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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...

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Bibliographic Details
Published in:Chemical research in toxicology 2017-06, Vol.30 (6), p.1309-1316
Main Authors: Roberts, David W, Schultz, Terry W, Api, Anne Marie
Format: Article
Language:English
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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