New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project

Frontiers in Toxicology, Год журнала: 2024, Номер 6

Опубликована: Апрель 26, 2024

In the European regulatory context, rodent in vivo studies are predominant source of neurotoxicity information. Although they form a cornerstone neurotoxicological assessments, costly and topic ethical debate. While public expects chemicals products to be safe for developing mature nervous systems, considerable numbers commerce have not, or only limited extent, been assessed their potential cause neurotoxicity. As such, there is societal push toward replacement animal models with vitro alternative methods. New approach methods (NAMs) can contribute knowledge base, increase chemical safety, modernize hazard risk assessment. Provided reach an acceptable level relevance reliability, NAMs may considered as replacements specific studies. The Partnership Assessment Risks from Chemicals (PARC) addresses challenges development implementation collaboration agencies, Project 5.2.1e (Neurotoxicity) aims develop evaluate developmental (DNT) adult (ANT) understand applicability domain detection endocrine disruption epigenetic perturbation. To speed up assay time reduce costs, we identify early indicators later-onset effects. Ultimately, will assemble second-generation first-generation test batteries, both which aim provide assessors industry stakeholders robust, speedy, lower-cost, informative next-generation assessment tools.

Язык: Английский

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Progress in toxicogenomics to protect human health

Nature Reviews Genetics, Год журнала: 2024, Номер unknown

Опубликована: Сен. 2, 2024

Язык: Английский

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Addressing the safety of new food sources and production systems

Comprehensive Reviews in Food Science and Food Safety, Год журнала: 2024, Номер 23(3)

Опубликована: Май 1, 2024

Abstract New food sources and production systems (NFPS) are garnering much attention, driven by international trade, changing consumer preferences, potential sustainability benefits, innovations in climate‐resilient systems. However, NFPS can introduce new challenges for safety agencies manufacturers. Most hazards linked to foods have been identified traditional foods. there be some that unique ingredients, inputs, processes unexpected contaminants. To realize the full of NFPS, is a need stakeholders from governments, industry, research community collectively work address communicate products. This review outlines known associated with select products on market, namely, plant‐derived proteins, seaweeds, jellyfish, insects, microbial as well derived cell‐based production, precision fermentation, vertical farming, 3D printing. We identify common elements emerging regulatory frameworks various countries/regions. Furthermore, we highlight current efforts harmonization terminologies, use recent scientific tools fill knowledge gaps, multi‐stakeholder collaborations tackle challenges. Although cannot one‐size‐fits‐all approach when it comes oversight ensuring develop consensus‐based structured protocols or workflows among facilitate comprehensive, robust, internationally harmonized approaches. These increase consumers’ confidence contribute toward fair practices trade such

Язык: Английский

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Optimizing Chemicals Management in the United States and Canada through the Essential-Use Approach

Environmental Science & Technology, Год журнала: 2023, Номер 57(4), С. 1568 - 1575

Опубликована: Янв. 19, 2023

Chemicals have improved the functionality and convenience of industrial consumer products, but sometimes at expense human or ecological health. Existing regulatory systems proven to be inadequate for assessing managing tens thousands chemicals in commerce. A different approach is urgently needed minimize ongoing production, use, exposures hazardous chemicals. The premise essential-use that concern should used only cases which their function specific products necessary health, safety, functioning society when feasible alternatives are unavailable. To optimize broader implementation United States Canada, we recommend governments businesses (1) identify essentiality assessments based on a broad range hazard traits, going beyond toxicity; (2) expedite decision-making by avoiding unnecessary strategically asking up three questions determine whether use chemical product essential; (3) apply as early possible process developing chemicals; (4) engage diverse experts identifying uses functions, alternatives, making determinations share such information broadly. If optimized expanded into other policymaking bodies, businesses, can improve management shift market toward safer chemistries benefit

Язык: Английский

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Comparing LD₅₀/LC₅₀ Machine Learning Models for Multiple Species

ACS Chemical Health & Safety, Год журнала: 2023, Номер 30(2), С. 83 - 97

Опубликована: Фев. 23, 2023

The lethal dose or concentration which kills 50% of the animals (LD50 LC50) is an important parameter for scientists to understand toxicity chemicals in different scenarios that can be used make go-no-go decisions, and ultimately assist choice right personal protective equipment needed containment. LD50 assessment process has also required use many although modern methods have reduced number rats needed. Since a compound usually considered highly toxic when lower than 25 mg/kg, such classification provides potentially valuable safety information synthetic chemists other scientists. need finding alternative approaches as computational reduce animal this testing further still. We now summarize our efforts public data building vivo LC50 regression machine learning models various species (rat, mouse, fish, daphnia) their fivefold cross-validation statistics with algorithms well external curated test set mouse LD50. These datasets consist molecule classes, may cover activity ranges, range dataset sizes. challenges using are applicability domain will understood so they reliable predictions novel molecules. backed up experimental validation. However, could bridge gaps individual datasets. Making available opens them potential misuse dual use. these propose scoring millions commercially molecules, most likely do not known matter any vitro toxicity.

