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

Environmental Toxicology and Chemistry, Год журнала: 2024, Номер 43(3), С. 481 - 487

Опубликована: Фев. 8, 2024

Pharmaceuticals and personal care products (PPCPs) include numerous chemical classes to prevent or treat human animal disease improve the quality of daily life humans. During cycles these products, it is inevitable that they will be released natural environment. It is, therefore, not surprising a wide range ingredients used in PPCPs has been detected widely surface waters, soils, sediments, groundwaters across world (Aus der Beek et al., 2016; Wilkinson 2022). many are biologically active compounds designed interact with specific pathways processes targets humans animals. Concerns have therefore raised about potential effects environment on public health, biodiversity, ecosystem services. Since late 1990s, substantial amount work done determine occurrence, fate, effects, risks Recognizing concerns around value providing some focus for research area, 2011 Pharmaceutical Advisory Group Society Environmental Toxicology Chemistry (SETAC) initiated horizon scanning exercise identify top questions related pharmaceuticals The hope then was results would help informing design, coordination, implementation future environmental programs thus provide better understanding relative substances environment, allowing us more effectively control manage risks. employed "key question" approach where were Initially solicited from academic, government, business communities world. A list 101 discussed at an international expert workshop, top-20 developed, falling into seven categories: (1) prioritization assessment, (2) exposure, (3) bioavailability uptake, (4) characterization, (5) risk risk, (6) antibiotic resistance, (7) management. Following workshop ranked by importance. In 2012, this published review paper Health Perspectives entitled "Pharmaceuticals Personal Care Products Environment: What Are Big Questions" (Boxall 2012). publication, had significant impact community, being cited over 1000 times. also provided foundation broader SETAC Global Horizon Scanning Exercise, which identified priority sustainable North America, Asia, Australasia, Europe, Latin America. series papers covering each geographical regions (Gaw 2019; Fairbrother Furley 2018; Leung 2020; van den Brink 2018). As 2022 10th anniversary we felt timely state science PPCP 20 look forward next 10 years. This special issue developed leading researchers invited give their perspectives current level knowledge different 2012 new topic area decade. developing manuscripts, authors asked consider question multiple perspectives—scientific, regulatory, technical—and go well beyond own work. We authoritative up-to-date subject matter relating question. issue, provides overview 14 key (Table 1) forward-looking synthesis priorities coming Aquatic How Can Regions Risk Be Identified Future? Taken together, show progress made since our inputs, advancing approaches characterize terms prioritization, exposure-, hazard-, risk-based applied most concern (Mo 2024). These now geographies, giving insight much improved uptake organisms. Progress here development models estimate ionizable invertebrates, fish, earthworms, plants (Carter developments supported vitro testing methodologies increasing access machine learning modeling methodologies, such as artificial neural networks Significant methods extrapolate For pharmaceuticals, moved evaluation single-drug organisms conservation all know drug species (Margiotta-Casaluci Alongside this, there major advances adverse outcome (AOPs) molecular initiation events, stronger extrapolating molecular-level whole (Brooks 2024; Margiotta-Casaluci experimental seen aimed reducing use whole-animal tests, including bioaccumulation, weight-of-evidence approaches, omics-based applications (Langan last decade increase data ecotoxicological interactions mixtures mixture level; helped evaluate toxicity estimating pharmaceutical (Kidd effects-directed analyses, high-resolution mass spectrometry nontargeted analysis, means placed drivers complex undefined Increasing availability openly available software systems, ECODrug, SeqAPASS, MAPPFAST, AOPwiki, sources ecotoxicity (e.g., REACH dossiers, ToxCast), community understand aquatic terrestrial (Ankley 2024) advance precision assessments past decade, number monitored risen, occurrence globe (Wilkinson improvement, exposure ePiE, PhATE, STREAM-EU, GLOBAL-FATE, predictions finer scales than before allowed assessed broadly identification wildlife, select classes, nonsteroidal inflammatory drugs, euthanasia veterinary parasiticides, estrogens, avian (Bean still questionable, however, whether really yet real impacts (Sumpter example, prospective risk-assessment systems indicated true might underestimated using regulatory (Oldenkamp links between antimicrobial resistance (AMR) health resulted wealth chemicals, particularly antibiotics, selection. mechanisms selection AMR (Manaia volume laboratory-derived minimal selective concentrations, concentrations shown promote horizontal gene transfer, derive predicted-no-effect (PNECs) Stanton evidence contributing crisis