Evaluation of developmental toxicity of chlorpyrifos through new approach methodologies: a systematic review

Archives of Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Abstract Chlorpyrifos (CPF) is an organophosphorus pesticide of concern because many in vivo animal studies have demonstrated developmental toxicity exerted by this substance; however, despite its widespread use, evidence from epidemiological still limited. In study, we collected all the information generated twenty-first century on CPF using new approach methodologies. We critically evaluated and integrated coming 70 papers considering human, rodent, avian fish models. The comparison with available adverse outcome pathways allows us to conclude that outcomes observed animals, such as memory learning impairments well reduction cognitive function, could involve several mechanisms action including inhibition acetylcholinesterase, overactivation glutamate receptors activation mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, followed both disruption neurotransmitter release increase oxidative stress apoptosis.

Язык: Английский

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Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: Possible implications for SARS-CoV-2 impact on brain development

Reproductive Toxicology, Год журнала: 2022, Номер 111, С. 34 - 48

Опубликована: Май 5, 2022

Язык: Английский

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Molecular and Functional Characterization of Different BrainSphere Models for Use in Neurotoxicity Testing on Microelectrode Arrays

Cells, Год журнала: 2023, Номер 12(9), С. 1270 - 1270

Опубликована: Апрель 27, 2023

The currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low throughput hinder their application large numbers of chemicals. To overcome these limitations, in vitro are being developed based human-induced pluripotent stem cells (hiPSC) that allow higher at lower costs. We applied six different protocols to generate 3D BrainSphere models acute NT evaluation. These include three media 2D neural induction two subsequent differentiation resulting self-organized, organotypic neuron/astrocyte microtissues. All yielded nearly 100% NESTIN-positive hiPSC-derived progenitor (hiNPCs), though with gene expression profiles concerning regional patterning. Moreover, immunocytochemistry analyses revealed the choice determines patterns. On functional level, BrainSpheres exhibited levels electrical activity microelectrode arrays (MEA). Spike sorting allowed characterization mixed cultures consisting GABAergic, glutamatergic, dopaminergic, serotonergic, cholinergic neurons. A test method testing, human multi-neurotransmitter receptor (hMNR) assay, was proposed apply such MEA-based spike sorting. promising tools not only toxicology but also drug development disease modeling.

Язык: Английский

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Prediction of in vivo prenatal chlorpyrifos exposure leading to developmental neurotoxicity in humans based on in vitro toxicity data by quantitative in vitro–in vivo extrapolation

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Март 7, 2023

Introduction : Epidemiological studies in children suggested that utero exposure to chlorpyrifos (CPF), an organophosphate insecticide, may cause developmental neurotoxicity (DNT). We applied quantitative vitro – vivo extrapolation (QIVIVE) based on concentration and non-choline esterase-dependent effects data combined with Benchmark dose (BMD) modelling predict oral maternal CPF during pregnancy leading fetal brain effect concentration. By comparing the results from epidemiological studies, we evaluated contribution of endpoints mode action (MoA) for CPF-induced DNT. Methods: A maternal-fetal PBK model built PK-Sim ® was used perform QIVIVE predicting concentrations a pregnant women population at 15 weeks gestation cell lysate obtained human induced pluripotent stem cell-derived neural cells undergoing differentiation towards neurons glia exposed 14 days. The were BMD modelling. Results: upper converted into doses which ranged 3.21 271 mg/kg bw/day. Maternal blood levels reporting DNT findings their estimate using model. It 0.11 140 μg/kg Discussion: effective daily intake predicted several orders magnitude higher than exposures estimated induce non-cholinergic neurotoxic responses, captured by analyzed test battery. These also LOEC cholinergic effects. Therefore, predictive value investigated effects, although possibly relevant other chemicals, not adequately represent potential key events MoA CPF-associated

Язык: Английский

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Assessment of neurotransmitter release in human iPSC-derived neuronal/glial cells: a missing in vitro assay for regulatory developmental neurotoxicity testing

Reproductive Toxicology, Год журнала: 2023, Номер 117, С. 108358 - 108358

Опубликована: Фев. 28, 2023

Human induced pluripotent stem cell (hiPSC)-derived neural cells (NSCs) and their differentiated neuronal/glial derivatives have been recently considered suitable to assess in vitro developmental neurotoxicity (DNT) triggered by exposure environmental chemicals. The use of human-relevant test systems combined with assays specific for different neurodevelopmental events, enables a mechanistic understanding the possible impact chemicals on developing brain, avoiding extrapolation uncertainties associated vivo studies. Currently proposed battery regulatory DNT testing accounts several study key processes, including NSC proliferation apoptosis, differentiation into neurons glia, neuronal migration, synaptogenesis, network formation. However, measure interference compounds neurotransmitter release or clearance are at present not included, which represents clear gap biological applicability domain such battery. Here we applied HPLC-based methodology neurotransmitters previously characterized hiPSC-derived model undergoing towards glia. Glutamate was assessed control cultures upon depolarization, as well repeatedly exposed some known neurotoxicants (BDE47 lead) chemical mixtures. Obtained data indicate that these ability glutamate vesicular manner, both concur maintenance extracellular levels. In conclusion, analysis is sensitive readout should be included envisioned testing.

Язык: Английский

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Transcriptomic characterization of 2D and 3D human induced pluripotent stem cell-based in vitro models as New Approach Methodologies for developmental neurotoxicity testing

Toxicology, Год журнала: 2024, Номер 510, С. 154000 - 154000

Опубликована: Ноя. 17, 2024

Язык: Английский

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Quality criteria for in vitro human pluripotent stem cell-derived models of tissue-based cells

Reproductive Toxicology, Год журнала: 2022, Номер 112, С. 36 - 50

Опубликована: Июнь 11, 2022

Язык: Английский

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Molecular and functional characterization of different BrainSphere models for use in neurotoxicity testing on microelectrode arrays

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Март 13, 2023

Abstract The currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low throughput hinder their application large numbers of chemicals. To overcome these limitations, in vitro are developed which based human induced pluripotent stem cells (hiPSC) that allow higher at lower costs. We applied six different protocols to generate 3D BrainSphere models acute NT evaluation. These include three media 2D neural induction two subsequent differentiation resulting self-organized, organotypic neuron/astrocyte microtissues. All yielded nearly 100 % nestin-positive hiPSC-derived progenitor (hiNPCs) yet with gene expression profiles concerning regional patterning. Moreover, immunocytochemistry analyses revealed the choice determines patterns. On functional level, BrainSpheres exhibited levels electrical activity microelectrode arrays (MEA). Spike sorting allowed characterization mixed cultures consisting GABAergic, glutamatergic, dopaminergic, serotonergic, cholinergic neurons. A test method testing, multi-neurotransmitter receptor (hMNR) assay, was proposed applying such MEA-based spike sorting. not only promising tools toxicology but also drug development disease modeling.

Язык: Английский

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Human neural stem cells in developmental neurotoxicology: Current scenario and future prospects

Advances in neurotoxicology, Год журнала: 2023, Номер unknown, С. 197 - 237

Опубликована: Янв. 1, 2023

Язык: Английский

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