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In chemico toxicity approaches to assess, identify and prioritize contaminants in water

Nature Water volume 3, pages 854–866 (2025)Cite this article

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Abstract

Water quality assessment is exceedingly challenging given the complexity of the anthropogenic chemicals present in the environment. In addition, water treatment is increasingly reliant on chemical oxidants, which transform natural and anthropogenic organic compounds into a wide spectrum of transformation products with unknown toxicities. Existing strategies to evaluate the toxicity of these complex mixtures have so far primarily focused on the application of in vitro assays. Existing in vitro assays provide useful insights into the adverse outcomes for a variety of toxicological endpoints but generally do not provide information about the identities of the toxicant(s) responsible for the observed effect in environmental samples. Advancements in in vitro assays combined with non-targeted analysis show substantial progress in identifying emerging chemicals of concern, albeit with selection biases for analytes that are compatible with sample extraction and preparation approaches. Here we discuss the application of molecular toxicology (in chemico) approaches as a promising complement to in vitro assays to assess water quality and responsible toxicants. These in chemico approaches show particular promise for compounds that are challenging to extract and detect using conventional approaches, such as those that are highly polar, reactive (for example, organic electrophiles) and/or volatile compounds. We structure the discussion of the different in chemico approaches around the molecular initiating event, which is the initial step of the adverse outcome pathway that describes the molecular-level interactions between toxicants and organisms. In chemico approaches that use biomolecules of different complexities to investigate covalent and non-covalent interactions with contaminants are highlighted. This includes in chemico studies focusing on (1) the assessment of individual contaminants, (2) the overall toxicity of samples from laboratory studies or the environment and (3) the identification of toxicants in complex (environmental) mixtures. Major advancements in each of these areas are discussed, and future major research needs are outlined.

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Fig. 1: Overview of the AOP concept.
Fig. 2: Biomolecular probes for in chemico toxicity assessments of water contaminants.
Fig. 3: Examples of covalent/non-covalent binding mechanisms.

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Acknowledgements

This study was supported by the US National Science Foundation (CAREER award 2143152) and the US Environmental Protection Agency (R840605). D.N.G. was supported by a National Science Foundation Graduate Research Fellowship under grant no. DGE2139757, and A.R. acknowledges financial support from Johns Hopkins University through the Vivien Thomas Scholars Initiative.

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  1. Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA

    Daisy N. Grace, Alyssa Rorie & Carsten Prasse

  2. Risk Sciences and Policy Institute, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Carsten Prasse

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Grace, D.N., Rorie, A. & Prasse, C. In chemico toxicity approaches to assess, identify and prioritize contaminants in water. Nat Water 3, 854–866 (2025). https://doi.org/10.1038/s44221-025-00468-x

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