stronger, comparisons monitoring PNECs indicating regions, associations found acquisition demonstrated settings (Stanton risks, risk-management landscape very 2012. higher up policy agenda, pollution recognized organizations United Nations Environment Programme World Organization. European Union recently adopted strategic (Helwig Work management begun cycle problem one perspective wider strategies considered/explored, promotion reduce use, green chemistry design less harmful produce medicines lower profiles, changes prescription practices, waste wastewater treatment Despite how them, gaps knowledge; highlight areas needed. Many stress need broadening 2024), chemicals Carter stages On side, levels organization become quantitative, taxonomic domains applicability 2024); needs functional endpoints prevention protection biodiversity services move away considering following short-term exposures single chronic food webs impossible study everything, so deliver require systematic generate necessary vivo support analyses Kidd Improved stakeholders facilitate More needed underrepresented geographies likely vulnerable Exposure efforts toward working temporal resolutions factors pH modify effects-based batteries methods) in-field ecological continue role plays widen non-antibiotic contaminants start While strides PPCPs, solutions implemented rapidly equitably Human integrated process, could highly beneficial benefit "new" introduced issue. citizen monitor non-invasive tools minimize animals Bean Langan genetic modification methods, clustered, regularly interspaced short palindromic repeats, coupled imaging omics Manaia high-throughput methods—for absorption, distribution, metabolism, excretion tests (ADME; other advanced Bayesian physiologically based pharmacokinetic models, population-based ADME simulators, hidden Markov population ecology bioenergetic big Boxall al. (2012) fodder wave articles subsequent palpable, anthropogenic toxins matrices. considerably because above, Sumpter (2024) point out unable answer important 2012: nonchemical stressors biological environment? despite fact 18,000 documents depressing if, 2032, similar situation. Moving forward, take hypothesis-driven address preventing answering 2) direction endeavor sustainability healthcare products. do prioritize limited usage data? addition apical endpoints, can responses utilized prioritization? microbial Which types considered during approaches? partitioning sorption behaviors strongly ionizing among species? does membrane permeability ions influence bioaccumulation PPCPs? To what extent salts associated complexes influencing bioaccumulation? biotransformation elimination vary within currently focused profiles? uncertainty modeling? map targets? best way extract comparative biology make usable toxicology applications? quantitative relationship subapical overcome (and resource) limitations model laboratory organisms? develop scalable battery characterization pharmacokinetics, pharmacodynamics fish quantity, taxonomic/species coverage, quality, annotation sequences expand information studies bioinformatics conserved reflected ecotoxicology testing? advantage combined target sequence similarity protein structural inform extrapolation safety assessments? evolutionary sensitivity? co-occur locations above effect thresholds anticipated cross-species eco-exposomics accelerate its practice engineering? criteria drive adoption alternative decision-making regarding extrapolation? implement collect bioactivity greater diversity taxa? AOPs (including qAOPs) relevant predicting expanded? additional knowledgebases computational efficiently conduct hazard/risk API populations exposed—focusing patterns coexposure global dynamics? sensitive type mixture(s), both direct indirect effects? particular "omics," assess hazards mixtures? cause synergistic/interactive toxicities APIs under environmentally realistic conditions? evolve discussion mutual developers end users (industry/regulatory agencies) when further methods/approaches change emerges? divergence no-observed-effect assessed? variability taxa attributable modifiers like abiotic climate change, biotic variable incorporated? uncertainties traditional define benchmark scientific acceptance socioeconomic geophysical "risk factors" pose greatest health? via Where significant? engagement robust reliable typically studied scientists analytical capacity limited? novel techniques silico gradients accessible, accurate, "green"/sustainable? good-quality required assessment easily findable, interoperable, reusable scientific, general public? frameworks fit purpose world? effect-based practice? affecting reptiles, amphibians, mammals? antibiotics antimicrobials presence environments? MSCs nonantibiotic situ align MSCs? transfer Does transmission various underresearched environments result outcome? planetary context? synergies improving value-based care, acknowledging societal complexities issues? put place, contexts, aid integration transformative achievable through cleaner declare no conflict interest. Alistair B. A. Boxall, Bryan W. Brooks: Conceptualization; Writing—original draft; Writing—review & editing. There article, introduction journal.

