Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

EFSA Journal, Journal Year: 2019, Volume and Issue: 17(3)

Published: March 1, 2019

This Guidance document describes harmonised risk assessment methodologies for combined exposure to multiple chemicals all relevant areas within EFSA's remit, i.e. human health, animal health and ecological areas. First, a short review of the key terms, scientific basis approaches assessing (eco)toxicology is given, including existing frameworks these assessments. background was evaluated, resulting in framework chemicals. The based on steps (problem formulation, assessment, hazard identification characterisation, characterisation uncertainty analysis), with tiered stepwise both whole mixture component-based approaches. Specific considerations are given grouping into common groups, use dose addition as default assumption, integrate evidence interactions refinement groups. Case studies annexed this guidance explore feasibility spectrum applications proposed methods assessment. Scientific Committee considers that fit purpose assessments should be applied work. Future work research recommended.

Language: Английский

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Use of Zebrafish in Drug Discovery Toxicology

Chemical Research in Toxicology, Journal Year: 2019, Volume and Issue: 33(1), P. 95 - 118

Published: Oct. 18, 2019

Unpredicted human safety events in clinical trials for new drugs are costly terms of health and money. The drug discovery industry attempts to minimize those with diligent preclinical testing. Current standard practices good at preventing toxic compounds from being tested the clinic; however, false negative toxicity results still a reality. Continual improvement must be pursued realm. Higher-quality therapies can brought forward more information about potential toxicities associated mechanisms. zebrafish model is bridge between vitro assays mammalian vivo studies. This powerful its breadth application tractability research. In past two decades, our understanding disease biology has grown significantly owing thousands studies on this tiny vertebrate. Review summarizes challenges strengths model, discusses 3Rs value that it deliver, highlights translatable untranslatable biology, brings together reports recent focusing toxicology.

Language: Английский

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Exploring BPA alternatives – Environmental levels and toxicity review

Environment International, Journal Year: 2024, Volume and Issue: 189, P. 108728 - 108728

Published: May 23, 2024

Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol (BPA) that offer similar functionality. These already in the market, entering environment and thus raising ecological concerns. However, it can be expected levels BPA will dominate future, they limited information on their environmental safety. The EU PARC project highlights priority chemicals consolidates alternatives, with a focus relevance identification research gaps. review highlighted aspects future perspectives. In brief, an extension monitoring is crucial, extending to cover track facilitate timely implementation mitigation measures. biological activity has been studied for but non-systematic way prioritized number chemicals. For several data provided substantial evidence regarding potential harm environment. We stress importance conducting more comprehensive assessments go beyond traditional reproductive studies overlooked relevant endpoints. Future should also consider mixture effects, realistic concentrations, long-term consequences biota ecosystems.

Language: Английский

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The posterity of Zebrafish in paradigm of in vivo molecular toxicological profiling

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116160 - 116160

Published: Jan. 21, 2024

The aggrandised advancement in utility of advanced day-to-day materials and nanomaterials has raised serious concern on their biocompatibility with human other biotic members. In last few decades, understanding toxicity these been given the centre stage research using many vitro vivo models. Zebrafish (Danio rerio), a freshwater fish member minnow family garnered much attention due to its distinct features, which make it an important frequently used animal model various fields embryology toxicological studies. Given that fertilization development zebrafish eggs take place externally, they serve as excellent organism for studying early developmental stages. Moreover, possess comparable genetic composition humans share almost 70% genes mammals. This particular become increasingly popular, especially research. serves link between studies analysis It is appealing choice vertebrate research, when employing high-throughput methods, small size, swift development, relatively affordable laboratory setup. enhanced comprehension pathobiology drug toxicity. review emphasizes recent developments screening assays, new insights gained about drugs through assays. Specifically, cardio, neural, and, hepatic toxicology inferred by applications nanoparticles have highlighted.

Language: Английский

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Chemical risk assessment in food animals via physiologically based pharmacokinetic modeling − Part I: Veterinary drugs on human food safety assessment

Environment International, Journal Year: 2025, Volume and Issue: 197, P. 109339 - 109339

Published: Feb. 18, 2025

Language: Английский

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Tissue-Specific Accumulation, Biotransformation, and Physiologically Based Toxicokinetic Modeling of Benzotriazole Ultraviolet Stabilizers in Zebrafish (Danio rerio)

Environmental Science & Technology, Journal Year: 2021, Volume and Issue: 55(17), P. 11874 - 11884

Published: Aug. 17, 2021

Benzotriazole ultraviolet stabilizers (BUVSs) are high-production-volume chemicals with ubiquitous occurrence in the aquatic environment. However, little is known about their bioconcentration and biotransformation, physiologically based toxicokinetic (PBTK) models for BUVSs lacking. This study selected six which experiments were performed zebrafish (Danio rerio) exposed to two different levels (0.5 10 μg·L–1). Higher kinetic factors (BCFs) observed at lower exposure level environmental relevance, BCF of 3.33 × 103 L·kg–1 2-(2-hydroxy-3,5-di-tert-butylphenyl)-5-chlorobenzotriazole (UV-327). phenomenon was interpreted by a nonlinear adsorption mechanism, where binding specific protein sites contributes bioconcentration. Muscle exhibited lowest accumulation, depuration half-life UV-327 19.5 d. In kidney, muscle, ovary, gill, skin, logBCF increased increase log KOW until ca. 6.5, above decreased. trend not liver intestine. Six biotransformation products identified mainly accumulated Considering mechanism PBTK model, prediction accuracy model improved, highlighting xenobiotics assessing risk assessment.

