PMID- 23534857
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20151103
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 26
IP  - 5
DP  - 2013 May 20
TI  - Skin sensitization of epoxyaldehydes: importance of conjugation.
PG  - 674-84
LID - 10.1021/tx300465h [doi]
AB  - Structure-activity relationship (SAR) models are important tools for predicting 
      the skin sensitization potential of new compounds without animal testing. In 
      compounds possessing a structural alert (aldehyde) and an activation alert 
      (double bond), it is important to consider bioactivation/autoxidation (e.g., 
      epoxidation). In the present study, we have explored a series of aldehydes with 
      regard to contact allergy. The chemical reactivity of these 6 aldehydes toward a 
      model hexapeptide was investigated, and their skin sensitization potencies were 
      evaluated using the local lymph node assay (LLNA). Overall, we observed a similar 
      trend for the in vitro reactivity and the in vivo sensitization potency for the 
      structural analogues in this study. The highly reactive conjugated aldehydes 
      (alpha,beta-unsaturated aldehydes and 2,3-epoxyaldehydes) are sensitizing moieties, 
      while nonconjugated aldehydes and nonterminal aliphatic epoxides show low 
      reactivity and low sensitization potency. Our data show the importance of not 
      only double bond conjugation to aldehyde but also epoxide-aldehyde conjugation. 
      The observations indicate that the formation of nonconjugated epoxides by 
      bioactivation or autoxidation is not sufficient to significantly increase the 
      sensitization potency of weakly sensitizing parent compounds.
FAU - Delaine, Tamara
AU  - Delaine T
AD  - Department of Chemistry and Molecular Biology, Dermatochemistry and Skin Allergy, 
      University of Gothenburg , SE-412 96 Gothenburg, Sweden. 
      tamara.delaine@chem.gu.se
FAU - Hagvall, Lina
AU  - Hagvall L
FAU - Rudback, Johanna
AU  - Rudback J
FAU - Luthman, Kristina
AU  - Luthman K
FAU - Karlberg, Ann-Therese
AU  - Karlberg AT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130423
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Aldehydes)
RN  - 0 (Allergens)
RN  - 0 (Epoxy Compounds)
SB  - IM
EIN - Chem Res Toxicol. 2014 Feb 17;27(2):309
MH  - Aldehydes/chemical synthesis/chemistry/*toxicity
MH  - Allergens/chemistry/*toxicity
MH  - Animals
MH  - Dermatitis, Allergic Contact/*etiology
MH  - Epoxy Compounds/chemical synthesis/chemistry/*toxicity
MH  - Female
MH  - Local Lymph Node Assay
MH  - Mice
MH  - Mice, Inbred CBA
EDAT- 2013/03/29 06:00
MHDA- 2014/12/23 06:00
CRDT- 2013/03/29 06:00
PHST- 2013/03/29 06:00 [entrez]
PHST- 2013/03/29 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
AID - 10.1021/tx300465h [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2013 May 20;26(5):674-84. doi: 10.1021/tx300465h. Epub 2013 Apr 
      23.