Issue 24, 2016

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

Abstract

Skin sensitization is a major environmental and occupational health hazard. Although many chemicals have been evaluated in humans, there have been no efforts to model these data to date. We have compiled, curated, analyzed, and compared the available human and LLNA data. Using these data, we have developed reliable computational models and applied them for the virtual screening of chemical libraries to identify putative skin sensitizers. The overall concordance between murine LLNA and human skin sensitization responses for a set of 135 unique chemicals was low (R = 28–43%), although several chemical classes had high concordance. We have succeeded to develop predictive QSAR models of all available human data with the external correct classification rate of 71%. A consensus model integrating concordant QSAR predictions and LLNA results afforded a higher CCR of 82% but at the expense of the reduced external dataset coverage (52%). We used the developed QSAR models for the virtual screening of the CosIng database and identified 1061 putative skin sensitizers; for seventeen of these compounds, we found published evidence of their skin sensitization effects. Models reported herein provide more accurate alternatives to LLNA testing for human skin sensitization assessment across diverse chemical data. In addition, they can also be used to guide the structural optimization of toxic compounds to reduce their skin sensitization potential.

Graphical abstract: QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

Supplementary files

Article information

Article type
Paper
Submitted
06 Jul 2016
Accepted
06 Oct 2016
First published
06 Oct 2016

Green Chem., 2016,18, 6501-6515

QSAR models of human data can enrich or replace LLNA testing for human skin sensitization

V. M. Alves, S. J. Capuzzi, E. N. Muratov, R. C. Braga, T. E. Thornton, D. Fourches, J. Strickland, N. Kleinstreuer, C. H. Andrade and A. Tropsha, Green Chem., 2016, 18, 6501 DOI: 10.1039/C6GC01836J

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements