Predicting skin sensitization potency for Michael acceptors in the LLNA using quantum mechanics calculations.
Chem Res Toxicol
; 26(5): 767-74, 2013 May 20.
Article
en En
| MEDLINE
| ID: mdl-23611145
ABSTRACT
This study outlines the development of a series of quantitative mechanistic models enabling skin sensitization potency in the LLNA to be predicted for direct acting Michael acceptors. These models utilized several computational descriptors based on knowledge of the Michael addition reaction mechanism. The key descriptor was calculated using density functional theory and modeled the stability of the reaction intermediate. A second descriptor relating to the available surface area at the site of the reaction was also found to be important. Several poorly predicted compounds were identified, and in all cases, these could be rationalized mechanistically. The analysis of these compounds allowed a well-defined mechanistically driven applicability domain to be developed. The study showed that in silico quantitative mechanistic models, with a well-defined applicability domain, can be used to predict skin sensitization potency in the LLNA. The approach presented has the potential to be of use as part of a weight of evidence approach for predicting skin sensitization without the use of animals in risk assessment.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Compuestos Orgánicos
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Teoría Cuántica
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Alérgenos
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Ensayo del Nódulo Linfático Local
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Pruebas de Irritación de la Piel
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Chem Res Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2013
Tipo del documento:
Article