title: Limonene hydroperoxide analogues differ in allergenic activity.
abstract: BACKGROUND
  The fragrance terpene R-limonene is a very weak sensitizer but forms allergenic oxidation products upon contact with air. Oxidized (ox.) limonene is a frequent cause of contact allergy in clinical testing.
  
  
  OBJECTIVE
  This study investigates the sensitizing potencies of ox. and non-ox. limonene and of structurally closely related limonene hydroperoxides. The clinical importance of the difference in sensitizing potency of two hydroperoxides in autoxidized limonene was studied.
  
  
  METHODS
  Ox. and non-ox. limonene were investigated in the murine local lymph node assay (LLNA). Limonene hydroperoxides were investigated using a modified LLNA involving non-pooled lymph nodes and statistical calculations; patch testing of patients with known contact allergy to ox. limonene was performed.
  
  
  RESULTS
  A marked increase in the sensitizing potency of ox. limonene compared with that of pure limonene was observed in the LLNA. One analogue, limonene-1-hydroperoxide, was a significantly more potent sensitizer than the other hydroperoxides and gave more positive test reactions in the allergic patients.
  
  
  CONCLUSIONS
  The results support that hydroperoxides have a specific reactivity indicating that oxygen-centred radicals are important in hapten-protein complex formation of hydroperoxides. The primary oxidation products of ox. limonene, the hydroperoxides, have an important impact on the sensitizing capacity of the oxidation mixture.
authors.affiliation: Dermatochemistry and Skin Allergy, Department of Chemistry, University of Gothenburg, SE-412 96 Gothenburg, Sweden. jacpth01@geh.regionh.dk
authors.forename: Johanna Bråred
authors.initials: JB
authors.lastname: Christensson
authors.forename: Staffan
authors.initials: S
authors.lastname: Johansson
authors.forename: Lina
authors.initials: L
authors.lastname: Hagvall
authors.forename: Charlotte
authors.initials: C
authors.lastname: Jonsson
authors.forename: Anna
authors.initials: A
authors.lastname: Börje
authors.forename: Ann-Therese
authors.initials: AT
authors.lastname: Karlberg
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D053138:Cyclohexenes / Q000009:adverse effects*; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects*; D000077222:Limonene; D023441:Local Lymph Node Assay; D008297:Male; D051379:Mice; D008875:Middle Aged; D010084:Oxidation-Reduction; D010328:Patch Tests / Q000379:methods; D010476:Perfume / Q000009:adverse effects*; D012997:Solvents / Q000009:adverse effects*; D013729:Terpenes / Q000009:adverse effects*
chemical_list: D053138:Cyclohexenes; D010476:Perfume; D012997:Solvents; D013729:Terpenes; D000077222:Limonene; D006861:Hydrogen Peroxide