PMID- 16978028
OWN - NLM
STAT- MEDLINE
DCOM- 20061113
LR  - 20220311
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 19
IP  - 9
DP  - 2006 Sep
TI  - Mechanistic applicability domains for non-animal based prediction of 
      toxicological endpoints. QSAR analysis of the schiff base applicability domain 
      for skin sensitization.
PG  - 1228-33
AB  - Several recent (1999 onward) publications on skin sensitization to aldehydes and 
      ketones, which can sensitize by covalent binding to skin protein via Schiff base 
      formation, present QSARs based on the Taft sigma parameter to model reactivity 
      and log P to model hydrophobicity. Here, all of the data are reanalyzed together 
      in a stepwise self-consistent way using the parameters log P (octanol/water) and 
      Sigmasigma, the latter being the sum of Taft sigma values for the two groups R 
      and R' in RCOR'. A QSAR is derived: pEC3 = 1.12(+/-0.07) Sigmasigma + 
      0.42(+/-0.04) log P - 0.62(+/-0.13); n = 16 R(2) = 0.952 R(2)(adj) = 0.945 s = 
      0.12 F = 129.6, based on mouse local lymph node assay (LLNA) data for 11 
      aliphatic aldehydes, 1 alpha-ketoester and 4 alpha,beta-diketones. In developing 
      this QSAR, an initial regression equation for a training set of 10 aldehydes was 
      found to predict a test set consisting of the other 6 compounds. The QSAR is 
      found to be well predictive for LLNA data on a series of alpha,gamma-diketones 
      and also correctly predicts the nonsensitizing properties of simple 
      dialkylketones. It is shown to meet all of the criteria of the OECD principles 
      for applicability within regulatory practice. In view of the structural diversity 
      within the sets of compounds considered here, the present findings confirm the 
      view that within the mechanistic applicability domain the differences in 
      sensitization potential are dependent solely on differences in chemical 
      reactivity and partitioning.
FAU - Roberts, David W
AU  - Roberts DW
AD  - School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, 
      Liverpool L3 3AF, England. d.w.roberts@ljmu.ac.uk
FAU - Aptula, Aynur O
AU  - Aptula AO
FAU - Patlewicz, Grace
AU  - Patlewicz G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Benzaldehydes)
RN  - 0 (Ketones)
RN  - 0 (Schiff Bases)
RN  - 0 (atranol)
RN  - 0 (chloroatranol)
RN  - 1HG84L3525 (Formaldehyde)
RN  - T3C89M417N (Glutaral)
SB  - IM
MH  - Benzaldehydes/chemistry/toxicity
MH  - Formaldehyde/chemistry/toxicity
MH  - Glutaral/chemistry/toxicity
MH  - Ketones/chemistry/toxicity
MH  - Quantitative Structure-Activity Relationship
MH  - Schiff Bases/*chemistry
MH  - Skin/*drug effects
MH  - *Toxicity Tests
EDAT- 2006/09/19 09:00
MHDA- 2006/11/14 09:00
CRDT- 2006/09/19 09:00
PHST- 2006/09/19 09:00 [pubmed]
PHST- 2006/11/14 09:00 [medline]
PHST- 2006/09/19 09:00 [entrez]
AID - 10.1021/tx060102o [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2006 Sep;19(9):1228-33. doi: 10.1021/tx060102o.