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

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.