Evidence-based assessment on environmental mixture using a concentration-dependent transcriptomics approach. (October 2020)

• Record Type: Journal Article
• Authors: Wang, Pingping; Xia, Pu; Wang, Zhihao; Zhang, Xiaowei
• Is Part Of: Environmental pollution. Volume 265(2020)Part A
• Publication Date: 2020-10
• Subjects: Mixture toxicity -- Effect-based methods -- Component-based approach -- Pathway-based analysis; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2020.114839
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Development of new approach methodologies is urgently needed to characterize the likelihood that complex mixtures of chemicals affect water quality. Omics advances in ecotoxicology allow assessment on a broadest coverage of disrupted biological pathway by mixtures. Here the usefulness of transcriptomic analyses for evaluation of combined effects and identification of main effect components are explored. Two artificial mixtures (Mix 1 and Mix 2) were tested by a concentration-dependent reduced zebrafish transcriptome (CRZT) approach and toxicity bioassays using zebrafish embryos. Then, the toxicities and transcriptomic effects of 12 component chemicals on embryos were incorporated into additivity models to characterize the combined effects of chemicals in mixtures and to identify the main bioactive compounds. Mix 1 and Mix 2 displayed similar embryo toxicities (LD50 : 6.6 μM and 8.7 μM, respectively), however, Mix 2 elicited broader biological process perturbations and 5-fold higher transcriptome potency (point of departure eliciting a 20% pathway response, PODpath20 ) than Mix 1. The predicted mixture toxicities derived from additivity expectations deviated by 2-fold or less from the measured embryo toxicities except for the Jaw defect endpoint; most biological processes deviated by 3-fold or less. Finally, diclofenac (DFC) and propiconazole (PCZ) were identified as the main contributing components (≥80% explanation) to the embryo toxicity and biological process perturbations by Mix 1. While DFC and chlorophene (CLP) explained up to 80% of the embryo toxicities and biological effects of Mix 2 associated with development and Metabolism processes. The CRZT approach provides a powerful tool for assessment of biological pathways perturbed by chemicals in mixtures and for identification of main bioactive compounds. Graphical abstract: Image 1 Highlights: CA and IA models could predict potency of mortality and transcriptome responses. Specific biological processes of two mixtures were predictable by additivity models. Concentration dependent transcriptome effectively identified main effect components. Abstract : The CRZT approach provides a powerful tool for characterizing the effects of complex chemical mixtures.