title = {Derivation of a Point of Departure using NAMs for application in Quantitative Risk Assessment of fragrance materials},
  abstract = {Skin 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.},
  year = {2026},
  journal = {Regulatory Toxicology and Pharmacology},
  pages = {106052},
  month = {2026-02-02},
  issn = {0273-2300},
  url = {https://www.sciencedirect.com/science/article/pii/S0273230026000255},
  doi = {10.1016/j.yrtph.2026.106052},
}