PMID- 9305580
OWN - NLM
STAT- MEDLINE
DCOM- 19980113
LR  - 20061115
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 10
IP  - 9
DP  - 1997 Sep
TI  - Skin sensitization to linalyl hydroperoxide: support for radical intermediates.
PG  - 987-93
AB  - In order to better understand the skin sensitization mechanism of allylic 
      hydroperoxides, linalyl hydroperoxide (1) and several of its potential 
      rearrangement products-epoxylinalool (2), epoxynerol (3), epoxygeraniol (4), and 
      furan (5) and pyran (6) derivatives-were synthesized. The sensitizing properties 
      of these molecules have been screened on mice using the local lymph node assay 
      (LLNA) and further evaluated on guinea pigs using the Freund's complete adjuvant 
      test (FCAT). Linalyl hydroperoxide (1) and linalyl epoxide (2) were found to be 
      sensitizers, while the other compounds were classified as mild sensitizers or 
      nonsensitizers. In the guinea pigs, no cross-reactions were observed between skin 
      sensitizers 1 and 2. Radical-trapping experiments were carried out on linalyl 
      hydroperoxide (1) using TTBP as trapping agent and Fe(3+)-TPP as radical inducer. 
      The major reaction taking place is the formation of a furan ring by 
      intramolecular reaction of the oxygen-centered radical with the isoprenyl double 
      bond with the formation of a tertiary radical. Reaction of this intermediate with 
      radicals derived from TTBP gave compounds 10a,b in 25% yield. The second 
      important reaction, accounting for 14%, is taking place on the allylic double 
      bond with the formation of a less stable primary radical which is not trapped by 
      a TTBP-derived radical but by a hydroxy radical to give a mixture of epoxides 3 
      and 4. These results are in favor of the formation of a carbon-centered reactive 
      radical as intermediate in the skin sensitization to linalyl hydroperoxide.
FAU - Bezard, M
AU  - Bezard M
AD  - Laboratoire de Dermatochimie associe au CNRS, Universite Louis Pasteur, Clinique 
      Dermatologique, CHU, Strasbourg, France.
FAU - Karlberg, A T
AU  - Karlberg AT
FAU - Montelius, J
AU  - Montelius J
FAU - Lepoittevin, J P
AU  - Lepoittevin JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Free Radicals)
RN  - 0 (Monoterpenes)
RN  - 0 (Peroxides)
RN  - 0 (Terpenes)
RN  - 0 (linalyl hydroperoxide)
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
MH  - Animals
MH  - Cross Reactions
MH  - Dermatitis, Irritant/*metabolism
MH  - Female
MH  - Free Radical Scavengers/pharmacology
MH  - Free Radicals
MH  - Freund's Adjuvant
MH  - Guinea Pigs
MH  - Lymph Nodes/chemistry
MH  - Magnetic Resonance Spectroscopy
MH  - Mice
MH  - Mice, Inbred CBA
MH  - *Monoterpenes
MH  - Peroxides/chemistry/*toxicity
MH  - Terpenes/chemistry/*toxicity
EDAT- 1997/09/26 00:00
MHDA- 1997/09/26 00:01
CRDT- 1997/09/26 00:00
PHST- 1997/09/26 00:00 [pubmed]
PHST- 1997/09/26 00:01 [medline]
PHST- 1997/09/26 00:00 [entrez]
AID - tx970014r [pii]
AID - 10.1021/tx970014r [doi]
PST - ppublish
SO  - Chem Res Toxicol. 1997 Sep;10(9):987-93. doi: 10.1021/tx970014r.