Evaluating the Functional Equivalency of Test Organism Performance in Negative and Solvent Controls During Chronic Sediment Ecotoxicity Studies Based on US Environmental Protection Agency Guidance

Posted on 22 March 2023 by

Abstract

The US Environmental Protection Agency (USEPA) considers sediment toxicity tests as conditional registration requirements for pesticides with soil Kd ≥50 L/kg-solid, Koc ≥1000 L/kg-organic carbon, or log Kow ≥3. The hydrophobicity of these compounds often necessitates use of solvents to ensure accurate and homogeneous dosing of spiked-sediment studies. For sediment tests, a volatile solvent (e.g., acetone) is generally used as a transient carrier. Due to low water solubility, test material is dissolved in a volatile solvent to create stock solutions. A measured aliquot of stock solution is then mixed with sand substrate, after which the solvent is evaporated. This spiking process results in negligible solvent exposure to organisms. In 2016, USEPA released final ecotoxicity test guidelines for subchronic freshwater (850.1735) and marine (850.1740) sediment test. These methods provide an option for conducting experiments with only a solvent control and no negative control. To adopt this testing strategy, functional equivalency between the negative and solvent control must be demonstrated. These test guidelines describe specific factors that should be considered for evaluating functional equivalency, including (a) the concentration of solvent in the test sediment after evaporation, (b) the levels of solvent that are known to affect organism health, (c) the known impurities in the solvent and their potential impact on organism health, and (d) the historical organism performance of solvent versus negative controls. Our analysis considers these factors and overall supports the elimination of the negative control requirement because this change is unlikely to impact the robustness or interpretability of spiked-sediment toxicity tests. Environ Toxicol Chem 2023;00:1–7. © 2023 CropLife America. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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

Posted on 20 March 2023 by

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.

Broadening the Perspective on Reducing Pharmaceutical Residues in the Environment

Posted on 21 February 2023 by

Abstract

The present study reviews options for reducing harm from pharmaceuticals that are known to cause adverse impacts by their presence in the environment. It reviews recent global and European Union policy development, which could go further in recognizing and addressing the issue in a global context. It considers green chemistry, which can help clean up production processes but holds only long-term promise for creating “green” alternatives. It explores the potential of health promotion and disease prevention, which can contribute significantly to a reduction of the disease burden and thus the need for medicines, both for infectious and for noncommunicable disease. Eco-directed sustainable prescribing practices are reviewed, which have been adopted successfully to reduce the use of harmful pharmaceuticals. We note recent developments in medicines optimization and precision medicine, which hold promise for improving patient outcomes, saving costs, and reducing pharmaceutical use, through individually tailored prescribing whereby the patient codecides their therapy. Waste prevention through reuse or redistribution is beginning to find public support and “take-back” waste disposal schemes set up via extended producer responsibility systems have achieved high returns. Finally, the paper summarizes preferred advanced wastewater technologies, including innovative low-cost, low-energy options. In summary, although end-of-pipe options have a role to play, particularly for highly concentrated wastewaters, solutions further up the medicinal chain and disease prevention interventions, informed by a broad view of health and health care, are needed to pursue a much greater potential reduction of pharmaceuticals in the environment than can be achieved by end-of-pipe solutions alone. Environ Toxicol Chem 2023;00:1–11. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

The Complex Interplay Between Antibiotic Resistance and Pharmaceutical and Personal Care Products in the Environment

Posted on 8 February 2023 by

Abstract

Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are important environmental contaminants. Nonetheless, what drives the evolution, spread, and transmission of antibiotic resistance dissemination is still poorly understood. The abundance of ARB and ARGs is often elevated in human-impacted areas, especially in environments receiving fecal wastes, or in the presence of complex mixtures of chemical contaminants, such as pharmaceuticals and personal care products. Self-replication, mutation, horizontal gene transfer, and adaptation to different environmental conditions contribute to the persistence and proliferation of ARB in habitats under strong anthropogenic influence. Our review discusses the interplay between chemical contaminants and ARB and their respective genes, specifically in reference to co-occurrence, potential biostimulation, and selective pressure effects, and gives an overview of mitigation by existing man-made and natural barriers. Evidence and strategies to improve the assessment of human health risks due to environmental antibiotic resistance are also discussed. Environ Toxicol Chem 2023;00:1–16. © 2022 SETAC

Withdrawn: Mercury Concentrations in Lake Sturgeon from Six River Systems in Manitoba, Canada

Posted on 30 January 2023 by nWolfgang Jansenn

Abstract

The above article from Environmental Toxicology and Chemistry, published online on December 21, 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/abs/10.1002/etc.5548), has been withdrawn by agreement between the author, the Society of Environmental Toxicology and Chemistry, and Wiley Periodicals LLC. The article has been withdrawn because it contains copyright protected work that the copyright holder did not agree to have published.