Язык: Английский

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Use of Alternatives to Animal Testing for Environmental Safety Assessment (ESA): Report from the 2023 EPAA Partners’ Forum

Regulatory Toxicology and Pharmacology, Год журнала: 2025, Номер 156, С. 105774 - 105774

Опубликована: Янв. 22, 2025

Environmental Safety Assessments (ESA) are mandatory for several regulatory purposes and an important component of stewardship/sustainability initiatives. Fish testing is used assessing chemical toxicity bioaccumulation potential; amphibians included in some jurisdictions their use increasing to assess endocrine disruption. Alternative methods becoming more available, covering the principles 3Rs (i.e., replacing, reducing refining animal tests), but incorporation still limited. A cross-sector review by European Partnership Approaches Animal Testing (EPAA), discussed status priorities accelerating adoption non-animal approaches ESA. The lack internationally agreed definition "animal testing" was recognized as a challenge. For example, with vertebrate embryos up specific developmental stages suitable refinement alternative only jurisdictions. Invertebrate offers alternatives develop tiered using last resort. Aquatic ESA identified common need all sectors areas, while terrestrial particularly relevant agrochemicals. standardization validation OECD test guidelines (TGs) fish acute have not yet triggered expected replacement settings. Priority actions these areas needed generate confidence available TGs designed alternatives, including identification applicability domains guidance/decision-trees integrating different lines evidence. Case studies under Integrated Assessment (IATA) program could facilitate further global uptake. Replacement chronic complex less advanced. dual approach suggested, short-term, exploring evidence that, alone or combination, identify when needed. second phase should focus on application those cases where information Another area interest It represents challenge also opportunity implementing mechanistic methods, addition integrate human This requires step-by-step continuous dialogue ensure that technical developments will address needs. long-term aspiration new paradigm, mapping protection goals providing connectivity between legislation environmental policies.

Язык: Английский

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

Environmental Toxicology and Chemistry, Год журнала: 2023, Номер 43(3), С. 549 - 558

Опубликована: Авг. 2, 2023

Abstract Pharmaceuticals and personal care products (PPCPs) occur as variable mixtures in surface waters receiving discharges of human animal wastes. A key question identified a decade ago is how to assess the effects long‐term exposures these PPCP on nontarget organisms. We review recent progress made assessing aquatic ecotoxicity mixtures—with focus active pharmaceutical ingredients—and challenges research needs that remain. New knowledge has arisen from use whole‐mixture testing combined with component‐based approaches, studies show often result responses meet concentration addition model. However, such have mainly been done individual species over shorter time periods, longer‐term, multispecies assessments remain limited. The targeted nontargeted gene analyses improved our understanding diverse pathways are impacted, there promising new “read‐across” methods mammalian data predict toxicity wildlife. Risk challenging given paucity ecotoxicological exposure mixtures. As such, assessment environments should priority potential for additive—as well nontarget—effects In addition, we need improve which species, life stages, relevant endpoints most sensitive types expand environmental levels regions globe poorly studied date. recommend an increased approach methodologies, particular “omics,” advance molecular mechanics mixture effects. Finally, call systematic role development antimicrobial resistance. Environ Toxicol Chem 2024;43:549–558. © 2023 SETAC.

