Advances on carbon nanomaterials and their applications in medical diagnosis and drug delivery

Colloids and Surfaces B Biointerfaces, Journal Year: 2024, Volume and Issue: 241, P. 114032 - 114032

Published: June 13, 2024

Language: Английский

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The Critical Role of Commercial Analytical Reference Standards in the Control of Chemical Risks: The Case of PFAS and Ways Forward

Environmental Health Perspectives, Journal Year: 2025, Volume and Issue: 133(1)

Published: Jan. 1, 2025

Various countries have instituted risk governance measures to control and minimize the risks of chemicals at national international levels. Activities typically include assessment based on a) hazard exposure assessments; b) setting limits production, use, emissions chemicals; c) enforcement regulations; d) monitoring effectiveness taken. These steps largely depend chemical analysis access pure reference standards. However, except for specific highly regulated categories chemicals, such standards often are not commercially available. This raises a critical question: Given widespread lack standards, is current approach governing adequate protect humans environment from harm? If not, what could be taken improve situation? We outline how hampered by produce required scientific evidence. also provide list recommendations controlling in absence use per- polyfluoroalkyl substances (PFASs), specifically C6O4 [perfluoro ([5-methoxy-1,3-dioxolan-4-yl]oxy) acetic acid], illustrate companies that can prevent argue very limited availability undermines ability scientists independent evidence needed and, thereby, prevents society protecting people against pollution its harms. Possible ways situation guaranteeing creating repository, redefining level confidence sufficient regulatory action, providing alternative options identification quantification when available, considering, no regulation class rather than individually. https://doi.org/10.1289/EHP12331.

Language: Английский

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A Transformative Vision for an Omics-Based Regulatory Chemical Testing Paradigm

Toxicological Sciences, Journal Year: 2022, Volume and Issue: 190(2), P. 127 - 132

Published: Sept. 27, 2022

Use of molecular data in human and ecological health risk assessments industrial chemicals agrochemicals has been anticipated by the scientific community for many years; however, these are rarely used assessment. Here, a logic framework is proposed to explore feasibility future development transcriptomic methods refine replace current apical endpoint-based regulatory toxicity testing paradigm. Four foundational principles outlined discussed that would need be accepted stakeholders prior this transformative vision being realized. Well-supported knowledge, first principle transcriptomics reliable tool detecting alterations gene expression result from endogenous or exogenous influences on test organism. The second states indicators adverse adaptive biological responses stressors an Principle 3 can employed establish benchmark dose-based point departure (POD) short-term, vivo studies at dose level below which concerted change (CMC) not expected. Finally, 4 use POD (set CMC level) will support health-protective If all four substantiated, expected transform aspects chemical agrochemical assessment process focused establishing safe exposure levels mammals across numerous toxicological contexts resulting significant reduction animal while providing equal greater protection health. Importantly, approaches also generally applicable safety

Language: Английский

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Advancing the 3Rs: innovation, implementation, ethics and society

Frontiers in Veterinary Science, Journal Year: 2023, Volume and Issue: 10

Published: June 15, 2023

The 3Rs principle of replacing, reducing and refining the use animals in science has been gaining widespread support international research community appears transnational legislation such as European Directive 2010/63/EU, a number national legislative frameworks like Switzerland UK, other rules guidance place countries around world. At same time, progress technical biomedical research, along with changing status many societies, challenges view sufficient effective approach to moral set by animal research. Given this growing awareness our responsibilities animals, aim paper is address question: Can 3Rs, policy instrument for still guide morally acceptable scientific purposes, if so, how? fact that increased availability alternatives models not correlated inversely decrease used led public political calls more radical action. However, focus on simple measure total numbers distracts from need nuanced understanding how can have genuine influence guiding testing. Hence, we three core dimensions contemporary research: (1) What

Language: Английский

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From vision toward best practices: Evaluating in vitro transcriptomic points of departure for application in risk assessment using a uniform workflow

Frontiers in Toxicology, Journal Year: 2023, Volume and Issue: 5

Published: May 23, 2023

The growing number of chemicals in the current consumer and industrial markets presents a major challenge for regulatory programs faced with need to assess potential risks they pose human ecological health. increasing demand hazard risk assessment currently exceeds capacity produce toxicity data necessary decision making, applied is commonly generated using traditional approaches animal models that have limited context terms relevance. This scenario provides opportunity implement novel, more efficient strategies purposes. study aims increase confidence implementation new approach methods by parallel analysis identify gaps experimental designs, reveal limitations common deriving transcriptomic points departure, demonstrate strengths high-throughput transcriptomics (HTTr) derive practical endpoints. A uniform workflow was across six curated gene expression datasets from concentration-response studies containing 117 diverse chemicals, three cell types, range exposure durations, determine tPODs based on profiles. After benchmark concentration modeling, used consistent reliable tPODs. High-throughput toxicokinetics were employed translate vitro (µM) human-relevant administered equivalent doses (AEDs, mg/kg-bw/day). most had AEDs lower (i.e., conservative) than apical PODs US EPA CompTox chemical dashboard, suggesting would be protective effects An multiple single revealed longer duration varied culture systems (e.g., 3D vs. 2D) lead decreased tPOD value indicated increased potency. Seven flagged as outliers when comparing ratio POD, thus indicating require further better understand their potential. Our findings build use but also must addressed prior adoption support applications.

Language: Английский

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Status, implications and challenges of European safe and sustainable by design paradigms applicable to nanomaterials and advanced materials

RSC Sustainability, Journal Year: 2023, Volume and Issue: 1(2), P. 234 - 250

Published: Jan. 1, 2023

Current European (EU) policies, such as the Green Deal, envisage safe and sustainable by design (SSbD) practices for management of chemicals, which cogently entail nanomaterials (NMs) advanced materials (AdMa).

