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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How the Xenopus eleutheroembryonic thyroid assay compares to the amphibian metamorphosis assay for detecting thyroid active chemicals

Regulatory Toxicology and Pharmacology, Год журнала: 2024, Номер 149, С. 105619 - 105619

Опубликована: Апрель 13, 2024

The Xenopus Eleutheroembryonic Thyroid Assay (XETA) was recently published as an OECD Test Guideline for detecting chemicals acting on the thyroid axis. However, validation did not cover all mechanisms that can potentially be detected by XETA. This study therefore initiated to investigate and consolidate applicability domain of XETA regarding following mechanisms: hormone receptor (THR) agonism, sodium-iodide symporter (NIS) inhibition, thyroperoxidase (TPO) deiodinase (DIO) glucocorticoid (GR) uridine 5'-diphospho-glucuronosyltransferase (UDPGT) induction. In total, 22 identified thyroid-active or -inactive in Amphibian Metamorphosis Assays (AMAs) were tested using Guideline. comparison showed both assays are highly concordant identifying with action related THR DIO GR agonism. They also consistently UDPGT inducers inactive. NIS investigated sodium perchlorate, TPO inhibition requires further mechanistic investigations reference resulted opposing response directions AMA. contributes refining XETA, thereby helping clarify conditions where it used ethical alternative

Язык: Английский

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Electrochemical degradation of diclofenac generates unexpected thyroidogenic transformation products: Implications for environmental risk assessment

Journal of Hazardous Materials, Год журнала: 2024, Номер 472, С. 134458 - 134458

Опубликована: Апрель 29, 2024

Язык: Английский

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

Environmental Toxicology and Chemistry, Год журнала: 2023, Номер 43(3), С. 559 - 574

Опубликована: Фев. 1, 2023

In 2012, 20 key questions related to hazard and exposure assessment environmental health risks of pharmaceuticals personal care products in the natural environment were identified. A decade later, this article examines current level knowledge around one lowest-ranking at that time, number 19: "Can nonanimal testing methods be developed will provide equivalent or better data compared with vivo methods?" The inclusion alternative replace, reduce, refine animal within regulatory context risk chemicals generally faces many hurdles, although varies both by organism (human-centric vs. other), sector, geographical region country. Focusing on past 10 years, only works might reasonably considered contribute advancements field aquatic are highlighted. Particular attention is paid contemporary interest importance, representing progress (1) development which such as bioaccumulation, (2) weight evidence, (3) -omic-based applications. Evolution convergence these areas offer basis for fundamental frameshifts how collated used protection taxa across breadth environment. Looking future, we a tipping point, need global inclusive approach establish consensus. Bringing together (both new old) decision-making require concerted effort orchestration. Environ Toxicol Chem 2024;43:559-574. © 2023 Authors. Environmental Toxicology Chemistry published Wiley Periodicals LLC behalf SETAC.

Язык: Английский

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Endocrine disruption assessment in aquatic vertebrates – Identification of substance-induced thyroid-mediated effect patterns

Environment International, Год журнала: 2024, Номер 191, С. 108918 - 108918

Опубликована: Июль 27, 2024

According to the World Health Organisation and European Commission definitions, substances shall be considered as having endocrine disrupting properties if they show adverse effects, have activity effects are a consequence of (using weight-of-evidence approach based on biological plausibility), unless not relevant humans or non-target organisms at (sub)population level. To date, there is no decision logic how establish disruption via thyroid modality in non-mammalian vertebrates. This paper describes an evidence-based compliant with integrated testing assessment (IATA) concept, identify thyroid-mediated effect patterns aquatic vertebrates using amphibians models for assessment. The includes existing test guidelines methods proposes detailed considerations select assays interpret findings. If mammalian dataset used starting point indicates concern, Xenopus Eleutheroembryonic Thyroid Assay allows ruling out vertebrates, whereas Amphibian Metamorphosis its extended, fixed termination stage variant inform both potentially population-relevant adversity. In evaluating findings, response all assay endpoints considered, including direction changes. Thyroid-mediated identified individual level amphibian tests followed by mode-of-action population relevance assessments. Finally, data overarching evaluation. has been designed generically can adapted, e.g. accommodate fish once available It also ensures that scientifically information animal minimised. proposed included regulatory assessments facilitate conclusion whether meet disruptor definition

