RIFM fragrance ingredient safety assessment, 3,4,4a,5,8,8a(Or 3,4,4a,7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran, CAS Registry Number 72429-08-4

A M Api; D Belsito; S Biserta; D Botelho; M Bruze; G A Burton Jr; J Buschmann; M A Cancellieri; M L Dagli; M Date; W Dekant; C Deodhar; A D Fryer; S Gadhia; L Jones; K Joshi; M Kumar; A Lapczynski; M Lavelle; I Lee; D C Liebler; H Moustakas; M Na; T M Penning; G Ritacco; J Romine; N Sadekar; T W Schultz; D Selechnik; F Siddiqi; I G Sipes; G Sullivan; Y Thakkar; Y Tokura

doi:10.1016/j.fct.2020.111885

RIFM fragrance ingredient safety assessment, 3,4,4a,5,8,8a(Or 3,4,4a,7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran, CAS Registry Number 72429-08-4

Food Chem Toxicol. 2021 Mar:149 Suppl 1:111885. doi: 10.1016/j.fct.2020.111885. Epub 2020 Nov 26.

Authors

A M Api¹, D Belsito², S Biserta¹, D Botelho¹, M Bruze³, G A Burton Jr⁴, J Buschmann⁵, M A Cancellieri¹, M L Dagli⁶, M Date¹, W Dekant⁷, C Deodhar¹, A D Fryer⁸, S Gadhia¹, L Jones¹, K Joshi¹, M Kumar¹, A Lapczynski¹, M Lavelle¹, I Lee¹, D C Liebler⁹, H Moustakas¹, M Na¹, T M Penning¹⁰, G Ritacco¹, J Romine¹, N Sadekar¹, T W Schultz¹¹, D Selechnik¹, F Siddiqi¹, I G Sipes¹², G Sullivan¹³, Y Thakkar¹, Y Tokura¹⁴

Affiliations

¹ Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, 07677, USA.
² Member Expert Panel, Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave., New York, NY, 10032, USA.
³ Member Expert Panel, Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo, SE, 20502, Sweden.
⁴ Member Expert Panel, School of Natural Resources & Environment, University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI, 58109, USA.
⁵ Member Expert Panel, Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625, Hannover, Germany.
⁶ Member Expert Panel, 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.
⁷ Member Expert Panel, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078, Würzburg, Germany.
⁸ Member Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239, USA.
⁹ Member Expert Panel, Vanderbilt University School of Medicine, Department of Biochemistry, Center in Molecular Toxicology, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN, 37232-0146, USA.
¹⁰ Member of Expert Panel, 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.
¹¹ Member Expert Panel, The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN, 37996- 4500, USA.
¹² Member Expert Panel, Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ, 85724-5050, USA.
¹³ Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ, 07677, USA. Electronic address: gsullivan@rifm.org.
¹⁴ Member Expert Panel, The Journal of Dermatological Science (JDS), Editor-in-Chief, Professor and Chairman, Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.

PMID: 33249051
DOI: 10.1016/j.fct.2020.111885

Abstract

The existing information supports the use of this material as described in this safety assessment. 3,4,4a,5,8,8a (Or 3,4,4a,7,8,8a)-Hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 3,4,4a, 5,8,8a (Or 3,4,4a, 7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to 3,4,4a, 5,8,8a (Or 3,4,4a, 7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 μg/cm²); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 3,4,4a, 5,8,8a (Or 3,4,4a,7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 3,4,4a, 5,8,8a (Or 3,4,4a, 7,8,8a)-hexahydro-3,3,6,7-tetramethyl-1H-2-benzopyran 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 in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

Keywords: Environmental Safety; Genotoxicity; Local Respiratory Toxicity; Phototoxicity/Photoallergenicity; Repeated Dose, Developmental, and Reproductive Toxicity; Skin Sensitization.

Publication types

Review

MeSH terms

Animals
Dose-Response Relationship, Drug
Humans
Odorants*
Quantitative Structure-Activity Relationship
Reproduction / drug effects
Risk Assessment
Toxicity Tests