PMID- 15128320
OWN - NLM
STAT- MEDLINE
DCOM- 20041007
LR  - 20061115
IS  - 0105-1873 (Print)
IS  - 0105-1873 (Linking)
VI  - 50
IP  - 2
DP  - 2004 Feb
TI  - Further evaluation of quantitative structure--activity relationship models for 
      the prediction of the skin sensitization potency of selected fragrance allergens.
PG  - 91-7
AB  - Fragrance substances represent a very diverse group of chemicals; a proportion of 
      them are associated with the ability to cause allergic reactions in the skin. 
      Efforts to find substitute materials are hindered by the need to undertake animal 
      testing for determining both skin sensitization hazard and potency. One strategy 
      to avoid such testing is through an understanding of the relationships between 
      chemical structure and skin sensitization, so-called structure-activity 
      relationships. In recent work, we evaluated 2 groups of fragrance chemicals -- 
      saturated aldehydes and alpha,beta-unsaturated aldehydes. Simple quantitative 
      structure-activity relationship (QSAR) models relating the EC3 values [derived 
      from the local lymph node assay (LLNA)] to physicochemical properties were 
      developed for both sets of aldehydes. In the current study, we evaluated an 
      additional group of carbonyl-containing compounds to test the predictive power of 
      the developed QSARs and to extend their scope. The QSAR models were used to 
      predict EC3 values of 10 newly selected compounds. Local lymph node assay data 
      generated for these compounds demonstrated that the original QSARs were fairly 
      accurate, but still required improvement. Development of these QSAR models has 
      provided us with a better understanding of the potential mechanisms of action for 
      aldehydes, and hence how to avoid or limit allergy. Knowledge generated from this 
      work is being incorporated into new/improved rules for sensitization in the 
      expert toxicity prediction system, deductive estimation of risk from existing 
      knowledge (DEREK).
FAU - Patlewicz, Grace Y
AU  - Patlewicz GY
AD  - Safety and Environmental Assurance Centre, Unilever Colworth, Colworth House, 
      Sharnbrook, Bedford, UK. grace.patlewicz@unilever.com
FAU - Basketter, David A
AU  - Basketter DA
FAU - Pease, Camilla K Smith
AU  - Pease CK
FAU - Wilson, Karen
AU  - Wilson K
FAU - Wright, Zoe M
AU  - Wright ZM
FAU - Roberts, David W
AU  - Roberts DW
FAU - Bernard, Guillaume
AU  - Bernard G
FAU - Arnau, Elena Gimenez
AU  - Arnau EG
FAU - Lepoittevin, Jean-Pierre
AU  - Lepoittevin JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Contact Dermatitis
JT  - Contact dermatitis
JID - 7604950
RN  - 0 (Aldehydes)
RN  - 0 (Allergens)
RN  - 0 (Perfume)
SB  - IM
MH  - Aldehydes/*chemistry/pharmacology
MH  - Allergens/*chemistry/pharmacology
MH  - Lymph Nodes/drug effects
MH  - *Models, Statistical
MH  - Perfume/*chemistry/pharmacology
MH  - Predictive Value of Tests
MH  - Structure-Activity Relationship
EDAT- 2004/05/07 05:00
MHDA- 2004/10/08 09:00
CRDT- 2004/05/07 05:00
PHST- 2004/05/07 05:00 [pubmed]
PHST- 2004/10/08 09:00 [medline]
PHST- 2004/05/07 05:00 [entrez]
AID - COD322 [pii]
AID - 10.1111/j.0105-1873.2004.00322.x [doi]
PST - ppublish
SO  - Contact Dermatitis. 2004 Feb;50(2):91-7. doi: 10.1111/j.0105-1873.2004.00322.x.