Do Pharmaceuticals in the Environment Pose a Risk to Wildlife?

Posted on 23 January 2023 by

Abstract

The vast majority of knowledge related to the question “To what extent do pharmaceuticals in the environment pose a risk to wildlife?” stems from the Asian vulture crisis (>99% decline of some species of Old World vultures on the Indian subcontinent related to the veterinary use of the nonsteroidal anti-inflammatory drug [NSAID] diclofenac). The hazard of diclofenac and other NSAIDs (carprofen, flunixin, ketoprofen, nimesulide, phenylbutazone) to vultures and other avian species has since been demonstrated; indeed, only meloxicam and tolfenamic acid have been found to be vulture-safe. Since diclofenac was approved for veterinary use in Spain and Italy in 2013 (home to ~95% of vultures in Europe), the risk of NSAIDs to vultures in these countries has become one of the principal concerns related to pharmaceuticals and wildlife. Many of the other bodies of work on pharmaceutical exposure, hazard and risk to wildlife also relate to adverse effects in birds (e.g., poisoning of scavenging birds in North America and Europe from animal carcasses containing pentobarbital, secondary and even tertiary poisoning of birds exposed to pesticides used in veterinary medicine as cattle dips, migratory birds as a vector for the transfer of antimicrobial and antifungal resistance). Although there is some research related to endocrine disruption in reptiles and potential exposure of aerial insectivores, there remain numerous knowledge gaps for risk posed by pharmaceuticals to amphibians, reptiles, and mammals. Developing noninvasive sampling techniques and new approach methodologies (e.g., genomic, in vitro, in silico, in ovo) is important if we are to bridge the current knowledge gaps without extensive vertebrate testing. Environ Toxicol Chem 2023;00:1–16. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Regulatory Risk Assessment of Pharmaceuticals in the Environment: Current Practice and Future Priorities

Posted on 16 January 2023 by nRik Oldenkamp, nTimo Hamers, nJohn Wilkinson, nJaap Slootweg, nLeo Posthuman

Abstract

How can data on the occurrence of pharmaceuticals and personal care products (PPCPs) in the environment and the quality of ecosystems exposed to PPCPs be used to determine whether current regulatory risk assessment schemes are effective? This is one of 20 “big questions” concerning PPCPs in the environment posed in a landmark review paper in 2012. Ten years later, we review the developments around this question, focusing on the first P in PPCPs, that is, pharmaceuticals, or more specifically the active ingredients included in them (active pharmaceutical ingredients, APIs). We illustrate how extensive data on both the occurrence of APIs and the ecotoxicological sensitivity of aquatic species to them can be used in a retrospective risk assessment. In the Netherlands, current regulatory risk assessment schemes offer insufficient protection against direct ecotoxicological effects from APIs: the toxic pressure exerted by the 39 APIs included in our study exceeds the policy-related protective threshold of 0.05 (the “95%-protection level”) in at least 13% of sampled surface waters. In general, anti-inflammatory and antirheumatic products (e.g., diclofenac, ibuprofen) contributed most to the overall toxic pressure, followed by sex hormones and modulators of the genital system (e.g., ethinylestradiol) and psychoanaleptics (e.g., caffeine). We formulated three open questions for future research. The first relates to improving the availability and accessibility of good-quality ecotoxicity data on pharmaceuticals for the global scientific, regulatory, and general public. The second relates to the adaptation of regulatory risk assessment frameworks for developing regions of the world. The third relates to the integration of effect-based and ecological approaches into regulatory risk assessment practice. Environ Toxicol Chem 2023;00:1–12. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

What Approaches Should be Used to Prioritize Pharmaceuticals and Personal Care Products for Research on Environmental and Human Health Exposure and Effects?

