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

Belsito, D.; Bickers, D.; Bruze, Magnus LU ; Calow, P.; Dagli, M. L.; Fryer, A. D.; Greim, H.; Miyachi, Y.; Saurat, J. H. and Sipes, I. G. (2011) In Food and Chemical Toxicology 49(Suppl. 2). p.219-241
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... (More)
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. (C) 2011 Published by Elsevier Ltd. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Safety, Review, Fragrance, Macrocylic lactone, Macrocylic lactide
in
Food and Chemical Toxicology
volume
49
issue
Suppl. 2
pages
219 - 241
publisher
Elsevier
external identifiers
  • wos:000299404000023
  • scopus:84155167319
ISSN
0278-6915
DOI
10.1016/j.fct.2011.07.052
language
English
LU publication?
yes
id
0c1b8b41-88f1-46c6-bebc-c9f1b53f19fd (old id 2344980)
date added to LUP
2012-02-24 14:03:37
date last changed
2017-06-04 04:13:11
@article{0c1b8b41-88f1-46c6-bebc-c9f1b53f19fd,
  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. (C) 2011 Published by Elsevier Ltd.},
  author       = {Belsito, D. and Bickers, D. and Bruze, Magnus and Calow, P. and Dagli, M. L. and Fryer, A. D. and Greim, H. and Miyachi, Y. and Saurat, J. H. and Sipes, I. G.},
  issn         = {0278-6915},
  keyword      = {Safety,Review,Fragrance,Macrocylic lactone,Macrocylic lactide},
  language     = {eng},
  number       = {Suppl. 2},
  pages        = {219--241},
  publisher    = {Elsevier},
  series       = {Food and Chemical Toxicology},
  title        = {A toxicological and dermatological assessment of macrocyclic lactone and lactide derivatives when used as fragrance ingredients},
  url          = {http://dx.doi.org/10.1016/j.fct.2011.07.052},
  volume       = {49},
  year         = {2011},
}