Язык: Английский

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Control Performance Of Amphibian Metamorphosis Assays With Xenopus Laevis

Regulatory Toxicology and Pharmacology, Год журнала: 2025, Номер unknown, С. 105773 - 105773

Опубликована: Янв. 1, 2025

The amphibian metamorphosis assay (AMA) is an in vivo screen to assess potential interactions of chemicals with the thyroid system. Tadpoles are exposed for 21-days, then assessed development and growth after 7 days at test termination. This paper presents data from studies performed satisfy orders US EPA's Endocrine Disruptor Screening Program. Data Evaluation Records were used collate control variability performance biological endpoints AMAs conducted different laboratories, supplemented recent studies. We examine statistical power AMA endpoint analysis whether historical (HCD) can assist evidence-based interpretation endpoints, 52 laboratories. HCD be understand post validation. identifies some need flexibility Test Guidelines' criteria, including latitude analytical late-stage animals. Additionally, more guidance suggested feed regiments selection criteria batches animals initiate assay. Potential Guideline refinements that improve have reduce number vertebrate conduct identified discussed.

Язык: Английский

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Screening for Endocrine Bioactivity Potential of Tobacco Product Chemicals Including Flavor Chemicals

Environmental Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Adolescence and pregnancy involve elevated levels of hormones (e.g., estrogen, androgen) during which exposure to endocrine disruptors could have long-term developmental reproductive toxicity (DART) effects. Therefore, the use prevalence abuse liability electronic nicotine delivery systems (ENDS) among adolescents youth, pregnancy, raises concerns about possible disruptors. In addition, adverse effects on wildlife environmental health. While many studies focus carcinogenicity mutagenicity tobacco products, research efforts screening chemicals in products for disruption potential are few. this study, we curated 5179 smoke, 2803 flavor chemicals, 156 e-liquid from literature or openly available databases. We screened bioactivity using new approach methodologies (NAMs) developed through US Environmental Protection Agency's Endocrine Disruptor Screening Program. The specific NAMs, estrogenic androgenic pathway models, identified 137 34 three (Veratraldehyde, (2E)-3-Phenylprop-2-enal, 2'-Acetonaphthone) as "active," indicating bioactivity. Further, with potential, 48 were environmentally persistent, 29 bioaccumulative, 19 both persistent bioaccumulative. Our findings document bioactivity, human These results also underscore importance DART flavors. Overall, our study characterizes provides a list consider future ecological health risk assessments.

Язык: Английский

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Cross-species comparisons of plasma binding and considerations for data evaluation

Toxicology in Vitro, Год журнала: 2025, Номер unknown, С. 106036 - 106036

Опубликована: Фев. 1, 2025

Язык: Английский

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Cross-taxa Extrapolation: Is There a Role for Thyroid Hormone Conjugating Liver Enzymes during Amphibian Metamorphosis?

Regulatory Toxicology and Pharmacology, Год журнала: 2025, Номер unknown, С. 105810 - 105810

Опубликована: Март 1, 2025

Язык: Английский

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Challenges and Opportunities in the Development and Adoption of New Approach Methods (NAMs)