Posted on 16 December 2022 by

Abstract

Pharmaceuticals and personal care products (PPCPs) are released from multiple anthropogenic sources and thus have a ubiquitous presence in the environment. The environmental exposure and potential effects of PPCPs on biota and humans has aroused concern within the scientific community and the public. Risk assessments are commonly conducted to evaluate the likelihood of chemicals including PPCPs that pose health threats to organisms inhabiting various environmental compartments and humans. Because thousands of PPCPs are currently used, it is impractical to assess the environmental risk of all of them due to data limitations; in addition, new PPCPs are continually being produced. Prioritization approaches, based either on exposure, hazard, or risk, provide a possible means by which those PPCPs that are likely to pose the greatest risk to the environment are identified, thereby enabling more effective allocation of resources in environmental monitoring programs in specific geographical locations and ecotoxicological investigations. In the present review, the importance and current knowledge concerning PPCP occurrence and risk are discussed and priorities for future research are proposed, in terms of PPCP exposure (e.g., optimization of exposure modeling in freshwater ecosystems and more monitoring of PPCPs in the marine environment) or hazard (e.g., differential risk of PPCPs to lower vs. higher trophic level species and risks to human health). Recommended research questions for the next 10 years are also provided, which can be answered by future studies on prioritization of PPCPs. Environ Toxicol Chem 2022;00:1–14. © 2022 SETAC

Does Environmental Exposure to Pharmaceutical and Personal Care Product Residues Result in the Selection of Antimicrobial‐Resistant Microorganisms, and is this Important in Terms of Human Health Outcomes?

Posted on 23 November 2022 by

Abstract

The environment plays a critical role in the development, dissemination, and transmission of antimicrobial resistance (AMR). Pharmaceuticals and personal care products (PPCPs) enter the environment through direct application to the environment and through anthropogenic pollution. Although there is a growing body of evidence defining minimal selective concentrations (MSCs) of antibiotics and the role antibiotics play in horizontal gene transfer (HGT), there is limited evidence on the role of non-antibiotic PPCPs. Existing data show associations with the development of resistance or effects on bacterial growth rather than calculating selective endpoints. Research has focused on laboratory-based systems rather than in situ experiments, although PPCP concentrations found throughout wastewater, natural water, and soil environments are often within the range of laboratory-derived MSCs and at concentrations shown to promote HGT. Increased selection and HGT of AMR by PPCPs will result in an increase in total AMR abundance in the environment, increasing the risk of exposure and potential transmission of environmental AMR to humans. There is some evidence to suggest that humans can acquire resistance from environmental settings, with water environments being the most frequently studied. However, because this is currently limited, we recommend that more evidence be gathered to understand the risk the environment plays in regard to human health. In addition, we recommend that future research efforts focus on MSC-based experiments for non-antibiotic PPCPS, particularly in situ, and investigate the effect of PPCP mixtures on AMR. Environ Toxicol Chem 2022;00:1–14. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Free Versus Bound Concentration: Passive Dosing from Polymer Meshes Elucidates Drivers of Toxicity in Aquatic Tests with Benthic Invertebrates

Posted on 11 October 2022 by nFabian C. Fischer, nKyoshiro Hiki, nSatoshi Endon

Abstract

Aquatic toxicity tests with benthic organisms are used to predict the toxicity of hydrophobic organic chemicals (HOCs) in sediments, assuming that the freely dissolved concentration (C _free) is a good surrogate of bioavailability in the exposure system. However, C _free of HOCs is difficult to control in water-only setups. Moreover, the role of dissolved organic carbon (DOC) in the occurrence of toxicity needs clarification because DOC concentrations in sediment porewater can be substantially higher than in typical test water. We introduced biocompatible polyethylene meshes with high sorptive capacities and fast release kinetics as a novel passive dosing phase, which maintained C _free and C _water (i.e., free + DOC-bound) in Hyalella azteca water-only tests. Adding the supernatant fraction of peat to test water as a DOC source increased C _water to an extent comparable to sediment porewater and significantly increased and decreased the observed toxicity of permethrin and benzo[a]pyrene, respectively, to H. azteca. This result indicates that DOC can both benefit and harm test species likely due to the increased health after ingestion of DOC and to the uptake of DOC-bound HOCs, respectively. Passive dosing in combination with the addition of sediment DOC surrogates may better reflect exposure and habitat conditions in sediment porewater than conventional aquatic tests. Environ Toxicol Chem 2022;00:1–10. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.