Alarms about structural alerts

Green Chemistry : an International Journal and Green Chemistry Resource : GC
Vinicius AlvesAlexander Tropsha

Abstract

Structural alerts are widely accepted in chemical toxicology and regulatory decision support as a simple and transparent means to flag potential chemical hazards or group compounds into categories for read-across. However, there has been a growing concern that alerts disproportionally flag too many chemicals as toxic, which questions their reliability as toxicity markers. Conversely, the rigorously developed and properly validated statistical QSAR models can accurately and reliably predict the toxicity of a chemical; however, their use in regulatory toxicology has been hampered by the lack of transparency and interpretability. We demonstrate that contrary to the common perception of QSAR models as "black boxes" they can be used to identify statistically significant chemical substructures (QSAR-based alerts) that influence toxicity. We show through several case studies, however, that the mere presence of structural alerts in a chemical, irrespective of the derivation method (expert-based or QSAR-based), should be perceived only as hypotheses of possible toxicological effect. We propose a new approach that synergistically integrates structural alerts and rigorously validated QSAR models for a more transparent and accurate safety ...Continue Reading

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Citations

Dec 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Piotr MinkiewiczMałgorzata Darewicz
Jun 21, 2017·Green Chemistry : an International Journal and Green Chemistry Resource : GC·Vinicius M AlvesAlexander Tropsha
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