Язык: Английский

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The use of fish cell lines as in-vitro ecotoxicological tools: A cellular solution to aquaculture sustainability

Aquaculture, Год журнала: 2024, Номер 593, С. 741302 - 741302

Опубликована: Июнь 28, 2024

Aquaculture plays a crucial role in meeting the growing demand for seafood worldwide. However, sustainability of aquaculture practices faces challenges from environmental pollutants and toxins. Traditional methods assessing aquatic toxicity often rely on whole organism tests, which can be time-consuming, expensive, ethically challenging. In recent years, utilization fish cell lines as in-vitro testing models toxicology has emerged promising alternative approach. Fish offer several advantages, including cost-effectiveness, scalability, reduced ethical concerns. This review paper provides an overview implementation toxicology, focusing their applications contaminants, mechanistic studies, biomarker discovery. Furthermore, we discuss advantages limitations compared to traditional tests explore future perspectives integrating into regulatory frameworks. Overall, integration holds great promise enhancing safety face increasing pressures.

Язык: Английский

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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

Environmental Toxicology and Chemistry, Год журнала: 2023, Номер 43(3), С. 513 - 525

Опубликована: Апрель 17, 2023

The extrapolation of biological data across species is a key aspect biomedical research and drug development. In this context, comparative biology considerations are applied with the goal understanding human disease guiding development effective safe medicines. However, widespread occurrence pharmaceuticals in environment need to assess risk posed wildlife have prompted renewed interest pharmacological toxicological entire tree life. To address challenge, "read-across" approach, based on use mammalian inform toxicity predictions species, has been proposed as an way streamline environmental safety assessment pharmaceuticals. Yet, how approach been, we any closer being able accurately predict known risk? We discuss main theoretical experimental advancements achieved last 10 years field. propose that better functional conservation targets quantitative relationship between target modulation adverse effects should be considered future priorities. This pharmacodynamic focus complemented application higher-throughput computational approaches accelerate prediction internal exposure dynamics. translation (eco)toxicology into real-world applications, however, relies (limited) availability experts skill set needed navigate complexity problem; hence, also call for synergistic multistakeholder efforts support strengthen toxicology education at global level. Environ Toxicol Chem 2024;43:513-525. © 2023 Authors. Environmental Toxicology Chemistry published by Wiley Periodicals LLC behalf SETAC.

Язык: Английский

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

Environmental Toxicology and Chemistry, Год журнала: 2023, Номер 43(3), С. 526 - 536

Опубликована: Окт. 3, 2023

Translation of environmental science to the practice aims protect biodiversity and ecosystem services, our future ability do so relies on development a precision ecotoxicology approach wherein we leverage genetics informatics species better understand manage risks global pollution. A little over decade ago, workshop focusing pharmaceuticals personal care products (PPCPs) in environment identified priority research question, "What can be learned about evolutionary conservation PPCP targets across life stages context potential adverse outcomes effects?" We review activities this area past decade, consider prospects more recent developments, identify needs develop next-generation approaches for PPCPs other chemicals waste challenges. Environ Toxicol Chem 2024;43:526-536. © 2023 SETAC. This article has been contributed by U.S. Government employees their work is public domain USA.

Язык: Английский

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Cytotoxicity of pharmaceuticals and their mixtures toward scaffold-free 3D spheroid cultures of rainbow trout (Oncorhynchus mykiss) hepatocytes

European Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 199, С. 106817 - 106817

