PMID- 10416702
OWN - NLM
STAT- MEDLINE
DCOM- 19990908
LR  - 20190721
IS  - 0105-1873 (Print)
IS  - 0105-1873 (Linking)
VI  - 41
IP  - 1
DP  - 1999 Jul
TI  - Structure-activity relationships in the murine local lymph node assay for skin 
      sensitization: alpha,beta-diketones.
PG  - 14-7
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. Several structure-activity 
      relationships based on this approach have been reported, but most of them cover 
      guinea pig sensitization test data on what chemists would classify as relatively 
      soft electrophilic chemicals. In the present work, an electrophilicity parameter 
      based on Taft substituent constants is derived for hard electrophiles having a 
      reactive carbonyl group, and is used to calculate RAI values for the analysis of 
      sensitization test data obtained in the murine local lymph node assay (LLNA) for 
      a series of alpha, beta-diketones. The sensitization potential of these reactive 
      hard electrophilic carbonyl compounds in the LLNA shows a good correlation with 
      the RAI. Overall, the findings reaffirm our view that physical organic chemistry 
      is the key to understanding why some chemicals sensitize more strongly than 
      others, while some do not sensitize at all, and provide further evidence of the 
      value of the LLNA for SAR studies.
FAU - Roberts, D W
AU  - Roberts DW
AD  - Unilever Research Port Sunlight, Wirral, Merseyside, UK.
FAU - York, M
AU  - York M
FAU - Basketter, D A
AU  - Basketter DA
LA  - eng
PT  - Journal Article
PL  - England
TA  - Contact Dermatitis
JT  - Contact dermatitis
JID - 7604950
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Ketones)
SB  - IM
MH  - Animals
MH  - Carbonic Anhydrase Inhibitors/*chemistry
MH  - Culture Techniques
MH  - *Immunization
MH  - Ketones/*chemistry
MH  - Lymph Nodes/*immunology
MH  - Mice
MH  - Sensitivity and Specificity
MH  - Skin Tests/methods
MH  - Structure-Activity Relationship
EDAT- 1999/07/23 00:00
MHDA- 1999/07/23 00:01
CRDT- 1999/07/23 00:00
PHST- 1999/07/23 00:00 [pubmed]
PHST- 1999/07/23 00:01 [medline]
PHST- 1999/07/23 00:00 [entrez]
AID - 10.1111/j.1600-0536.1999.tb06201.x [doi]
PST - ppublish
SO  - Contact Dermatitis. 1999 Jul;41(1):14-7. doi: 10.1111/j.1600-0536.1999.tb06201.x.