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

D. Belsito, D. Bickers, M. Bruze, P. Calow, M. L. Dagli, A. D. Fryer, H. Greim, Y. Miyachi, J. H. Saurat, I. G. Sipes

    Research output: Contribution to journalReview articlepeer-review

    18 Scopus citations


    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.

    Original languageEnglish (US)
    Pages (from-to)S126-S141
    JournalFood and Chemical Toxicology
    Issue numberSUPPL. 2
    StatePublished - Dec 2011

    Bibliographical note

    Funding Information:
    This research was supported by the Research Interest for Fragrance Materials , an independent research institute that is funded by the manufacturers of fragrances and consumer products containing fragrances. The authors are all members of the Expert Panel of the Research Institute for Fragrance Materials, an independent group of experts who evaluate the safety of fragrance materials.


    • Fragrance
    • Macrocyclic ketone
    • Review
    • Safety

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