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

InfoMetricsFiguresRef. Journal of Agricultural and Food ChemistryASAPArticle This publication is Open Access under the license indicated. Learn More CiteCitationCitation abstractCitation referencesMore citation options ShareShare onFacebookXWeChatLinkedInRedditEmailBlueskyJump toExpandCollapse ViewpointMarch 19, 2025Challenges Opportunities in Development Adoption New Approach Methods (NAMs)Click to copy article linkArticle link copied!Steven L. Levine*Steven LevineBayer U.S. - Crop Science, Chesterfield, Missouri 63017, United States*[email protected]More by Steven Levinehttps://orcid.org/0000-0002-5872-2351Leah S. Riter*Leah RiterBayer Leah Riterhttps://orcid.org/0000-0001-5702-161XLaurent LagadicLaurent LagadicBayer AG R&D, Science Division, Environmental Safety, 40789 Monheim am Rhein, GermanyMore Laurent LagadicAdriana C. BejaranoAdriana BejaranoEmergency Response Office Restoration, National Oceanic Atmospheric Administration, Seattle, Washington 98115, StatesMore Adriana BejaranoNatalie BurdenNatalie BurdenNational Centre for Replacement, Refinement Reduction Animals Research, London NW1 2BF, KingdomMore Natalie BurdenLyle D. BurgoonLyle BurgoonRaptor Pharm & Tox, Ltd., Apex, North Carolina 27502, Lyle BurgoonRichard A. BeckerRichard BeckerAmerican Chemistry Council, Washington, D.C. 20002, Richard BeckerJessica P. RymanJessica RymanAmerican Jessica RymanKevin ArmbrustKevin ArmbrustDepartment College Coast Environment, Louisiana State University, Baton Rouge, 70803, Kevin Armbrusthttps://orcid.org/0000-0001-5894-3675Open PDFJournal ChemistryCite this: J. Agric. Chem. 2025, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acs.jafc.5c02930https://doi.org/10.1021/acs.jafc.5c02930Published March 2025 Publication History Received 6 2025Published online 19 2025article-commentary© The Authors. Published American Chemical Society. licensed CC-BY-NC-ND 4.0 . License Summary*You are free share (copy redistribute) this any medium or format within parameters below:Creative Commons (CC): a Creative license.Attribution (BY): Credit must be given creator.Non-Commercial (NC): Only non-commercial uses work permitted. No Derivatives (ND): Derivative works may created purposes, but sharing prohibited. View full license*DisclaimerThis summary highlights only some key features terms actual license. It not has no legal value. Carefully review before using these materials. underCC-BY-NC-ND share(copy below: Attribution *DisclaimerThis creator. Non-Commercial ACS Publications© SocietySubjectswhat subjects Article automatically applied from Subject Taxonomy describe scientific concepts themes article. Assays Elements Nicotinamide Safety Testing assessment At 2024 Agrochemicals (AGRO) Division Society's fall meeting, virtual in-person symposia brought together international experts provide viewpoints on challenges opportunities increase adoption new approach methodologies (NAMs) regulatory frameworks. NAMs generally defined as technology, methodology, that provides information about chemical hazard risk replaces, reduces, refines animal testing. Key drivers transition reduce testing, characterize mechanisms toxicity, prioritize where further testing needed inform assessment. diverse can include silico methods such quantitative structure–activity relationships (QSARs), omics, read-across, vitro assays, organoids, transgenic eleutheroembryonic assays. Despite their rapid development, frameworks been relatively slow. slow due one more factors adapting relevant legislation, lengthy validation process, limitations context use, building confidence, adopting harmonized test guidelines. Viewpoint presented speakers accelerate development NAMs, build achieve societal acceptance, toward greater (Table 1).Table 1. Challenges Accelerate Their Transition Regulatory AdoptionScientific Confidence Frameworks (SCFs) Validation: Validating crucial ensure reliability relevance. As an alternative traditional SCFs robust flexible modernize do preclude ability conduct ring trials when deemed necessary. Whether relevance demonstrated SCF validation, following approaches necessary NAM confidently used decision-making without compromising human environmental safety. Case Studies: studies critical demonstrate effectiveness, address uncertainty, improve NAMs. concrete examples how successfully specific context, which helps confidence