2. Academic Validation
  3. Update to RIFM fragrance ingredient safety assessment, γ-hexalactone, CAS Registry Number 695-06-7

Update to RIFM fragrance ingredient safety assessment, γ-hexalactone, CAS Registry Number 695-06-7

  • Food Chem Toxicol. 2026 Apr:210 Suppl 1:115886. doi: 10.1016/j.fct.2025.115886.
A M Api 1,  A Bartlett 1,  D Belsito 2,  D Botelho 1,  M Bruze 3,  A Bryant-Friedrich 4,  G A Burton Jr 5,  M A Cancellieri 1,  H Chon 1,  M Cronin 6,  S Crotty 1,  M L Dagli 7,  W Dekant 8,  C Deodhar 1,  K Farrell 1,  A D Fryer 9,  L Jones 1,  K Joshi 1,  A Lapczynski 1,  D L Laskin 10,  M Lavelle 1,  I Lee 1,  H Moustakas 1,  J Muldoon 1,  T M Penning 11,  A H Piersma 12,  G Ritacco 1,  N Sadekar 1,  I Schember 1,  T W Schultz 11,  F Siddiqi 1,  I G Sipes 13,  G Sullivan 14,  Y Thakkar 1
Affiliations

Affiliations

  • 1 Research Institute for Fragrance Materials, Inc., 1200 MacArthur Boulevard, Suite 306, Mahwah, NJ, 07430, USA.
  • 2 Expert Panel for Fragrance Safety, Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave., New York, NY, 10032, USA.
  • 3 Expert Panel for Fragrance Safety, Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo, SE-20502, Sweden.
  • 4 Expert Panel for Fragrance Safety, Pharmaceutical Sciences, Wayne State University, 42 W. Warren Ave., Detroit, MI, 48202, USA.
  • 5 Expert Panel for Fragrance Safety, School of Natural Resources & Environment, University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI, 58109, USA.
  • 6 Expert Panel for Fragrance Safety, Liverpool John Moores University, School of Pharmacy and Biomolecular Sciences, Liverpool, United Kingdom.
  • 7 Expert Panel for Fragrance Safety, University of Sao Paulo, School of Veterinary Medicine and Animal Science, Department of Pathology, Av. Prof. dr. Orlando Marques de Paiva, 87, Sao Paulo, CEP 05508-900, Brazil.
  • 8 Expert Panel for Fragrance Safety, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078, Würzburg, Germany.
  • 9 Expert Panel for Fragrance Safety, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA.
  • 10 Expert Panel for Fragrance Safety, Rutgers University Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
  • 11 Expert Panel for Fragrance Safety, University of Pennsylvania, Perelman School of Medicine, Center of Excellence in Environmental Toxicology, 1316 Biomedical Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, PA, 19104-3083, USA.
  • 12 Expert Panel for Fragrance Safety, Utrecht University, Institute for Risk Assessment Sciences (IRAS), Netherlands.
  • 13 Expert Panel for Fragrance Safety, Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ, 85724-5050, USA.
  • 14 Research Institute for Fragrance Materials, Inc., 1200 MacArthur Boulevard, Suite 306, Mahwah, NJ, 07430, USA. Electronic address: [email protected].
PMID: 41354121 DOI: 10.1016/j.fct.2025.115886
Abstract

γ-Hexalactone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog γ-valerolactone (CAS # 108-29-2) show that γ-hexalactone is not expected to be genotoxic. Data on γ-hexalactone provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity and developmental toxicity endpoints. Data on read-across analog γ-dodecalactone (CAS # 2305-05-7) provide a calculated MOE >100 for the fertility endpoint. Data from read-across analog 4-hydroxybutanoic acid lactone (CAS # 96-48-0) show that there are no safety concerns for γ-hexalactone for skin sensitization under the current declared levels of use. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; γ-hexalactone is not expected to be photoirritating/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material, and the exposure to γ-hexalactone is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; γ-hexalactone was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use (VoU) in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

Figures
Products