Single or mixture halogenated chemicals? Risk assessment and developmental toxicity prediction on zebrafish embryos based on weighted descriptors approach

Halogenated chemicals including perfluoroalkyl substances (PFASs) represent an emerging class of endocrine-disrupting pollutants for human populations across the globe. Distress related to their environmental fate and toxicity has initiated several research projects, but the amount of experimental data available for these pollutants is limited. The objective of this study is to assess the toxicity of potentially “safer” alternatives, in relation to their existing counterparts. Developmental toxicity data on zebrafish (Danio rerio) embryos of single and tertiary halogenated mixtures were modeled employing quantitative structure-toxicity relationship (QSTR) tool. The computed models are then employed for toxicity prediction of theoretically generated binary and tertiary mixtures (which have no experimental data) to check their possible threshold and mode of toxicity for future risk assessment. Further, for toxicity screening, we have prepared a huge external dataset consists of single (24), binary (276) and tertiary (2024) mixtures of PFASs. It was accomplished by combination method and predicted through developed models for interpretation of toxicity threats for individuals and mixtures along with identification of diverse range and combination of toxicity thresholds. We found that chemicals in mixtures displayed concentration addition of individual chemical suggesting a similar mode of toxic action and non-interaction of chemicals. Not only that, mixtures of halogenated compounds including PFASs showed less toxicity than their single counterparts and the obtained toxicity trend is: Single chemical > Binary mixture > Tertiary mixture.