understanding among users ultimately encourages wider adoption. Acceptance: Advocating frameworks, innovation while ensuring safety, will support acceptance Cooperative research community, industry, agencies establishing guidelines standards increased implementation safety evaluations. A lack clear guidance create hesitation researchers manufacturers innovate adopt submissions. Societal Improving public trust achieved through combination factors. Some highlighting benefits, education demystify them public, transparent communication managers with reassurances protection humans environment comprised, engagement stakeholders early publishing results reputable peer-reviewed journals, presenting findings at conferences. Interdisciplinary Multipartite Collaboration: Building promote fostering interdisciplinary multipartite collaborative efforts, significant investments, maximizing data opportunities, continuing education, addressing knowledge gaps innovation, large sets enhance predictive models, integration into endorsed adverse outcome pathway (AOP) harmonization protocols, developing use.Outlook Research Needs Wildlife Endocrine Disruption (ED)Click section linkSection copied!NAMs being developed wildlife species For example, cross-species extrapolation useful restricted prohibited concerns regarding federally listed threatened endangered species. However, related reliability, have domains applicability, documentation strengths limitations. These elements establish extrapolation. Therefore, fit-for-purpose case studies, focused primarily evaluation involving developers, users, regulators, essential encouraged advancing incorporation standard practice extrapolation.As part ED assessments, identification endocrine activity could lead intact organism. Such valuable screening prioritization chemicals highest concern. eleutheroembryo assays nonmammalian (e.g., OECD 248, 250, 251, 252) additional development. There example assessments assay accepted purposes conditions place generating vivo assay. (1) is, however, gap based fish amphibian biology, though it whether existing biology equally informative.Short-term, needs center around refining applicability available improved ADME (absorption, distribution, metabolism, excretion) processes use curation high-quality help contextualize demonstrating bring value processes, coverage In long term, there need our linkages between NAM-derived mechanistic outcomes technologies cell painting, transcriptomics, organ-on-a-chip) tools explore pathways beyond those currently assessed requirements. (2)Role Scientific Modernize Validation NAMsClick copied!A limitation develop guidelines) they require (i.e., "round-robins") time- resource-intensive. led calls "fit-for-purpose" raised question would operationalized, well creating reproducibility crisis if formal were abandoned. (3)SCFs, recently adopted Interagency Coordinating Committee Alternative Methods, (4) scientifically validation. theory, anyone intended purpose product etc.). common biological relevance, technical characterization, analysis integrity), peer review. (4,5) across indicate consensus SCF. Importantly, extensive situations still desired. shared responsibility science community press ahead implementing evaluating achieves benchmarks each its decision context.Building Public Trust copied!The relies upon scientists reliable accurate data. Congress like see congressional quickly erode inappropriately. discussion conclusions drawn therefrom illustrate principles. (6−8) First, decisions meet rigorous comply inference models validated. Second, generate hypotheses, hypotheses rigorously tested incorporated decisions. whole core principles.Remarks Future ProspectsClick copied!Significant advancements over past several decades made areas context. potential accuracy toxicity providing environmentally reducing reliance Although progress continue adapt flexibility incorporate use.Author InformationClick copied!Corresponding AuthorsSteven Levine Bayer States; https://orcid.org/0000-0002-5872-2351; Email: [email protected]Leah Riter https://orcid.org/0000-0001-5702-161X; protected]AuthorsLaurent Lagadic GermanyAdriana Bejarano Emergency StatesNatalie Burden KingdomLyle Burgoon Raptor StatesRichard Becker StatesJessica Ryman StatesKevin Armbrust Department https://orcid.org/0000-0001-5894-3675NotesThe authors declare competing financial interest(s): S.L.L., L.S.R., L.L. employees developer manufacturer pest control products, expressed does necessarily represent view Science. R.A.B. J.P.R. employed Council (ACC, https://www.americanchemistry.com/), industry trade association represents set companies engaged business chemistry; list ACC members, https://www.americanchemistry.com/about-acc/membership. contents manuscript solely reflect views policies ACC. paper reflects co-author A.C.B. official positions NOAA Commerce. N.B. L.D.B. conflicts received funding work.ReferencesClick copied! references 8 other publications. 