A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, M A Guttenberg, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, F Siddiqi, G Sullivan, Y Thakkar
Two peer-reviewed Criteria Documents, one for discrete fragrance ingredients (2015) and another for Natural Complex Substances (NCS) (2022), form the scientific basis for the safety evaluation of an inventory of over 3,000 fragrance materials. Both documents outline a stepwise, endpoint-specific approach to safety assessment. While the overall framework is consistent across toxicological endpoints, variations exist due to differences in toxicological assessment via thresholds of toxicological concern (TTCs), and the application of new approach methodologies (NAMs) where validated methods are available. Since the publication of the original Criteria Documents, the Research Institute for Fragrance Materials (RIFM) has released several manuscripts detailing updates and scientific advances across individual toxicological endpoints. These ongoing improvements have been incorporated into RIFM's internal safety assessment processes, even if they have not yet been reflected in the published Criteria Documents. This manuscript will provide a comprehensive overview of the current safety evaluation process, acknowledging the dynamic nature of toxicological science, and the likelihood of continued refinement over time.