Language: Английский

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Implementing New Approach Methodologies (NAMs) in food safety assessments: Strategic objectives and actions taken by the European Food Safety Authority

Trends in Food Science & Technology, Journal Year: 2023, Volume and Issue: 133, P. 277 - 290

Published: Feb. 8, 2023

New Approach Methodologies (NAMs) comprise in silico and vitro methods applied as alternative to animal testing. Even though NAMs are already fully implemented research tools, their use regulatory risk assessments (RA) is limited currently. To promote the uptake/acceptance of NAMs, a paradigm shift assessment approaches, proper dialogue between assessors managers needed. Several reviews addressed for chemical RA generic terms, but without providing specific considerations on food/feed safety assessments. Therefore, this review, we give insights potential purposes EU. We summarise relevant projects activities coordinated by European Food Safety Authority (EFSA), which agency Union that contributes food feed chain. The review informs future developments human health RA, touches protein toxicity allergenicity, well environmental risks. Reducing testing filling some gaps via almost reality. Moreover, there growing body evidence confirming inclusion mechanistic information improves EFSA's address main challenge using intermediate effects observed non-animal models assessments, especially those linked adverse insufficiently covered or uncovered apical endpoints.

Language: Английский

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EFSA’s OpenFoodTox: An open source toxicological database on chemicals in food and feed and its future developments

Environment International, Journal Year: 2020, Volume and Issue: 146, P. 106293 - 106293

Published: Dec. 8, 2020

Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances >2000 Scientific Opinions, Statements and Conclusions through work of Panels, Units Committee. OpenFoodTox is an open source toxicological database, available both download data visualisation which provides all evaluated by EFSA including substance characterisation, links to EFSA's outputs, applicable legislations regulations, a summary hazard identification characterisation human health, animal health ecological assessments. The database been structured using OECD harmonised templates reporting chemical test summaries (OHTs) facilitate sharing with stakeholders interest assessment, such as sister agencies, international scientific advisory bodies, others. This manuscript description model, content tools search database. Examples applications assessment are discussed new quantitative structure–activity relationship (QSAR) models, integration into (OECD QSAR Toolbox AMBIT-2.0), environmental footprints testing threshold concern (TTC) values food related compounds. Finally, future developments 2.0 include properties, physico-chemical exposure data, toxicokinetic information; within silico modelling platforms models physiologically-based kinetic models. Such vivo, vitro provide different lines evidence can be assembled, weighed integrated Weight Evidence approaches support use New Approach Methodologies (NAMs) reduction testing.

Language: Английский

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Muscle Glycogen Phosphorylase and Its Functional Partners in Health and Disease

Cells, Journal Year: 2021, Volume and Issue: 10(4), P. 883 - 883

Published: April 13, 2021

Glycogen phosphorylase (PG) is a key enzyme taking part in the first step of glycogenolysis. Muscle glycogen (PYGM) differs from other PG isoforms expression pattern and biochemical properties. The main role PYGM providing sufficient energy for muscle contraction. However, it expressed tissues than muscle, such as brain, lymphoid tissues, blood. important not only metabolism, but also diverse processes insulin glucagon signaling pathway, resistance, necroptosis, immune response, phototransduction. implicated several pathological states, deficiency (McArdle disease), schizophrenia, cancer. Here we attempt to analyze available data regarding protein partners shed light on its possible interactions functions. We underline potential zebrafish become convenient applicable model study functions, especially because unique features that can complement obtained approaches.

Language: Английский

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The Zebrafish Xenograft Models for Investigating Cancer and Cancer Therapeutics

Biology, Journal Year: 2021, Volume and Issue: 10(4), P. 252 - 252

Published: March 24, 2021

In order to develop new cancer therapeutics, rapid, reliable, and relevant biological models are required screen validate drug candidates for both efficacy safety. recent years, the zebrafish (Danio rerio) has emerged as an excellent model organism suited these goals. Larval fish or immunocompromised adult used engraft human cells serve a platform screening potential candidates. With sharing ~80% of disease-related orthologous genes with humans, they provide low cost, high-throughput alternative mouse xenografts that is biology. this review, we background on methods utility xenograft in research.

Language: Английский

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