1Arena, M.; van der Linden, Annex Use XETA Assessment Strategy ECHA/EFSA. Guidance Identification Disruptors Context Regulations (EU) 528/2012 (EC) 1107/2009. EFSA 2018, 16 (6), 5311Google ScholarThere corresponding record reference.2Mitchell, A.; Burden, N.; Bonnell, Hecker, Hutchinson, T. H.; Jagla, LaLone, Lagadic, L.; Lynn, G.; Shore, B.; Song, Y.; Vliet, Wheeler, R.; Embry, M. R. Methodologies Activity Toolbox: Fish Amphibians. Environ. Toxicol. 2023, 42 (4), 757– 777, DOI: 10.1002/etc.5584 Google reference.3Jacobs, Hoffmann, S.; Hollnagel, H. Kern, P.; Kolle, Natsch, Landsiedel, Avoiding Reproducibility Crisis Toxicology-On Fundamental Role Ring Trials. Arch. 2024, 98, 2047– 2063, 10.1007/s00204-024-03736-z reference.4Interagency (ICCVAM). Validation, Qualification, Acceptance Methodologies; ICCVAM, Report. https://ntp.niehs.nih.gov/sites/default/files/2024-03/VWG_Report_27Feb2024_FD_508.pdf (accessed 2025-01-15).Google reference.5van Zalm, J.; Barroso, Browne, Casey, W.; Gordon, Henry, Kleinstreuer, N. C.; Lowit, Perron, Clippinger, Framework Establishing Methodologies. 2022, 96, 2865– 2879, 10.1007/s00204-022-03365-4 reference.6Burgoon, D.; Borgert, Comment ″Application Vitro Assay Identify Chemicals That Increase Estradiol Progesterone Synthesis Are Potential Breast Cancer Risk Factors. Health Perspect. 130, 058002, 10.1289/EHP11083 reference.7Cardona, Rudel, Application 2021, 129, 077003, 10.1289/EHP8608 Scholar7Application identify estradiol progesterone synthesis breast cancer factorsCardona, Bethsaida; Ruthann A.Environmental Perspectives (2021), 129 (7), 077003CODEN: EVHPAZ; ISSN:1552-9924. (U. Human Services, Institutes Health) BACKGROUND: Established factors, hormone replacement therapy reproductive history, thought act increasing estrogen (P4) activity. OBJECTIVE: We aimed chems. (E2) P4 evaluate risks. METHOD: Using high-throughput (HT) steroidogenesis Protection Agency (EPA) ToxCast program, we identified (E2-up) (P4-up) H295R adrenocortical carcinoma cells. prioritized compiled carcinogenicity reproductive/developmental (repro/dev) toxicity. exposure sources predicted intakes EPA's ExpoCast. RESULTS: found 296 E2 (182) (185), 71 both. often showed effects consistent mechanism. Of E2- P4-up chems., 30% likely repro/dev toxicants carcinogens, whereas 5-13% classified unlikely. most had insufficient effects. 45 assocd. mammary gland effects, also H294R assay, 29 P4, including well-known carcinogen 7,12-dimethylbenz(a)anthracene. pesticides, consumer ingredients, food additives, drinking water contaminants. DISCUSSION: hundred should considered because synthesis. helpful addn. current sensitive Relevant noticed dismissed, 2,4-dichlorophenol cyfluthrin. Fifty-three active E2-up 59 food, drugs evaluated carcinogenic priorities study redn. >> SciFinder ®https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhvVygtrY%253D&md5=cb32947de5bc2c8c5fa821945d125e9e8Rudel, Cardona, Borrel, Kay, E. "Application Factors". Environ 130 (5), 58003, 10.1289/EHP11400 reference.Cited By Click copied!This yet cited publications.Download PDFFiguresReferences Get e-AlertsGet e-AlertsJournal copied!https://doi.org/10.1021/acs.jafc.5c02930Published 2025© Views-Altmetric-Citations-Learn metrics closeArticle Views COUNTER-compliant sum text downloads since November 2008 (both PDF HTML) all institutions individuals. regularly updated usage leading up last few days.Citations number articles citing article, calculated Crossref daily. Find counts.The Altmetric Attention Score measure attention online. Clicking donut icon load page altmetric.com details score social media presence calculated.Recommended Articles FiguresReferencesAbstractHigh Resolution ImageDownload MS PowerPoint SlideReferences 5311There 2025-01-15).There 7Application reference.

Язык: Английский

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