A toxicological and dermatological assessment of macrocyclic lactone and lactide derivatives when used as fragrance ingredients

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 article

22 Scopus citations

Abstract

The Macrocyclic Lactone and Lactide derivative (ML) group of fragrance ingredients was critically evaluated for safety following a complete literature search. For high end users, calculated maximum dermal exposures vary from 0.47% to 11.15%; systemic exposures vary from 0.0008 to 0.25. mg/kg/day. The MLs had low acute toxicity and no significant toxicity in repeat dose oral ordermal toxicity studies. Effects on blood biochemistry were reversible after 2. weeks of no treatment. No mutagenic or genotoxic activity in bacteria and mammalian cell line assays was observed. Reproductive and developmental toxicity was not observed. Human dermatological studies show MLs are generally not irritating after one application. Minor irritation was observed in a few individuals following multiple applications. At rates consistent with reported levels for current human exposure, no phototoxicity or photosensitization was observed. In animal studies, the MLs are not sensitizers at lower exposures from consumer products. Eleven ML materials were evaluated for human sensitization. Of these, only ethylene brassylate showed evidence of sensitization in 2/27 studies (sensitization frequency 4/2059 total). Based on these findings, the Panel is of the opinion that there are no safety concerns for the MLs at reported levels of use and exposure as fragrance ingredients.

Original languageEnglish (US)
Pages (from-to)S219-S241
JournalFood and Chemical Toxicology
Volume49
Issue numberSUPPL. 2
DOIs
StatePublished - Dec 1 2011

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Keywords

  • Fragrance
  • Macrocylic lactide
  • Macrocylic lactone
  • Review
  • Safety

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M. L., Fryer, A. D., Greim, H., Miyachi, Y., Saurat, J. H., & Sipes, I. G. (2011). A toxicological and dermatological assessment of macrocyclic lactone and lactide derivatives when used as fragrance ingredients. Food and Chemical Toxicology, 49(SUPPL. 2), S219-S241. https://doi.org/10.1016/j.fct.2011.07.052