Language: Английский

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Bioactive limonoids from Carapa guianensis seeds oil and the sustainable use of its by-products

Current Research in Toxicology, Journal Year: 2023, Volume and Issue: 4, P. 100104 - 100104

Published: Jan. 1, 2023

Carapa guianensis (Andiroba, Meliaceae) is considered a multipurpose tree. In Brazil, Indigenous people have used it as insect repellent and in the treatment of various diseases. Most biological activities popular uses are attributed to limonoids, which highly oxygenated tetranortriterpenoids. More than 300 limonoids been described Meliaceae family. Limonoids from Andiroba oil shown high anti-inflammatory anti-allergic vivo, by inhibiting platelet activating factors many inflammatory mediators such IL-5, IL-1β TNF-α. It also reduced T lymphocytes, eosinophils mast cells. corroboration with wide use oil, no significant cytotoxicity or genotoxicity vivo was reported. This promotes apoptosis gastric cancer cell line (ACP02) at concentrations, without showing mutagenic effects, suggested increase body's nonspecific resistance adaptive capacity stressors, exhibit some antioxidant activity, protect against oxidative DNA damages. Recently, new methodologies toxicological assays applied. They include chemico, vitro, silico ex procedures, take place substitute laboratory animals. by-products sustainable production processes fertilizers soil conditioners, raw material for soap production, biodegradable surfactants an alternative natural source polymer order reduce environmental impacts. review reinforces relevance highlights its ability add value minimize possible risks health Amazonian population.

Language: Английский

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A pragmatic framework for the application of new approach methodologies in one health toxicological risk assessment

Toxicological Sciences, Journal Year: 2023, Volume and Issue: 192(2), P. 155 - 177

Published: Feb. 14, 2023

Globally, industries and regulatory authorities are faced with an urgent need to assess the potential adverse effects of chemicals more efficiently by embracing new approach methodologies (NAMs). NAMs include cell tissue methods (in vitro), structure-based/toxicokinetic models silico), that toxicant interactions biological macromolecules chemico), alternative models. Increasing knowledge on chemical toxicokinetics (what body does chemicals) toxicodynamics do body) obtained from in silico vitro systems continues provide opportunities for modernizing risk assessments. However, directly leveraging data derivation human health-based reference values has not received acceptance due uncertainties extrapolating NAM results populations, including metabolism, complex pathways, multiple exposures, interindividual susceptibility vulnerable populations. The objective this article is a standardized pragmatic framework applies integrated approaches focus quantitative vivo extrapolation (QIVIVE) extrapolate cellular exposures equivalent doses which can be derived. proposed intends systematically account complexities interpretation support sound health safety decisions diverse industrial sectors (food systems, cosmetics, chemicals, pharmaceuticals etc.). Case studies entities, using existing data, presented demonstrate utility while highlighting sources population bias uncertainty, importance Good Method Reporting Practices.

Language: Английский

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Chemical and in vitro toxicological comparison of emissions from a heated tobacco product and the 1R6F reference cigarette

Toxicology Reports, Journal Year: 2023, Volume and Issue: 10, P. 281 - 292

Published: Jan. 1, 2023

It has previously been found that, compared with cigarette smoke, the aerosols generated by heated tobacco products contain fewer and lower harmful potentially constituents (HPHCs) elicit biological activity in vitro models smoking-related exposure biomarker levels clinical studies. is important to accumulate such scientific evidences for a novel heating system, because different system may affect quantitative aspect of amount HPHCs qualitative aerosol generated. Here, chemical properties of, toxicological responses emitted DT3.0a, new product smoke (CS) were compared, using analyses, battery (standardized genotoxicity cytotoxicity) assays, mechanistic (ToxTracker two-dimensional cell culture) assays. Regular- menthol-flavored DT3.0a standard 1R6F reference cigarettes tested. Selected HPHC yields than CS. The genotoxicity-related assays indicated that was not genotoxic, regardless metabolic activation. other less cytotoxicity induction oxidative stress response elicited Similar results both regular menthol DT3.0a. Like previous reports systems, this study have likely be

Language: Английский

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A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 6, 2023

Prolonged exposure to environmental respirable toxicants can lead the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) fibrosis. The limited number FDA-approved inhaled drugs for these serious lung conditions has led a shift from in vivo towards use alternative vitro human-relevant models better predict toxicity particles preclinical research. While there are several inhalation upper airways, fragile dynamic nature alveolar microenvironment reproducible distal lung. Here, we present mechanistic approach using new generation systems, Cloud α AX12. This novel tool consists cloud-based chamber (VITROCELL) that integrates breathing AX Lung-on-chip system (AlveoliX). ultrathin porous membrane AX12 plate was used create complex multicellular model enables key physiological culture conditions: air-liquid interface (ALI) three-dimensional cyclic stretch (CS). Human-relevant cellular were established a) alveolar-capillary primary cell-derived immortalized epithelial cells ( iAECs), macrophages (THP-1) endothelial (HLMVEC) cells, b) upper-airways Calu3 cells. Primary human hAEpCs) validate results obtained cell lines. To mimic relevant aerosol exposures with AX12, three different using: titanium dioxide (TiO2) zinc oxide nanoparticles polyhexamethylene guanidine toxic chemical c) an anti-inflammatory corticosteroid, fluticasone propionate (FL). Our suggest important synergistic effect on air-blood barrier sensitivity, cytotoxicity inflammation, when combined. best our knowledge, this is first time been described lung-on-chip technology. thus represents state-of-the-art pre-clinical study risks, drug safety efficacy.

Language: Английский

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