PMID- 10727166
OWN - NLM
STAT- MEDLINE
DCOM- 20000424
LR  - 20190721
IS  - 0105-1873 (Print)
IS  - 0105-1873 (Linking)
VI  - 42
IP  - 3
DP  - 2000 Mar
TI  - Quantitative structure-activity relationships: sulfonate esters in the local 
      lymph node assay.
PG  - 154-61
AB  - The biological activity of skin-sensitizing chemicals is related to their ability 
      to react, either directly or after metabolic activation, with appropriate skin 
      proteins. For direct acting electrophilic compounds, this ability can be 
      modelled, using the RAI (relative alkylation index) approach, by a combination of 
      electrophilicity and hydrophobicity parameters. The development of predictive 
      quantitative structure-activity relationships (QSAR) models of skin 
      sensitization, using mechanism-based physicochemical parameters, has been greatly 
      facilitated by the introduction of the murine local lymph node assay (LLNA), 
      which is able to describe the extent of the biological response in objective and 
      quantitative terms. In the present work, sensitization response data in the LLNA 
      is generated for a series of 6 sulfonate esters. An RAI-based hybrid 
      QSAR/dose-response relationship is derived using a negative hydrophobicity 
      coefficient in the RAI expression, to model the effect of retention of the 
      hydrophobic test chemicals in the stratum corneum. Dose-response analyses are 
      used to estimate EC3 and EC20 values as quantitative indices of skin 
      sensitization potential for each compound, and regression analysis is applied to 
      develop QSARs correlating these EC3 and EC20 values with an RAI-based parameter. 
      The high statistical quality of these QSARs demonstrates both the consistency of 
      the LLNA method for generating high quality skin sensitization data, and the 
      value of the RAI approach in development of mathematical models for skin 
      sensitization.
FAU - Roberts, D W
AU  - Roberts DW
AD  - Unilever Research, Port Sunlight, Bebington, Wirral, UK.
FAU - Basketter, D A
AU  - Basketter DA
LA  - eng
PT  - Journal Article
PL  - England
TA  - Contact Dermatitis
JT  - Contact dermatitis
JID - 7604950
RN  - 0 (Esters)
RN  - 0 (Sulfonic Acids)
SB  - IM
MH  - Alkylation
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Esters/*analysis/pharmacology
MH  - Female
MH  - Lymph Nodes/*chemistry
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Structure-Activity Relationship
MH  - Sulfonic Acids/*analysis/pharmacology
EDAT- 2000/03/22 09:00
MHDA- 2000/04/29 09:00
CRDT- 2000/03/22 09:00
PHST- 2000/03/22 09:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 2000/03/22 09:00 [entrez]
AID - 10.1034/j.1600-0536.2000.042003154.x [doi]
PST - ppublish
SO  - Contact Dermatitis. 2000 Mar;42(3):154-61. doi: 
      10.1034/j.1600-0536.2000.042003154.x.