2. Academic Validation
  3. RIFM fragrance ingredient safety assessment, 4-methylpentanoic acid, CAS Registry Number 646-07-1

RIFM fragrance ingredient safety assessment, 4-methylpentanoic acid, CAS Registry Number 646-07-1

  • Food Chem Toxicol. 2020 Oct 15:144 Suppl 1:111456. doi: 10.1016/j.fct.2020.111456.
A M Api 1,  D Belsito 2,  S Biserta 1,  D Botelho 1,  M Bruze 3,  G A Burton Jr 4,  J Buschmann 5,  M A Cancellieri 1,  M L Dagli 6,  M Date 1,  W Dekant 7,  C Deodhar 1,  A D Fryer 8,  S Gadhia 1,  L Jones 1,  K Joshi 1,  A Lapczynski 1,  M Lavelle 1,  D C Liebler 9,  M Na 1,  D O'Brien 1,  A Patel 1,  T M Penning 10,  G Ritacco 1,  F Rodriguez-Ropero 1,  J Romine 1,  N Sadekar 1,  D Salvito 1,  T W Schultz 11,  F Siddiqi 1,  I G Sipes 12,  G Sullivan 13,  Y Thakkar 1,  Y Tokura 14,  S Tsang 1
Affiliations

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: [email protected].
  • 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: 32640362 DOI: 10.1016/j.fct.2020.111456
Abstract

The existing information supports the use of this material as described in this safety assessment. 4-Methylpentanoic acid was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog 2-ethylbutyric acid (CAS # 88-09-5) show that 4-methylpentanoic acid is not expected to be genotoxic and provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. 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; 4-methylpentanoic acid is not expected to be phototoxic/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 4-methylpentanoic acid is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 4-methylpentanoic acid 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.

Figures
Products