Application of Biomarker Tools Using Bivalve Models Toward the Development of Adverse Outcome Pathways for Contaminants of Emerging Concern

Abstract

As contaminant exposures in aquatic ecosystems continue to increase, the need for streamlining research efforts in environmental toxicology using predictive frameworks also grows. One such framework is the adverse outcome pathway (AOP). An AOP framework organizes and utilizes toxicological information to connect measurable molecular endpoints to an adverse outcome of regulatory relevance via a series of events at different levels of biological organization. Molecular endpoints or biomarkers are essential to develop AOPs and are valuable early warning signs of the toxicity of pollutants, including contaminants of emerging concern. Ecological risk-assessment approaches using tools such as biomarkers and AOPs benefit from identification of molecular targets conserved across species. Bivalve models are useful in such approaches and integral to our understanding of ecological and human health risks associated with contaminant exposures. We discuss the value of using biomarker approaches in bivalve models to meet the demands of twenty-first-century toxicology.

Daphnia as a model organism to probe biological responses to nanomaterials—from individual to population effects via adverse outcome pathways

“…These interlinked pathways can be assembled into AOPs and serve as a foundation for the development of a mechanistic understanding of toxicity and disease. Therefore, AOPs play an essential role in the ecological risk assessment of environmental contaminants (Ankley et al, 2010;Khan et al, 2020).…”

Challenges and Opportunities for Integrating In Silico Models and Adverse Outcomes Pathways to Set and Relate New Biomarkers

“…Using the AOP framework, Khan et al (2020) showed that early events on molecular levels can be connected to important effects on bivalves organisms, which can be used as relevant biomarkers for the assessment of environmental risk related to the presence of contaminants of emerging concern [16].…”

Metformin-Induced Epigenetic Toxicity in Zebrafish: Experimental and Molecular Dynamics Simulation Studies

“…Therefore, it may be a valuable early toxicological warning signal to recognize and identify biomarkers before those irreversible abnormalities. Molecular biomarkers, such as DNA methylation, histone modification, chromatin remodeling, and noncoding RNA related to epigenetic methods, have received widespread attention as early warning indicators of pollutant exposure. , Among these factors, DNA methylation can change the homeostasis of the genome, leading to conformational changes in chromatin DNA, alterations in DNA stability, and the abnormal expression of structural and functional proteins. These changes will cause normal cell cycle inhibition, abnormal differentiation, and cell apoptosis. , To date, environmental contaminants, including trace elements, persistent organic pollutants (POPs), and endocrine disruptors (EDCs) have been found to induce DNA methylation via in vitro and in vivo assays. , These results indicate that DNA methylation may be an important biomarker of environmental chemical exposure and consequent changes to the aquatic ecosystem. − …”

“…Molecular biomarkers, such as DNA methylation, histone modification, chromatin remodeling, and noncoding RNA related to epigenetic methods, have received widespread attention as early warning indicators of pollutant exposure. 16,17 Among these factors, DNA methylation can change the homeostasis of the genome, leading to conformational changes in chromatin DNA, alterations in DNA stability, and the abnormal expression of structural and functional proteins. These changes will cause normal cell cycle inhibition, abnormal differentiation, and cell apoptosis.…”