PMID- 12074383
OWN - NLM
STAT- MEDLINE
DCOM- 20021016
LR  - 20161124
IS  - 1062-936X (Print)
IS  - 1026-776X (Linking)
VI  - 13
IP  - 1
DP  - 2002 Mar
TI  - Mechanism based structure-activity relationships for skin sensitisation--the 
      carbonyl group domain.
PG  - 145-52
AB  - The biological activity of skin-sensitising chemicals is related to their ability 
      to react either directly or after metabolic activity with appropriate skin 
      proteins. For direct-acting electrophilic compounds, this ability can be modelled 
      by the Relative Alkylation Index (RAI) by a combination of electrophilicity and 
      hydrophobicity parameters. Several SARs based on this approach are reported. In 
      this present work, electrophilicity parameters based on Taft substituent 
      constants are used together with Leo and Hansch log P fragment values to 
      calculate RAI values for hard electrophiles having a reactive carbonyl group. 
      These are then applied to analysis of sensitisation data obtained in the murine 
      Local Lymph Node Assay (LLNA) for two series of diketones as well as a homologous 
      series of alpha, beta-unsaturated aldehydes. The sensitisation potentials of 
      these reactive electrophiles show good correlations with the RAI. These findings 
      re-affirm the view that physicochemical parameters are the key to eliciting the 
      relationship between chemical structure and a toxic endpoint. They provide 
      further evidence of the value of SAR studies in identifying mechanisms of 
      sensitisation and aiding risk assessments without the need for extensive animal 
      testing.
FAU - Roberts, D W
AU  - Roberts DW
AD  - Unilever Research Port Sunlight, Bebbington, Wirral, UK. 
      david.w.roberts@unilever.com
FAU - Patlewicz, G
AU  - Patlewicz G
LA  - eng
PT  - Journal Article
PL  - England
TA  - SAR QSAR Environ Res
JT  - SAR and QSAR in environmental research
JID - 9440156
RN  - 0 (Aldehydes)
RN  - 0 (Ketones)
RN  - 7440-44-0 (Carbon)
SB  - IM
MH  - Aldehydes/adverse effects/*chemistry
MH  - Carbon/chemistry
MH  - Chemical Phenomena
MH  - Chemistry, Physical
MH  - Dermatitis, Contact/*etiology
MH  - Immunization
MH  - Ketones/chemistry
MH  - Structure-Activity Relationship
EDAT- 2002/06/21 10:00
MHDA- 2002/10/17 04:00
CRDT- 2002/06/21 10:00
PHST- 2002/06/21 10:00 [pubmed]
PHST- 2002/10/17 04:00 [medline]
PHST- 2002/06/21 10:00 [entrez]
AID - 10.1080/10629360290002244 [doi]
PST - ppublish
SO  - SAR QSAR Environ Res. 2002 Mar;13(1):145-52. doi: 10.1080/10629360290002244.