Big Question to Developing Solutions: A Decade of Progress in the Development of Aquatic New Approach Methodologies from 2012 to 2022

Abstract

In 2012, 20 key questions related to hazard and exposure assessment and environmental and health risks of pharmaceuticals and personal care products in the natural environment were identified. A decade later, this article examines the current level of knowledge around one of the lowest‐ranking questions at that time, number 19: “Can nonanimal testing methods be developed that will provide equivalent or better hazard data compared with current in vivo methods?” The inclusion of alternative methods that replace, reduce, or refine animal testing within the regulatory context of risk and hazard assessment of chemicals generally faces many hurdles, although this varies both by organism (human‐centric vs. other), sector, and geographical region or country. Focusing on the past 10 years, only works that might reasonably be considered to contribute to advancements in the field of aquatic environmental risk assessment are highlighted. Particular attention is paid to methods of contemporary interest and importance, representing progress in (1) the development of methods which provide equivalent or better data compared with current in vivo methods such as bioaccumulation, (2) weight of evidence, or (3) ‐omic‐based applications. Evolution and convergence of these risk assessment areas offer the basis for fundamental frameshifts in how data are collated and used for the protection of taxa across the breadth of the aquatic environment. Looking to the future, we are at a tipping point, with a need for a global and inclusive approach to establish consensus. Bringing together these methods (both new and old) for regulatory assessment and decision‐making will require a concerted effort and orchestration. Environ Toxicol Chem 2023;00:1–15. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Pharmaceuticals and Personal Care Products in the Environment: What Progress Has Been Made in Addressing the Big Research Questions?

“…Work on PPCPs in the coming decade will benefit from a wide range of "new" methodologies that are introduced in papers in the special issue. These include citizen science to monitor PPCPs (Wilkinson et al, 2024); non-invasive monitoring tools for monitoring uptake into and effects on organisms (Bean et al, 2024); new approach methodologies that minimize the use of animals (Ankley et al, 2024;Bean et al, 2024;Langan et al, 2024); genetic modification methods, such as clustered, regularly interspaced short palindromic repeats, coupled with new imaging methods (Margiotta-Casaluci et al, 2024); omics methods (Brooks et al, 2024;Manaia et al, 2024); high-throughput experimental testing methods-for example, high-throughput absorption, distribution, metabolism, and excretion tests (ADME; Kidd et al, 2024;Margiotta-Casaluci et al, 2024); machine learning approaches (Carter et al, 2024;Margiotta-Casaluci et al, 2024); and other advanced modeling methods such as Bayesian physiologically based pharmacokinetic models, population-based ADME simulators, hidden Markov models, and population ecology and bioenergetic tools (Brooks et al, 2024;Manaia et al, 2024;Margiotta-Casaluci et al, 2024).…”

“…Alongside this, there have been major advances in the development of adverse outcome pathways (AOPs) for PPCPs from different molecular initiation events, providing us with a much stronger foundation for extrapolating molecularlevel effects to effects on whole organisms (Brooks et al, 2024;Margiotta-Casaluci et al, 2024). The experimental effects testing area has seen the development of a range of new approach methodologies aimed at reducing the use of wholeanimal tests, including approaches for bioaccumulation, weight-of-evidence approaches, and omics-based applications (Langan et al, 2024). The last decade has also seen an increase in the amount of data on the ecotoxicological interactions of mixtures of pharmaceuticals, including mixture effects at the molecular level; and this has helped us to evaluate mixture toxicity models for estimating the effects of pharmaceutical mixtures (Kidd et al, 2024).…”

Establishing a NexGen, mechanism‐based environmental risk assessment paradigm shift: Are we ready yet?

“…The goal is within reach, but requires a global, multidisciplinary, and inclusive approach to establish consensus. A concerted effort and orchestration between ALL relevant stakeholders (academia, industry, civil society, regulators, and decision makers) (Langan et al, 2023) remains the foundation for seamless science translation into fit-for-purpose tools for enhanced human and environmental protection.…”

“…The goal is within reach, but requires a global, multidisciplinary, and inclusive approach to establish consensus. A concerted effort and orchestration between ALL relevant stakeholders (academia, industry, civil society, regulators, and decision makers) (Langan et al, 2023) remains the foundation for seamless science translation into fit‐for‐purpose tools for enhanced human and environmental protection.

A concerted effort and orchestration between ALL relevant stakeholders (academia, industry, civil society, regulators, and decision makers) remains the foundation for seamless science translation into fit‐for‐purpose tools for enhanced human and environmental protection.

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Cross‐Species Extrapolation of Biological Data to Guide the Environmental Safety Assessment of Pharmaceuticals—The State of the Art and Future Priorities

“…This ambition could be realized, at least partially, by developing a battery of novel scalable and, most importantly, predictive in vitro and in silico methods (e.g., artificial intelligence [AI]-powered quantitative structure-activity relationships, in vitro organoids) for the detection of species-specific toxicity in the species of interest (e.g., fish; reviewed by Langan et al, 2024). However, even in a scenario in which this novel battery of "replacement, reduction, and refinement" (3Rs)-friendly methods were to become available, the volume of ecotoxicity data generated for human pharmaceuticals will always be much smaller than the volume of mammalian data generated for the purposes of human safety and efficacy assessment.…”