Structural alerts for the identification of bioaccumulative compounds

Legislators have included bioaccumulation in the evaluation of chemicals in the framework of the European Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation. REACH requires information on the bioconcentration factor (BCF), which is a parameter for assessing bioaccumulation and encourages the use of a weight-of-evidence approach, including predictions from quantitative structure-activity relationships (QSARs). This study presents a novel approach, based on structural alerts, to be used as a decision-support system for the identification of substances with bioaccumulation potential. In a regulatory framework, these alerts can be integrated with other sources of information, such as experimental and in silico data, to reduce the uncertainty of the assessment, thereby supporting a weight-of-evidence approach. Moreover, the identified alerts have a direct connection with relevant structural features, thus fostering the applicability and interpretability of the approach. The structural alerts were identified on 779 chemicals annotated for their fish BCF, and the approach was then validated on 278 external molecules. The developed decision-support system allowed identification of 77% of bioaccumulative chemicals and was competitive with more complex QSAR models used in regulatory assessments. The approach is implemented in an easy-to-use workflow, provided free of charge. Integr Environ Assess Manag 2019;15:19-28. © 2018 SETAC.

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