PMID- 20163165
OWN - NLM
STAT- MEDLINE
DCOM- 20100629
LR  - 20181201
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 23
IP  - 3
DP  - 2010 Mar 15
TI  - Structural influence on radical formation and sensitizing capacity of alkylic 
      limonene hydroperoxide analogues in allergic contact dermatitis.
PG  - 677-88
LID - 10.1021/tx900433n [doi]
AB  - Hydroperoxides are known to be strong contact allergens and a common cause of 
      contact allergy. They are easily formed by the autoxidation of, for example, 
      fragrance terpenes, compounds that are common in perfumes, cosmetics, and 
      household products. A requirement of the immunological mechanisms of contact 
      allergy is the formation of an immunogenic hapten-protein complex. For 
      hydroperoxides, a radical mechanism is postulated for this formation. In our 
      previous investigations of allylic limonene hydroperoxides, we found that the 
      formation of carbon- and oxygen-centered radicals, as well as the sensitizing 
      capacity, is influenced by the structure of the hydroperoxides. The aim of the 
      present work was to further investigate the connection between structure, radical 
      formation, and sensitizing capacity by studying alkylic analogues of the 
      previously investigated allylic limonene hydroperoxides. The radical formation 
      was studied in radical-trapping experiments employing 
      5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride as an initiator and 
      1,1,3,3-tetramethylisoindolin-2-yloxyl as a radical trapper. We found that the 
      investigated hydroperoxides initially form carbon- and oxygen-centered radicals 
      that subsequently form alcohols and ketones. Trapped carbon-centered radicals and 
      nonradical products were isolated and identified. Small changes in structure, 
      like the omission of the endocyclic double bond or the addition of a methyl 
      group, resulted in large differences in radical formation. The results indicate 
      that alkoxyl radicals seem to be more important than carbon-centered radicals in 
      the immunogenic complex formation. The sensitizing capacities were studied in the 
      murine local lymph node assay (LLNA), and all hydroperoxides tested were found to 
      be potent sensitizers. For two of the hydroperoxides investigated, the recently 
      suggested thiol-ene reaction is a possible mechanism for the formation of 
      immunogenic complexes. For the third investigated, fully saturated, 
      hydroperoxide, the thiol-ene mechanism is not possible for immunogenic complex 
      formation. This strongly indicates that several radical reaction pathways for 
      immunogenic complex formation of limonene hydroperoxides are active in parallel.
FAU - Johansson, Staffan G H
AU  - Johansson SG
AD  - Dermatochemistry and Skin Allergy and Medicinal Chemistry, Department of 
      Chemistry, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
FAU - Emilsson, Katarina
AU  - Emilsson K
FAU - Grotli, Morten
AU  - Grotli M
FAU - Borje, Anna
AU  - Borje A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Allergens)
RN  - 0 (Cyclohexenes)
RN  - 0 (Haptens)
RN  - 0 (Terpenes)
RN  - 9MC3I34447 (Limonene)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Allergens/*chemistry/*immunology
MH  - Animals
MH  - Cyclohexenes/*chemistry/*immunology
MH  - Dermatitis, Allergic Contact/drug therapy
MH  - Haptens/chemistry/immunology
MH  - Humans
MH  - Hydrogen Peroxide/*chemistry/*immunology
MH  - Limonene
MH  - Mice
MH  - Terpenes/*chemistry/*immunology
EDAT- 2010/02/19 06:00
MHDA- 2010/06/30 06:00
CRDT- 2010/02/19 06:00
PHST- 2010/02/19 06:00 [entrez]
PHST- 2010/02/19 06:00 [pubmed]
PHST- 2010/06/30 06:00 [medline]
AID - 10.1021/tx900433n [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2010 Mar 15;23(3):677-88. doi: 10.1021/tx900433n.