A proposed screening strategy for evaluating the genotoxicity potential of botanicals and botanical extracts

Food and Chemical Toxicology, Год журнала: 2025, Номер unknown, С. 115277 - 115277

Опубликована: Янв. 1, 2025

Язык: Английский

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Comparative Study of Spheroids (3D) and Monolayer Cultures (2D) for the In Vitro Assessment of Cytotoxicity Induced by the Mycotoxins Sterigmatocystin, Ochratoxin A and Patulin

Foods, Год журнала: 2024, Номер 13(4), С. 564 - 564

Опубликована: Фев. 13, 2024

Mycotoxins are secondary metabolites produced by filamentous fungi associated with a variety of acute and chronic foodborne diseases. Current toxicology studies mainly rely on monolayer cell cultures animal models, which undeniably affected several limitations. To bridge the gap between current in vitro approach vivo predictability data, we here investigated cytotoxic effects induced mycotoxins sterigmatocystin (STE), ochratoxin A (OTA) patulin (PAT) different 2D 3D cultures. We focused human tumours (neuroblastoma SH-SY5Y cells epithelial breast cancer MDA-MB-213 cells) healthy (bone marrow-derived mesenchymal stem cells, BM-MSC, umbilical vein endothelial HUVECs). The cytotoxicity STE, OTA, PAT was determined after 24, 48 72 h exposure using an ATP assay both culture models. Three-dimensional spheroids’ morphology also analysed MATLAB-based open source software AnaSP 1.4 version. Our results highlight how each line models showed specific sensitivities, reinforcing importance more complex for multiple improved comprehensive risk assessment.

Язык: Английский

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Developing a pragmatic consensus procedure supporting the ICH S1B(R1) weight of evidence carcinogenicity assessment

Frontiers in Toxicology, Год журнала: 2024, Номер 6

Опубликована: Апрель 5, 2024

The ICH S1B carcinogenicity global testing guideline has been recently revised with a novel addendum that describes comprehensive integrated Weight of Evidence (WoE) approach to determine the need for 2-year rat study. In present work, experts from different organizations have joined efforts standardize as much possible procedural framework integration evidence associated S1B(R1) WoE criteria. uses pragmatic consensus procedure hazard assessment facilitate transparent, consistent, and documented decision-making it discusses best-practices both organization studies presentation data in format suitable regulatory review. First, is acknowledged six factors described form an network within holistic used synergistically analyze explain safety signals. Second, proposed standardized builds upon considerations related primary sources evidence, mechanistic analysis, alternative methodologies investigative approaches, metabolites, reliability other acquired information. Each highlighting how they can contribute overall assessment. A suggested reporting summarize cross-integration also presented. This work notes even if study ultimately required, creating valuable understanding specific levels human carcinogenic risk better than identified previously bioassay alone.

Язык: Английский

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New Approach Methodologies (NAMs) for safety testing of complex food matrices: A review of status, considerations, and regulatory adoption

Trends in Food Science & Technology, Год журнала: 2023, Номер 142, С. 104191 - 104191

Опубликована: Окт. 4, 2023

The conventional toxicological approach which primarily relies on animal testing has undergone several transformations in recent years due to limitations translational relevance, ethical and reproducibility concerns, high costs, time-consuming procedures. NAMs have emerged as alternative techniques that incorporate silico, chemico, vitro approaches provide mechanism-based insights with improved ethics human-relevant safety data. current landscape of employed for food risk assessments research regulatory settings is examined a focus their strengths, limitations, validation, standardisation, status. Furthermore, the challenges associated evaluation complex matrices are highlighted key considerations utilisation assessments. acceptance progressive majority demonstrating more relevance general chemical pharmaceutical cosmetics industries. There need advance approval address battery tests demonstrated applicable assessment matrices. review provides into status food-relevant identifies areas requiring adoption increase wider applicability.

Язык: Английский

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TKPlate 1.0: An Open‐access platform for toxicokinetic and toxicodynamic modelling of chemicals to implement new approach methodologies in chemical risk assessment

EFSA Journal, Год журнала: 2023, Номер 21(11)

Опубликована: Ноя. 1, 2023

This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8441/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8440/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8437/full

Язык: Английский

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Regulatory and practical considerations on the implementation of a mixture allocation factor in REACH

Environmental Sciences Europe, Год журнала: 2024, Номер 36(1)

Опубликована: Май 19, 2024

Abstract There is indisputable evidence that the environment, humans and wildlife are continuously exposed not to single but multiple chemicals from different sources. Exposure these mixtures can lead combined risks yet sufficiently addressed in any of European chemical legislations. Under REACH regulation for industrial chemicals, specific environmental mixture assessments challenged by a lack data on toxicity, use exposures communication along supply chain. Within Chemicals Strategy Sustainability Commission proposed introduce (a) allocation factor(s) (MAF) as regulatory management tool reduce exposures, effects potential unintentional mixtures. The MAF be applied default value within safety undertaken companies under REACH. Here, we critically review relevant literature discussing conceptual background approaches derive its magnitude. analysis focuses environment key issues an implementation practise together with remaining uncertainties needs possible ways forward. At this stage introducing Annex I appears most pragmatic immediately implementable measure address environment. A so-called ceiling preferred option policy makers, since it would only affect substances close their respective risk threshold. While magnitude will decided politically, choice methods assumptions size should clear transparent, build available scientific take account uncertainties. effective reducing releases exposure levels if mitigation measures implemented practise. Its socioeconomic impacts costs need assessed balanced way benefits society, companies—also comparison efforts needed assessments. In future experiences gathered practise, discussion how assess regulate across pieces legislation consider true situation ensure harmonisation.