Язык: Английский

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Wildlife ecological risk assessment in the 21st century: Promising technologies to assess toxicological effects

Integrated Environmental Assessment and Management, Год журнала: 2023, Номер 20(3), С. 725 - 748

Опубликована: Июль 7, 2023

Despite advances in toxicity testing and the development of new approach methodologies (NAMs) for hazard assessment, ecological risk assessment (ERA) framework terrestrial wildlife (i.e., air-breathing amphibians, reptiles, birds, mammals) has remained unchanged decades. While survival, growth, reproductive endpoints derived from whole-animal tests are central to nonstandard measures biological effects at multiple levels organization (e.g., molecular, cellular, tissue, organ, organism, population, community, ecosystem) have potential enhance relevance prospective retrospective ERAs. Other factors indirect contaminants on food supplies infectious disease processes) influenced by toxicants individual, community levels, need be factored into chemically based assessments "eco" component Regulatory logistical challenges often relegate such postregistration evaluations pesticides industrial chemicals contaminated site evaluations. NAMs being developed, date, their applications ERAs focused been limited. No single magic tool or model will address all uncertainties assessment. Modernizing likely entail combinations laboratory- field-derived data organization, knowledge collection solutions systematic review, adverse outcome pathway frameworks), inferential methods that facilitate integrations estimations species, populations, interspecific extrapolations, ecosystem services modeling, with less dependence simple ratios. Integr Environ Assess Manag 2024;20:725-748. © 2023 His Majesty King Right Canada The Authors. Integrated Environmental Assessment Management published Wiley Periodicals LLC behalf Society Toxicology & Chemistry (SETAC). Reproduced permission Minister Environment Climate Change Canada. This article contributed US Government employees work is public domain USA.

Язык: Английский

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A vision for safer food contact materials: Public health concerns as drivers for improved testing

Environment International, Год журнала: 2023, Номер 180, С. 108161 - 108161

Опубликована: Сен. 26, 2023

Food contact materials (FCMs) and food articles are ubiquitous in today's globalized system. Chemicals migrate from FCMs into foodstuffs, so called chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health hazardous FCCs because only individual substances used to make tested mostly for genotoxicity while endocrine disruption other hazard properties disregarded. Indeed, a known source of wide range chemicals, they likely contribute highly prevalent non-communicable diseases. can also include non-intentionally added (NIAS), which often unknown therefore subject risk assessment. To address these important shortcomings, we outline how the safety may be improved by (1) testing overall migrate, including (unknown) NIAS, finished articles, (2) expanding toxicological beyond multiple endpoints associated with diseases relevant human health. identify mechanistic testing, group chronic outcomes chemical exposure Six Clusters Disease (SCOD) propose that should their impacts on SCOD. Research focus developing robust, relevant, sensitive in-vitro assays based information linked SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics Toxicants. Implementing this vision will improve prevention exposures, FCMs.

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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Toxicological effects assessment for wildlife in the 21st century: Review of current methods and recommendations for a path forward

Integrated Environmental Assessment and Management, Год журнала: 2023, Номер 20(3), С. 699 - 724

Опубликована: Июнь 1, 2023

Model species (e.g., granivorous gamebirds, waterfowl, passerines, domesticated rodents) have been used for decades in guideline laboratory tests to generate survival, growth, and reproductive data prospective ecological risk assessments (ERAs) birds mammals, while officially adopted assessment schemes amphibians reptiles do not exist. There are recognized shortcomings of current vivo methods as well uncertainty around the extent which with different life histories terrestrial amphibians, reptiles, bats) than these commonly models protected by existing ERA frameworks. Approaches other validating additional animal testing being developed, but incorporation such new approach methodologies (NAMs) into frameworks will require robust validations against responses. This takes time, ability extrapolate findings from nonanimal studies organism- population-level effects wildlife remains weak. Failure adequately anticipate predict hazards could economic potentially even legal consequences regulators product registrants. In order be able use fewer animals or replace them altogether long term, vertebrate whole organism needed provide NAM validation short term. Therefore, it is worth investing resources potential updates standard test guidelines addressing need clear guidance on conduct field studies. Herein, we review improving advancing assessment, tools foreseeable future. Integr Environ Assess Manag 2024;20:699-724. © 2023 His Majesty King Right Canada The Authors. Integrated Environmental Assessment Management published Wiley Periodicals LLC behalf Society Toxicology & Chemistry (SETAC). Reproduced permission Minister Environment Climate Change Canada. article has contributed U.S. Government employees their work public domain USA.

Язык: Английский

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Potential for Machine Learning to Address Data Gaps in Human Toxicity and Ecotoxicity Characterization

Environmental Science & Technology, Год журнала: 2023, Номер 57(46), С. 18259 - 18270

Опубликована: Ноя. 1, 2023

Machine Learning (ML) is increasingly applied to fill data gaps in assessments quantify impacts associated with chemical emissions and chemicals products. However, the systematic application of ML-based approaches still limited, their potential for addressing a wide range unknown. We prioritized chemical-related parameters toxicity characterization inform ML model development based on two criteria: (1) each parameter's relevance robustly characterize described by uncertainty results attributable parameter (2) predict values availability measured data. 13 out 38 developing approaches, while flagging another nine critical gaps. For all parameters, we performed space analysis assess further diverse considering structural diversity available data, showing that can potentially 8–46% marketed 1–10% Our systematically future efforts address characterization.

Язык: Английский

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