Towards Precision Ecotoxicology: Leveraging Evolutionary Conservation of Pharmaceutical and Personal Care Product Targets to Understand Adverse Outcomes Across Species and Life Stages

Abstract

Environmental science aims to protect biodiversity and ecosystem services, and our future ability to do that relies on a developing a precision ecotoxicology approach where we leverage the genetics and informatics of species to better understand and manage the risks of global pollution. A little over a decade ago, a workshop focusing on the risks of pharmaceuticals and personal care products (PPCPs) in the environment identified a priority research question, “What can be learned about the evolutionary conservation of PPCP targets across species and life stages in the context of potential adverse outcomes and effects?” Here we review the activities in this area over the past decade, consider prospects of more recent developments, and identify future research needs to develop next generation approaches for PPCPs and other global chemicals and waste challenges.

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

“…Despite the many advances in our understanding of the impacts of PPCPs on the natural environment and how to manage them, there are still significant gaps in our knowledge; and all of the special issue papers highlight areas where more work is needed. Many of the papers stress the need for broadening the research to include a much wider range of geographical areas (Oldenkamp et al, 2024;Wilkinson et al, 2024), chemicals and chemical classes (Ankley et al, 2024;Carter et al, 2024), and species and life stages (Brooks et al, 2024).…”

“…On the effects side, approaches for extrapolating from molecular-level interactions to higher levels of organization need to become more quantitative, including broader taxonomic domains of applicability (Brooks et al, 2024); and more focus needs to be placed on the functional endpoints that really matter for pollution prevention and the protection of biodiversity and ecosystem services (Brooks et al, 2024;Margiotta-Casaluci et al, 2024). Work on mixtures needs to move away from considering…”

“…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).…”

“…For pharmaceuticals, we have now moved from the evaluation of single-drug targets in organisms to an understanding of the conservation of all know drug targets in a wide range of species (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).…”

“…Significant developments in methodologies for effects-directed analyses, including increasing access to high-resolution mass spectrometry for nontargeted analysis, means that we are now much better placed to identify drivers of toxicity in complex and undefined mixtures (Kidd et al, 2024). Increasing availability of openly available software systems, such as ECODrug, SeqAPASS, MAPPFAST, AOPwiki, and sources of toxicity ecotoxicity data (e.g., REACH dossiers, ToxCast), means that the research community is much better placed to understand the effects of PPCPs on aquatic and terrestrial organisms (Ankley et al, 2024;Margiotta-Casaluci et al, 2024) and to advance the precision of environmental assessments (Brooks et al, 2024).…”