Язык: Английский

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Occurrence of the two major regulated mycotoxins, ochratoxin A and fumonisin B1, in cereal and cereal-based products in Europe and toxicological effects: A review

Environmental Toxicology and Pharmacology, Год журнала: 2024, Номер 109, С. 104489 - 104489

Опубликована: Июнь 5, 2024

Among cereal contaminants, mycotoxins are of concern due to their importance in terms food and feed safety. The difficulty establishing a diagnosis for mycotoxicosis relies on the fact that effects most often subclinical chronic exposure common scenario is multi-contamination by various toxins. Mycotoxin co-occurrence major safety as additive or even synergic toxic impacts may occur, but also regarding current regulations they mainly individual mycotoxin levels specific foods chain. However, large number possible combinations, there still limited knowledge co-exposure toxicity data, which depends several parameters. In this context, systematic review aims provide an overview two regulated mycotoxins, namely ochratoxin A fumonisin B1. This focused 2012 2022 period analysed occurrence Europe selected different matrices (cereals cereal-derived products), impact, alone combination, vitro intestinal hepatic human cells. To better understand evaluate associated risks, further research needed using new approach methodologies (NAM), such 3D models. Cereals derived products important source humans animals worldwide. manuscript state art literature over last ten years B1 these well toxicological effects, Future perspectives some challenges assessment discussed.

Язык: Английский

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Next generation risk assessment for occupational chemical safety – A real world example with sodium-2-hydroxyethane sulfonate

Toxicology, Год журнала: 2024, Номер 506, С. 153835 - 153835

Опубликована: Июнь 8, 2024

Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted assessments consumer use cosmetics and not currently implemented in occupational assessments, e.g. under EU REACH. By contrast, a large proportion regulatory worker are underpinned by toxicological studies using experimental animals. Consequently, represents area would benefit from increasing application decision making. Here, workflow for conducting context was developed, which illustrated with case study chemical; sodium 2-hydroxyethane sulphonate (sodium isethionate or SI). Exposures were estimated standard exposure model following comprehensive life cycle SI considering factory-specific data. Outputs this then used estimate internal exposures Physiologically Based Kinetic (PBK) model, constructed specific Absorption, Distribution, Metabolism Excretion (ADME) PBK modelling indicated worst-case plasma maximum concentration (Cmax) 0.8 μM across the cycle. bioactivity assessed battery NAMs relevant systemic, reproductive, developmental toxicity; cell stress panel, high throughput transcriptomics three lines (HepG2, HepaRG MCF-7 cells), pharmacological profiling assays relating toxicity (Reprotracker devTOX quickPredict). Points Departure (PoDs) ranged 104 5044 µM. Cmax values obtained compared PoDs derive Bioactivity Exposure Ratios (BERs) demonstrated workers exposed current levels factory risk management. In summary, tiered iterative developed here opportunity integrating non animal approaches subset substances systemic required. Such could be followed ensure testing only conducted as "last resort"

Язык: Английский

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Human‐based new approach methodologies to accelerate advances in nutrition research

Food Frontiers, Год журнала: 2024, Номер 5(3), С. 1031 - 1062

Опубликована: Март 5, 2024

Abstract Much of nutrition research has been conventionally based on the use simplistic in vitro systems or animal models, which have extensively employed an effort to better understand relationships between diet and complex diseases as well evaluate food safety. Although these models undeniably contributed increase our mechanistic understanding basic biological processes, they do not adequately model human physiopathological phenomena, creating concerns about translatability humans. During last decade, extraordinary advancement stem cell culturing, three‐dimensional cultures, sequencing technologies, computer science occurred, originated a wealth novel human‐based more physiologically relevant tools. These tools, also known “new approach methodologies,” comprise patient‐derived organoids, organs‐on‐chip, multi‐omics approach, along with computational analysis, represent innovative exciting tools forward from human‐biology‐oriented perspective. After considering some shortcomings conventional vivo approaches, here we describe main available emerging that are appropriate for designing human‐relevant research. Our aim is encourage discussion opportunity explore paths promote paradigm‐change toward biology‐focused nutritional pathophysiology, products, develop effective targeted preventive therapeutic strategies while helping reducing number replacing animals

Язык: Английский

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A perspective review on factors that influence mutagenicity in medicinal plants and their health implications

Toxicological Sciences, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Medicinal plants are products from natural sources that have found relevance in medicine for several decades. They rich bioactive compounds; thus, they widely used to treat different ailments globally. provided hope the health care industry as most synthesize modern medicines currently treatment of various diseases. However, there still concerns with respect mutagenic properties medicinal plants. Over years, researchers embarked on studies aimed at investigating mutagenicity regions world. In this review, we discussed factors may influence plant and findings in-vitro in-vivo across globe. addition, review considers potential implications safety measures can be mitigate mutagenesis plant. To achieve this, searched articles reporting PubMed, Scopus Web Science databases. Several journal reported some plants; however, it was observed majority non-mutagenicity The these implies good prospects treating diseases clinically relevant. reports will require further validation determine their human use limited were conducted no clinical any review.

Язык: Английский

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