Environmental surveillance and monitoring—The next frontiers for high‐throughput toxicology

Abstract

High-throughput toxicity testing technologies along with the World Wide Web are revolutionizing both generation of and access to data regarding the biological activities that chemicals can elicit when they interact with specific proteins, genes, or other targets in the body of an organism. To date, however, most of the focus has been on the application of such data to assessment of individual chemicals. The authors suggest that environmental surveillance and monitoring represent the next frontiers for high-throughput toxicity testing. Resources already exist in curated databases of chemical-biological interactions, including highly standardized quantitative dose-response data generated from nascent high-throughput toxicity testing programs such as ToxCast and Tox21, to link chemicals detected through environmental analytical chemistry to known biological activities. The emergence of the adverse outcome pathway framework and the associated knowledge base for linking molecular-level or pathway-level perturbations of biological systems to adverse outcomes traditionally considered in risk assessment and regulatory decision-making through a series of measurable biological changes provides a critical link between activity and hazard. Furthermore, environmental samples can be directly analyzed via high-throughput toxicity testing platforms to provide an unprecedented breadth of biological activity characterization that integrates the effects of all compounds present in a mixture, whether known or not. Novel application of these chemical-biological interaction data provides an opportunity to transform scientific characterization of potential hazards associated with exposure to complex mixtures of environmental contaminants.

When Are Adverse Outcome Pathways and Associated Assays “Fit for Purpose” for Regulatory Decision‐Making and Management of Chemicals?

“…Assay identification and development for use in environmental monitoring activities. Assays based on KEs from AOPs are also being identified and developed for environmental monitoring purposes (Schroeder et al 2016). For example, the SOLUTIONS project (Helmholtz Centre for Environmental Research 2019) in the European Union focuses on assembling a battery of assays for water quality monitoring and chemical assessments (Neale et al 2017).…”

An integrated approach for identifying priority contaminant in the Great Lakes Basin – Investigations in the Lower Green Bay/Fox River and Milwaukee Estuary areas of concern

“…In conjunction with the targeted biological effects measurements, we employed two prior knowledge approaches for bio-effect predictions (Schroeder et al, 2016) based on site-specific chemistry data. One approach uses a publicly available in vivo chemical interaction source, the CTD.…”

“…This database was used to identify genes and associated pathways potentially impacted by chemicals detected in the environmental samples. Specifically, the list of chemicals detected at each site was uploaded to the CTD, which was followed by a batch query, extracting all gene targets with reported interactions with those chemicals from the database (Schroeder et al 2016).…”

“…Untargeted approaches such as "omics" measurements in fish tissues (e.g., Berninger et al, 2014;Garcia-Reyero et al, 2011;Martinovic-Weigelt et al, 2014;Skelton et al, 2014) and analysis of water samples or extracts using batteries of pathway-based in vitro assays (Escher et al, 2014;Schroeder et al, 2016) are an important complement to supervised measurements when, as typically is the case with environmental samples, unknown/unmeasured contaminants are of concern. Untargeted approaches ideally assess activities of contaminants without bias for any specific biological pathways, which is especially important for surveillance efforts (Ekman et al 2013;Escher et al 2014;Schroeder et al 2016).…”

Uncertainties of testing methods: What do we (want to) know about carcinogenicity?

“…One of the most important goals is to increase the testing throughput in order to improve -the availability of regulatory test data for many chemicals, -the effectiveness of substitution of the more hazardous chemicals by providing reliable data for an ample set of potential alternative chemicals, also in the low tonnage production range or even for green chemical engineering (Maertens et al, 2014), -the assessment of mixture toxicity, -the assessment of environmental media including the use of bio-analytics to complement chemical analytics (Schroeder et al, 2016), -approaches to cross-species extrapolation for ample coverage of environmental toxicity (Groh et al, 2015), -the assessment of the multitude of nanomaterial compositions, forms and size distributions, -the possibility to retest chemicals according to progress in the development of scientific and toxicological understanding. In addition to these practical needs, a critical mass of concern regarding the scientific uncertainties of animal test results and their regulatory utility also has been steadily accumulating in recent years (e.g., Basketter et al, 2012;Paparella et al, 2013;Hartung, 2013;Leist et al, 2014;NAS, 2015).…”