title: Hexyl cinnamal: consideration of skin-sensitizing properties and suitability as a positive control.
abstract: BACKGROUND
  Hexyl cinnamal (HCA) is a widely used fragrance chemical, the low skin-sensitizing potency of which has made it a common choice for the use as a positive control for predictive toxicology assays. However, HCA is commonly negative in current candidate in vitro alternatives test methods.
  
  
  OBJECTIVE
  To review the evidence that HCA is a classifiable skin sensitizer against the standards set by the Globally Harmonized Scheme (GHS), and determine whether it represents an appropriate choice for a positive control substance for predictive testing.
  
  
  METHODS
  Using the GHS criteria, mechanistic data, and in vitro, in vivo and human evidence relating to HCA and skin sensitization have been reviewed.
  
  
  RESULTS
  The chemistry of HCA is consistent with potential for skin sensitization and predictive in vivo test data support this conclusion. However, the human data are relatively sparse, consistent with HCA possessing a low capacity to induce skin sensitization under conditions of consumer exposures.
  
  
  CONCLUSIONS
  Using GHS criteria (and applying a precautionary approach) HCA would classify as a weaker skin sensitizer than predicted by the local lymph node assay (LLNA). However, given the human experience, it is necessary to consider whether HCA is the most appropriate choice for use as a positive regulatory control.
authors.affiliation: DABMEB Consultancy Ltd , Sharnbrook , UK .
authors.forename: David
authors.initials: D
authors.lastname: Basketter
authors.forename: Ian R
authors.initials: IR
authors.lastname: White
authors.forename: John P
authors.initials: JP
authors.lastname: McFadden
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D006168:Guinea Pigs; D006801:Humans; D009812:Odorants; D012867:Skin / Q000187:drug effects*
chemical_list: C080043:hexyl cinnamic aldehyde; D000171:Acrolein
keywords: Fragrance allergy; globally harmonized system; hexylcinnamal; in vivo sensitization; local lymph node assay; potency sub-categorization; skin sensitization