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Environ Sci Technol ; 56(12): 8363-8372, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35561338

RESUMO

Data on toxic effects are at large missing the prevailing understanding of the risks of industrial chemicals. Thyroid hormone (TH) system disruption includes interferences of the life cycle of the thyroid hormones and may occur in various organs. In the current study, high-throughput screening data available for 14 putative molecular initiating events of adverse outcome pathways, related to disruption of the TH system, were used to develop 19 in silico models for identification of potential thyroid hormone system-disrupting chemicals. The conformal prediction framework with the underlying Random Forest was used as a wrapper for the models allowing for setting the desired confidence level and controlling the error rate of predictions. The trained models were then applied to two different databases: (i) an in-house database comprising xenobiotics identified in human blood and ii) currently used chemicals registered in the Swedish Product Register, which have been predicted to have a high exposure index to consumers. The application of these models showed that among currently used chemicals, fewer were overall predicted as active compared to chemicals identified in human blood. Chemicals of specific concern for TH disruption were identified from both databases based on their predicted activity.


Assuntos
Disruptores Endócrinos , Simulação por Computador , Disruptores Endócrinos/toxicidade , Ensaios de Triagem em Larga Escala , Humanos , Hormônios Tireóideos/metabolismo , Xenobióticos
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