PMID- 17555332
OWN - NLM
STAT- MEDLINE
DCOM- 20071009
LR  - 20220311
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 20
IP  - 7
DP  - 2007 Jul
TI  - Mechanistic applicability domain classification of a local lymph node assay 
      dataset for skin sensitization.
PG  - 1019-30
AB  - The goal of eliminating animal testing in the predictive identification of 
      chemicals with the intrinsic ability to cause skin sensitization is an important 
      target, the attainment of which has recently been brought into even sharper 
      relief by the EU Cosmetics Directive and the requirements of the REACH 
      legislation. Development of alternative methods requires that the chemicals used 
      to evaluate and validate novel approaches comprise not only confirmed skin 
      sensitizers and non-sensitizers but also substances that span the full chemical 
      mechanistic spectrum associated with skin sensitization. To this end, a recently 
      published database of more than 200 chemicals tested in the mouse local lymph 
      node assay (LLNA) has been examined in relation to various chemical reaction 
      mechanistic domains known to be associated with sensitization. It is demonstrated 
      here that the dataset does cover the main reaction mechanistic domains. In 
      addition, it is shown that assignment to a reaction mechanistic domain is a 
      critical first step in a strategic approach to understanding, ultimately on a 
      quantitative basis, how chemical properties influence the potency of skin 
      sensitizing chemicals. This understanding is necessary if reliable non-animal 
      approaches, including (quantitative) structure-activity relationships (Q)SARs, 
      read-across, and experimental chemistry based models, are to be developed.
FAU - Roberts, David W
AU  - Roberts DW
AD  - School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, 
      UK.
FAU - Patlewicz, Grace
AU  - Patlewicz G
FAU - Kern, Petra S
AU  - Kern PS
FAU - Gerberick, Frank
AU  - Gerberick F
FAU - Kimber, Ian
AU  - Kimber I
FAU - Dearman, Rebecca J
AU  - Dearman RJ
FAU - Ryan, Cindy A
AU  - Ryan CA
FAU - Basketter, David A
AU  - Basketter DA
FAU - Aptula, Aynur O
AU  - Aptula AO
LA  - eng
PT  - Journal Article
DEP - 20070608
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Algorithms
MH  - Animal Testing Alternatives
MH  - Animals
MH  - Databases, Factual/classification/*statistics & numerical data
MH  - Drug Eruptions/diagnosis/etiology
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Humans
MH  - *Local Lymph Node Assay
MH  - Mice
MH  - Molecular Structure
MH  - Pharmaceutical Preparations/*administration & dosage/chemistry
MH  - Quantitative Structure-Activity Relationship
MH  - Reproducibility of Results
MH  - Skin/*drug effects/pathology
MH  - Toxicity Tests/methods/trends
EDAT- 2007/06/09 09:00
MHDA- 2007/10/10 09:00
CRDT- 2007/06/09 09:00
PHST- 2007/06/09 09:00 [pubmed]
PHST- 2007/10/10 09:00 [medline]
PHST- 2007/06/09 09:00 [entrez]
AID - 10.1021/tx700024w [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2007 Jul;20(7):1019-30. doi: 10.1021/tx700024w. Epub 2007 Jun 
      8.