Loading…
Skin Sensitization QMM for HRIPT NOEL Data: Aldehyde Schiff-Base Domain
The general chemistry principles underlying skin sensitization for Schiff base (SB) electrophiles may be used to develop a quantitative mechanistic model (QMM), based on reactivity supplemented with a hydrophobicity parameter for some but not all structures within the SB reaction domain. For aliphat...
Saved in:
Published in: | Chemical research in toxicology 2017-06, Vol.30 (6), p.1309-1316 |
---|---|
Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | The general chemistry principles underlying skin sensitization for Schiff base (SB) electrophiles may be used to develop a quantitative mechanistic model (QMM), based on reactivity supplemented with a hydrophobicity parameter for some but not all structures within the SB reaction domain. For aliphatic Schiff base electrophiles, the log of the no observed effect level (NOEL) values (pNOEL) from the human repeated insult patch test (HRIPT) can be calculated by the reactivity parameter summation of sigma star values (Σσ*) and a hydrophobicity parameter (logP). Specifically, the QMM, pNOEL = 2.34(±0.33) Σσ* + 0.19(±0.07) logP – 2.62(±0.22), n = 19, R 2 = 0.77, R 2 (adj) = 0.74, s = 0.20, F = 27, was developed. Not all parts of the Schiff base domain are modeled with one equation. Particularly, predicting aromatic aldehydes and ketones appears to require a separate equation. Interestingly, the same physical organic chemical properties originally applied to modeling the local lymph node assay potency of Schiff base electrophiles apply to human potency as represented by the HRIPT. |
---|---|
ISSN: | 0893-228X 1520-5010 |
DOI: | 10.1021/acs.chemrestox.7b00050 |