New approach methodologies in human regulatory toxicology – Not if, but how and when!

Environment International, Год журнала: 2023, Номер 178, С. 108082 - 108082

Опубликована: Июль 4, 2023

The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk and ethics this system, demanding a change paradigm. At the same time, scientific toolbox used continuously enriched by development "New Approach Methodologies" (NAMs). While term does not define age or state readiness innovation, it covers wide range methods, including quantitative structure-activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models artificial intelligence (AI). In addition to promising faster more efficient toxicity testing, NAMs have potential fundamentally transform today's regulatory work allowing human-relevant decision-making in terms both hazard exposure assessment. Yet, several obstacles hamper broader application current Constraints addressing repeated-dose toxicity, with particular reference chronic hesitance from relevant stakeholders, are major challenges implementation context. Moreover, issues regarding predictivity, reproducibility quantification need be addressed legislative frameworks adapted NAMs. conceptual perspective presented here its focus on grounded main findings conclusions symposium workshop held Berlin November 2021. It intends provide further insights into how can gradually integrated aimed at protection health, until eventually paradigm replaced an animal-free "Next Generation Risk Assessment" (NGRA).

Язык: Английский

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Fast unmasking toxicity of safe personal care products

Journal of Chromatography A, Год журнала: 2025, Номер unknown, С. 465886 - 465886

Опубликована: Март 1, 2025

Язык: Английский

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Application of AOPs to assist regulatory assessment of chemical risks – Case studies, needs and recommendations

Environmental Research, Год журнала: 2022, Номер 217, С. 114650 - 114650

Опубликована: Окт. 26, 2022

While human regulatory risk assessment (RA) still largely relies on animal studies, new approach methodologies (NAMs) based in vitro, silico or non-mammalian alternative models are increasingly used to evaluate chemical hazards. Moreover, epidemiological studies with biomarkers of effect (BoE) also play an invaluable role identifying health effects associated exposures. To move towards the next generation (NGRA), it is therefore crucial establish bridges between NAMs and standard approaches, processes for increasing mechanistically-based biological plausibility studies. The Adverse Outcome Pathway (AOP) framework constitutes important tool address these needs but, despite a significant increase knowledge awareness, use AOPs RA remains limited. objective this paper issues related using context from various perspectives as was discussed workshop organized within European Union partnerships HBM4EU PARC spring 2022. presents examples where AOP has been proven useful process, particularly hazard prioritization characterization, integrated approaches testing (IATA), identification validation BoE Nevertheless, several limitations were identified that hinder optimal usability acceptance by community including lack quantitative information response-response relationships efficient ways map data (exposure toxicity) onto AOPs. summarizes suggestions, ongoing initiatives third-party tools may help overcome obstacles thus assure better implementation NGRA.

Язык: Английский

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ToxAIcology - The evolving role of artificial intelligence in advancing toxicology and modernizing regulatory science

ALTEX, Год журнала: 2023, Номер unknown, С. 559 - 570

Опубликована: Янв. 1, 2023

Язык: Английский

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Next Generation Risk Assessment approaches for advanced nanomaterials: Current status and future perspectives

NanoImpact, Год журнала: 2024, Номер 35, С. 100523 - 100523

Опубликована: Июль 1, 2024

This manuscript discusses the challenges of applying New Approach Methodologies (NAMs) for safe by design and regulatory risk assessment advanced nanomaterials (AdNMs). The authors propose a framework Next Generation Risk Assessment AdNMs involving NAMs that is aligned to conventional paradigm. exposure-driven, endpoint-specific, makes best use pre-existing information, can be implemented in tiers increasing specificity complexity adopted NAMs. tiered structure approach, which effectively combines existing data with targeted testing will allow safety assessed cost-effectively as far possible even more limited vertebrates. readiness state-of-the-art emerging terms Transparency, Reliability, Accessibility, Applicability, Relevance Completeness, their appropriateness discussed relation each step paradigm along providing perspectives future developments respective scientific areas.

Язык: Английский

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Revolutionizing developmental neurotoxicity testing – a journey from animal models to advanced in vitro systems

ALTEX, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Developmental neurotoxicity (DNT) testing has seen enormous progress over the last two decades. Preceding even publication of animal-based OECD test guideline for DNT in 2007, a series non-animal technology workshops and conferences (starting 2005) shaped community that delivered comprehensive battery vitro methods (IVB). Its data interpretation is covered by very recent guidance (No. 377). Here, we aim to overview field, focusing on evolution strategies, role emerging technologies, impact guidelines testing. In particular, this an example targeted development animal-free approach one most complex hazards chemicals human health. These developments started literally from blank slate, with no proposed alternative available. Over decades, cutting-edge science enabled design spares animals enables throughput challenging hazard. While it evident field needs regulation, massive economic decreased cognitive capacity caused chemical exposure should be prioritized more highly. Beyond this, claim fame scientific brought understanding brain, its development, how can perturbed. Plain language summaryDevelopmental predicts hazard brain development. Comprehensive advanced strategies using now replace approaches assess large numbers accurately efficiently than approach. Recent formalized DNT, marking pivotal achievement field. The shift towards reflects both commitment animal welfare growing recognition public health impacts associated impaired function exposures. innovations ultimately contribute safer management better protection health, especially during vulnerable stages

