A toxicological and dermatological assessment of macrocyclic ketones when used as fragrance ingredients* The RIFM Expert Panel

Research output: Contribution to journalReview article


The macrocyclic ketone (MK) group of fragrance ingredients was evaluated for safety following a complete literature search. For high end users, calculated maximum dermal exposures vary from 0.13% to 1.10%; systemic exposures vary from 0.0005 to 0.0441 mg/kg/day. The MKs had low acute toxicity and no significant repeat dose toxicity. Liver weight and blood biochemistry effects were reversible after 2 weeks. No genotoxicity in bacteria and mammalian cell lines was observed. Reproductive toxicity was not observed for 3-methylcyclopentadecenone in an OECD compliant study. In humans, MKs are generally not irritating after one application. Animal studies showed irritation for some materials at concentrations higher than current consumer exposure. At rates consistent with current human exposure, phototoxicity and photosensitization were not observed. In animals, some MKs are sensitizers only at concentrations of 20%, 30%, or 100%, which are higher than current consumer exposure. No evidence of sensitization was observed in human tests. In patients with fragrance allergy, reactions were seen with cyclopentadecanone (3/178). Based on these findings, the Panel is of the opinion that there are no safety concerns for the MKs at reported levels of use and exposure as fragrance ingredients. (C) 2011 Published by Elsevier Ltd.


  • D. Belsito
  • D. Bickers
  • Magnus Bruze
  • P. Calow
  • M. L. Dagli
  • A. D. Fryer
  • H. Greim
  • Y. Miyachi
  • J. H. Saurat
  • I. G. Sipes
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology


  • Safety, Review, Fragrance, Macrocyclic ketone
Original languageEnglish
Pages (from-to)S126-S141
JournalFood and Chemical Toxicology
Issue numberSuppl. 2
Publication statusPublished - 2011
Publication categoryResearch