Epoxyalcohols: bioactivation and conjugation required for skin sensitization.
Chem Res Toxicol
; 27(10): 1860-70, 2014 Oct 20.
Article
in En
| MEDLINE
| ID: mdl-25195701
ABSTRACT
Allylic alcohols, such as geraniol 1, are easily oxidized by varying mechanisms, including the formation of both 2,3-epoxides and/or aldehydes. These epoxides, aldehydes, and epoxy-aldehydes can be interconverted to each other, and the reactivity of them all must be considered when considering the sensitization potential of the parent allylic alcohol. An in-depth study of the possible metabolites and autoxidation products of allylic alcohols is described, covering the formation, interconversion, reactivity, and sensitizing potential thereof, using a combination of in vivo, in vitro, in chemico, and in silico methods. This multimodal study, using the integration of diverse techniques to investigate the sensitization potential of a molecule, allows the identification of potential candidate(s) for the true culprit(s) in allergic responses to allylic alcohols. Overall, the sensitization potential of the investigated epoxyalcohols and unsaturated alcohols was found to derive from metabolic oxidation to the more potent aldehyde where possible. Where this is less likely, the compound remains weakly or nonsensitizing. Metabolic activation of a double bond to form a nonconjugated, nonterminal epoxide moiety is not enough to turn a nonsensitizing alcohol into a sensitizer, as such epoxides have low reactivity and low sensitizing potency. In addition, even an allylic 2,3-epoxide moiety is not necessarily a potent sensitizer, as shown for 2, where formation of the epoxide weakens the sensitization potential.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Terpenes
/
Propanols
/
Epoxy Compounds
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Chem Res Toxicol
Journal subject:
TOXICOLOGIA
Year:
2014
Document type:
Article
Affiliation country:
Sweden