PMID- 16045286
OWN - NLM
STAT- MEDLINE
DCOM- 20060524
LR  - 20220311
IS  - 1549-9596 (Print)
IS  - 1549-9596 (Linking)
VI  - 45
IP  - 4
DP  - 2005 Jul-Aug
TI  - Quantum mechanical structure-activity relationship analyses for skin 
      sensitization.
PG  - 924-9
AB  - Allergic contact dermatitis (ACD) results in inflammation of the skin due to 
      sensitization of the immunologic system to a particular substance. The 
      sensitization process is limited by the compound's ability to both permeate and 
      react with proteins in the integumentary system. Currently, only in vivo animal 
      tests such as the local lymph node assay (LLNA) are recognized by regulatory 
      authorities for risk assessment of ACD. A quantitative structure-activity 
      relationship has been developed to predict relative potency, which allows for the 
      prediction of relative sensitization potentials. The experimental values used in 
      this study include EC3 values (the concentration at which the stimulation index 
      equals 3) from LLNA tests. The predictions in this model enable categorization of 
      the compounds into three groups on the basis of risk of sensitization and enable 
      screening of candidate molecules using rapid SAM1 semiempirical calculations 
      prior to animal testing. The model may also be used to reduce the number of 
      animals subjected to testing by providing estimated concentrations required for 
      useful data of risk assessment. The effect of averaging available literature 
      values on predictive ability is also investigated. The model includes halogenated 
      compounds, aromatic compounds, alcohols, aldehydes, and ketones. The 
      computational investigation resulted in a two-descriptor model that is consistent 
      with the assumed mechanism for sensitization.
FAU - Miller, Matthew D
AU  - Miller MD
AD  - Department of Chemistry, University of Missouri, Kansas City, Kansas City, 
      Missouri 64110, USA.
FAU - Yourtee, David M
AU  - Yourtee DM
FAU - Glaros, Alan G
AU  - Glaros AG
FAU - Chappelow, Cecil C
AU  - Chappelow CC
FAU - Eick, J David
AU  - Eick JD
FAU - Holder, Andrew J
AU  - Holder AJ
LA  - eng
GR  - DE07294/DE/NIDCR NIH HHS/United States
GR  - DE09696/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Chem Inf Model
JT  - Journal of chemical information and modeling
JID - 101230060
SB  - IM
MH  - *Hypersensitivity/immunology
MH  - *Models, Immunological
MH  - *Quantitative Structure-Activity Relationship
MH  - *Quantum Theory
MH  - Risk Assessment
MH  - *Skin/immunology
EDAT- 2005/07/28 09:00
MHDA- 2006/05/25 09:00
CRDT- 2005/07/28 09:00
PHST- 2005/07/28 09:00 [pubmed]
PHST- 2006/05/25 09:00 [medline]
PHST- 2005/07/28 09:00 [entrez]
AID - 10.1021/ci050018z [doi]
PST - ppublish
SO  - J Chem Inf Model. 2005 Jul-Aug;45(4):924-9. doi: 10.1021/ci050018z.