Introduction to the “Tracking complex mixtures of chemicals in human- and eco-exposome: the nexus of models, analytics, and toxicity” themed issue

We live in a chemical-intensive world where the number and volume of substances on the market are constantly growing. Exposure to cocktails of these chemicals can be associated with adverse effects on human health and ecosystems. This themed issue assembles contributions that reflect the state of the art and ongoing and future focus on evaluating the exposure and risk associated with tens of thousands of chemical contaminants, including computational exposure science and toxicology, exposomics, bioassay-based toxicity screening, non-targeted chemical analysis, and analysis of mixtures and substances of unknown or variable composition.

Two articles in this themed issue have focused on the targeted and non-targeted analysis of complex mixtures of chemicals in the environment. Elapavalore & Schymanski et al. (https://doi.org/10.1039/D2EM00349J) described new efforts to contribute spectra relevant for exposomics to the open mass-spectral library MassBank (https://www.massbank.eu) using various open-source software tools, including the R packages RMassBank and Shinyscreen. More than 5000 spectra from 783 of the 1268 compounds from the US Environmental Protection Agency Non-Targeted Analysis Collaborative Trial (ENTACT) were added to MassBank. This mass-spectra database is likely to facilitate the identification of known and unknown chemicals in complex environmental or biological samples. In another study, with high-resolution mass spectrometry, Kim et al. (https://doi.org/10.1039/D2EM00349J) identified over 20 emerging polyfluoroalkyl substances in rainwater samples from seven U.S. sites. Their work has revealed the prevalence of branched polyfluorinated carboxylic acids in rainwater and underscores the importance of evaluating previously unappreciated chemicals that are beyond the current analyte lists. To address the prioritization of large numbers of features in the non-target analysis, Zhang et al. (https://doi.org/10.1039/D3EM00317E) have proposed a strategy that can rank chemical features detected in dust samples based on a model-derived metric that quantifies a feature's attribute to certain concerns of a chemical (e.g., bioaccumulation potential).

Three studies in this themed issue have combined chemical analysis, in vitro bioassays, and mixture toxicity models to explain the effect of chemical mixtures in certain targeted toxicological endpoints. Reiter et al. (https://doi.org/10.1039/D3EM00033H) and Escher et al. (https://doi.org/10.1039/D3EM00076A) applied passive equilibrium sampling with silicone in organs and blubber of marine mammals to transfer environmental mixtures of chemicals into an extract without changing their composition. The combination of in vitro bioassays and chemical profiling of legacy and emerging contaminants helps understand how the mixtures cause the activation of cellular toxicity pathways. The mixture effects predicted from the quantified chemical concentrations explained most of the activation of the aryl hydrocarbon receptor triggered by the extracts, but only a fraction of the activation of the oxidative stress response (AREc32) and the peroxisome-proliferator activated receptor (PPARγ), suggesting more unknown compounds are contributing to the mixture effect. In another study by Zhang et al (https://doi.org/10.1039/D3EM00182B), multiple chemical analysis was conducted for both dust and pet hair and in vitro data from ToxCast were used to characterize the health risks of indoor emerging pollutants.

In terms of mixture toxicity, two studies have worked on the experimental and meta-analysis of chemicals with different combinations. In one study, Lalwani et al. (https://doi.org/10.1039/D3EM00188A) reported the increased toxicity of Pb²⁺ in combination with two mechanistically different mitochondrial toxicants, whereby they advocate the evaluation of co-exposures to protect human and ecosystem health. In another study, Mehta et al. (https://doi.org/10.1039/D3EM00069A) mined the mixture-toxicity research in the entire body of published literature and identified priority chemicals that overlapped only with a small fraction of the chemical space of the European chemical regulation REACH.

This themed issue also contains a manuscript on the fate and transport of environmental mixtures. Gao et al. (https://doi.org/10.1039/D2EM00466F) developed a fundamental model for calculating interfacial adsorption of complex ionic and nonionic per- and polyfluoroalkyl substance (PFAS) mixtures in the presence of mixed salts, providing interfacial partitioning predictions for systems with PFAS mixtures as well as systems with salts of multiple valencies and concentrations. This can provide valuable prediction models on the equilibrium of PFAS mixtures among different environmental matrices.

We hope that you enjoy this collection of papers focused on the exposure and toxicity of chemical mixtures. We are grateful to all authors who contributed their work to this themed issue and to the reviewers, associate editors, editorial board, and staff who aided in bringing this collection together.

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