Linking Mechanistic Effects of Pharmaceuticals and Personal Care Products to Ecologically Relevant Outcomes: A Decade of Progress

Abstract

There are insufficient toxicity data to assess the ecological risks of many pharmaceuticals and personal care products (PPCPs). While data limitations are not uncommon for contaminants of environmental concern, PPCPs are somewhat unique in that an a priori understanding of their biological activities in conjunction with measurements of molecular, biochemical, or histological responses could provide a foundation for understanding mode(s) of action and predicting potential adverse apical effects. Over the past decade significant progress has been made in the development of new approach methodologies (NAMs) to efficiently quantify these types of endpoints using computational models and pathway‐based in vitro and in vivo assays. The availability of open‐access knowledgebases to curate biological response (including NAM) data and sophisticated bioinformatics tools to help interpret the information also has significantly increased. Finally, advances in the development and implementation of the adverse outcome pathway framework provide the critical conceptual underpinnings needed to translate NAM data into predictions of the ecologically relevant outcomes required by risk assessors and managers. The evolution and convergence of these various data streams, tools, and concepts provides the basis for a fundamental change in how ecological risks of PPCPs can be pragmatically assessed. Environ Toxicol Chem 2022;00:1–12. © 2022 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

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).…”

“…effects following short-term exposures of single species to considering effects of chronic exposure on food webs (Kidd et al, 2024). It is impossible to study everything, so to deliver all of this will require a more systematic approach to generate the necessary in vitro and in vivo data to support these analyses (Ankley et al, 2024;Kidd et al, 2024). Improved access to data for a range of stakeholders would help facilitate a better understanding of the environmental risks of PPCPs (Oldenkamp et al, 2024).…”

“…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).…”

“…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).…”

Environmental Risks of Pharmaceutical Mixtures in Aquatic Ecosystems: Reflections on a Decade of Research

“…Another advantage of RNA-Seq is that it allows for the design of ecologically relevant experiments, such as those investigating the toxicity of APIs in the context of additional stressors like climate change (Almeida et al, 2018) or with transplanted organisms to assess their plasticity when exposed to different pollution sources (Rivetti et al, 2015). By using these experimental approaches, alongside DNA-and RNAbased methods, we can bridge the knowledge gap regarding the real-world impacts of API mixtures and gain insights into the linkages between molecular initiating events and adverse outcomes, which can range from cellular to population-level effects in nontarget organisms (Ankley et al, 2010(Ankley et al, , 2024Späth et al, 2022).…”