Язык: Английский

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Fast unmasking hazards of safe perfumes

Journal of Chromatography A, Год журнала: 2025, Номер unknown, С. 465959 - 465959

Опубликована: Апрель 1, 2025

Язык: Английский

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Chemical safety screening of products – better proactive

Journal of Chromatography A, Год журнала: 2025, Номер 1752, С. 465946 - 465946

Опубликована: Апрель 19, 2025

The increasing pressure to ensure product safety in a global market comes up against the current practice of targeting only known hazardous compounds analysis. However, refers not but also unknown or hidden hazards that are very important know and avoid. Shortcomings limitations currently used technologies seem cause an obvious discrepancy between intended actual consumer protection. Products as safe claimed by stakeholders. An existing overlooked proactive screening with prioritization strategy is brought into focus it offers unique solution. It can handle complexity thousands identity toxicity figure out compounds, both unknown. Using hardly any sample preparation effect detection at early position workflow game changer overlook compounds. All analytical needed, key re-arrangement instrument order, i.e. firstly hazard-related (effect first) secondly, on identification prioritized Such revealed previously products be safe. highly sustainable, affordable, all-in-one 2LabsToGo-Eco easy-to-use planar bioassays empowers stakeholders implement dynamic risk management. transition greater efficacy protection needs incentives critical review aims stimulate debate.

Язык: Английский

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A call for a Human Exposome Project

ALTEX, Год журнала: 2023, Номер unknown, С. 4 - 33

Опубликована: Янв. 1, 2023

Four decades of the Human Genome Project and its consequences have shown how entrepreneurial state, through significant investment into science, can drive scientific progress advance biomedicine. A certain fraction diseases now be explained as caused by genetics, a more impacted genetics. Besides another pathogens, third probably largest impactor is exposure, i.e., many physicochemical lifestyle factors. This article makes case that it time to start Exposome Project, which systematically explores catalogs exposure side human health disease.The envisioned needs than scaled exposomics approach, aiming assess totality relevant exposures ~omics body fluids forming hypotheses. Exposomics increasingly complemented science biomonitoring measure mechanistic understanding, human-relevant microphysiological systems, big data, artificial intelligence (AI) mine these data integrate pieces evidence. The potential impact AI on possible so substantial we should speak exposome (EI) because this allows us expand our limited current knowledge unknown unknowns threats health.

Язык: Английский

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Alternative methods go green! Green toxicology as a sustainable approach for assessing chemical safety and designing safer chemicals

ALTEX, Год журнала: 2024, Номер 41(1)

Опубликована: Янв. 1, 2024

Green toxicology is marching chemistry into the 21st century. This emerging framework will transform how chemical safety evaluated by incorporating evaluation of hazards, exposures, and risks associated with chemicals early product development in a way that minimizes adverse impacts on human environmental health. The goal to minimize toxic threats across entire supply chains through smarter designs policies. Traditional animal testing methods are replaced faster, cutting-edge innovations like organs-on-chips artificial intelligence predictive models also more cost-effective. Core principles green include utilizing alternative test methods, applying precautionary principle, considering lifetime impacts, emphasizing risk prevention over reaction. paper provides an overview these foundational concepts describes current initiatives future opportunities advance adoption approaches. Chal­lenges limitations discussed. shoots governments offering carrots European Deal nudge industry. Noteworthy, rights environ­mental groups have different ideas about needs for their consequences use. represents forward support both societal sufficient throughput relevance hazard information minimal suffering. toxi­cology thus sets stage synergize health ecological values. Overall, integration has potential profoundly shift managed achieve goals ethical, ecologically-conscious manner. Plain language summary aims make safer design. It focuses preventing toxicity issues during instead after products developed. uses modern non-animal computer lab tests cells predict if chem­icals could be hazardous. Benefits faster results, lower costs, less testing. using tests, caution even uncertain data, con­sidering global chains, article highlights US policy efforts spur sustainable innovation which necessitate greener approaches assess new materials drive adoption. seeks integrate design so valued equally functionality profit. alignment promises safer, ethical but faces chal­lenges around validating overcoming institutional resistance change.

Язык: Английский

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