Опубликована: Май 24, 2024

Pharmaceutical residues are widely detected in surface waters all around the world, causing a range of adverse effects on environmental species, such as fish. Besides population level (mortality, reproduction), pharmaceutical can bioaccumulate fish tissues resulting organ-specific toxicities. In this study, we developed vitro 3D culture models for rainbow trout (Oncorhynchus mykiss) liver cell line (RTH-149) and cryopreserved, primary hepatocytes (RTHEP), compared their spheroid formation susceptibility to toxic impacts pharmaceuticals. The rapidly proliferating, immortalized RTH-149 cells were shown form compact spheroids with uniform morphology just three days, thus enabling higher throughput toxicity screening that required acclimation times about one week. addition, screened cytotoxicity total fourteen clinically used human pharmaceuticals toward cultures both (metabolically inactive) RTHEP active), evaluate pharmaceuticals' own metabolism hepatotoxicity vitro. Among test substances, azole antifungals (clotrimazole ketoconazole) identified most cytotoxic, hepatic indicatively amplifying toxicity, followed by fluoxetine, levomepromazine, sertraline, which slightly less metabolically active than spheroids. individual pharmaceuticals, challenged mixtures eight if combined mixture toxicities be predicted based substances' half-maximal effect (EC50) concentrations. As result, classical concentration addition approach was concluded sufficiently accurate preliminarily informing approximate concentrations cellular level. However, direct read-across from data proven challenging inexplicit prediction

Язык: Английский

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Experimental Reporting of Fish Transcriptomic Responses in Environmental Toxicology and Ecotoxicology

Environmental Toxicology and Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Due to its increasing affordability and efforts understand transcriptional responses of organisms biotic abiotic stimuli, transcriptomics has become an important tool with significant impact on toxicological investigations hazard risk assessments, especially during development application new approach methodologies (NAMs). Data generated using transcriptomic have directly informed adverse outcome pathway frameworks, chemical biological read across, aided in the identification points departure. Using data reporting frameworks for offers improved transparency reproducibility research opportunity identify barriers adoption these NAMs, environmental toxicology ecotoxicology aquatic models. Improved also allows reexamination existing data, limiting needs experiment replication further reducing animal experimentation. Here, we use a standardized form omics-based studies, Organisation Economic Co-operation Development omics framework, which specifically reports list parameters that should be included studies used regulatory context. We focused fish RNA- Sequencing (Seq)/microarray technologies within Inconsistencies among experimental designs (toxicology vs. molecular characterization) were observed addition foundational differences sample concentration or preparation quality can affect confidence results, contribute substantially understanding mechanisms toxicants toxins. Our findings present reporting. provide several recommendations as logical steps reduce ecotoxicology.

Язык: Английский

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Transcriptomics Points-of-Departure (tPODs) to Support Hazard Assessment of Benzo[a]pyrene in Early-Life-Stage Rainbow Trout

Environmental Science & Technology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

New approach methods (NAMs) are urgently needed to address the significant ethical and economic concerns associated with live animal testing as well low throughput current toxicity frameworks. NAMs such rapid mechanistic early-life-stage fish assays promising alternatives hazard assessment approaches, they can be used derive thresholds guide decision-makers on identifying or prioritizing chemicals of concern. This study aimed benchmark concentrations from RNaseq data (transcriptomic points-of-departure; tPOD) a short-term exposure early life stages rainbow trout (RBT; Oncorhynchus mykiss) using benzo[a]pyrene (B[a]P) model compound. tPODs were then calibrated higher organizational-level responses observed during an extended 28 day period. RBT exposed 1 days post-hatch (dph) 0.079, 0.35, 1.5, 7.4, 29 μg/L (28 d time weighted average measured) B[a]P, 0.05% dimethyl sulfoxide water only controls. Benchmark concentration analysis transcriptomic at 4 dph, based most sensitive features, yielded between 0.028 0.47 B[a]P. At Cyp1a1 exhibited significantly increased catalytic activity, biochemical POD, bPODEROD,28dph 0.599 while morphometric showed growth inhibition in terms length, apical aPODlength,28dph 1.77 notable decreasing trend body weight. A pathway constructed genes end points exhibiting concentration-dependent provided further evidence supporting utility assay support chemical risk prioritization.

Язык: Английский

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Unlocking the future of Environmental Safety: a Framework for Integrating New Approach Methodologies in Decision-Making

NAM journal., Год журнала: 2025, Номер unknown, С. 100028 - 100028

Опубликована: Май 1, 2025

Язык: Английский

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