Elsevier eBooks, Год журнала: 2024, Номер unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Current Opinion in Toxicology, Год журнала: 2025, Номер unknown, С. 100528 - 100528
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
1
Frontiers in Toxicology, Год журнала: 2025, Номер 6
Опубликована: Янв. 10, 2025
Primary cell cultures from rodent brain are widely used to investigate molecular and cellular mechanisms of neurotoxicity. To date, however, it has been challenging reliably culture endogenous microglia in dissociated mixed cultures. This is a significant limitation most vitro neural models given the growing awareness importance interactions between neurons, astrocytes defining responses neurotoxic exposures. We recently developed tri-culture model consisting developing rat neocortex demonstrated that this more faithfully mimics vivo neuroinflammatory then standard neuron-only or neuron-astrocyte co-cultures. Here, we describe our protocol for generating tri-cultures cortical which all 3 types can be maintained up 1 month at same relative ratio observed neocortex. also discuss applications neurotoxicity testing, as well potential fill current gap assessing neuroinflammation testing battery developmental
Язык: Английский
Процитировано
0
Current Opinion in Toxicology, Год журнала: 2025, Номер unknown, С. 100517 - 100517
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
iScience, Год журнала: 2025, Номер 28(3), С. 112056 - 112056
Опубликована: Фев. 18, 2025
Язык: Английский
Процитировано
0
Environmental Science & Technology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 27, 2025
Zebrafish have emerged as a central model organism in toxicological research. embryos are exempt from certain animal testing regulations, which facilitates their use testing. Next to the zebrafish embryo acute toxicity test (ZFET) according OECD TG 236, fish used mechanistic investigations, chemical screenings, ecotoxicology, and drug development. However, inconsistencies applied protocols monitored endpoints addition lack of standardized data formats impede comprehensive meta-analyses cross-study comparisons. To address these challenges, we developed Integrated Effect Database for Toxicological Observations (INTOB), management tool that standardizes collection metadata phenotypic observations using controlled vocabulary. By incorporating more than 600 experiments into database subsequent analyses, demonstrate its utility improving comparability interoperability data. Our results show ZFET can detect spanning 7 orders magnitude at scale effect concentrations. We also highlight potential read-across analyses based on morphological fingerprints connection modes action, provide information control variability ZFET, importance time understanding exposure-effect assessments. full Findable, Accessible, Interoperable, Reusable (FAIR) set well analysis workflow how professional management, enabled with INTOB, marks significant advancement by offering framework systematic data, thus paving way reliable, data-driven risk assessment.
Язык: Английский
Процитировано
0
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Год журнала: 2025, Номер unknown, С. 503867 - 503867
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Toxicology, Год журнала: 2025, Номер 515, С. 154168 - 154168
Опубликована: Май 1, 2025
Exposure to organophosphate flame retardants (OPFRs) and phthalates is associated with neurodevelopmental deficits, impaired neuronal proliferation differentiation, altered neurotransmitter levels, learning memory. Here, we assessed the effects of acute chronic exposure OPFR triphenyl phosphate (TPhP) several on activity network development in male female rat primary cortical cultures grown micro-electrode arrays. Acute TPhP, diethyl phthalate (DEP), dibutyl (DBP), benzyl butyl (BBzP) inhibited activity, while TPhP DEP induced a hyperexcitation. Chronic DBP, BBzP, bis(2-ethylhexyl) (DEHP), its metabolite mono-2-ethylhexyl (MEHP) development. BBzP DEHP affected function at human-relevant concentrations as low 1 µM. metabolites DEP, had only limited effects. Although underlying mechanisms remain be elucidated, analysis endocrine mechanisms, including retinoic acid, X, liver prostaglandin E2 receptor, suggested that were not endocrine-mediated. Further research needed elucidate different responses exposure. Taken together, these results add evidence various illicit neurotoxic effects, some concentrations. These novel should considered risk assessment chemicals.
Язык: Английский
Процитировано
0
NeuroToxicology, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
There is a lack of confidence in the relevance zebrafish-based behavior data for chemical risk assessment. We extended an automated Visual and Acoustic Motor Response (VAMR) new approach method (NAM) 5-day post-fertilization (dpf) zebrafish to include 26, behavior-based endpoints that measure visual-motor responses, visual acoustic startle habituation learning, memory retention. A correlation analysis from 5,159 control larvae revealed more complex learning- memory-related yielded unique patterns. To build VAMR NAM, we established neuroactivity fingerprints using concentration-response profiles derived 63 reference chemicals targeting neurotransmission, neurodevelopmental signaling, or toxicologically-relevant pathways. Hierarchical clustering diverse toxicity fingerprints. Compounds targeted N-Methyl-D-aspartic acid (NMDA) gamma-aminobutyric type (GABAA) receptors reduced learning. Pathway modulators peroxisome proliferator-activated receptor delta (PPARδ) gamma (PPARγ), GABAA, dopamine, ryanodine, aryl hydrocarbon (AhR), G-protein-coupled tyrosine kinase SRC inappropriately accelerated Reference NMDA, PPARα, PPARδ, epidermal growth factor, bone morphogenetic protein, AhR, retinoid X, α2-adreno triggered inappropriate hyperactivity. Exposure GABAA antagonists elicited paradoxical excitation characterized by dark-phase sedation increased responses while exposure GABAA/B agonists altered same with opposite directionality. Relative chemicals, environmental known be GABA (Lindane, Dieldrine) (Tetrabromobisphenol (TBBPA)) predicted When paired phenotypically rich are powerful identify neuroactive chemicals.
Язык: Английский
Процитировано
0
Toxicologic Pathology, Год журнала: 2025, Номер unknown
Опубликована: Май 15, 2025
The International Academy of Toxicologic Pathology (IATP) Satellite Symposium on “New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives,” organized in Spain, addressed the growing need improved assessment neurotoxicity. Traditional neurotoxicity using vivo animal studies are impractical testing substantial number environmental chemicals that currently lack data early detection neuro-related adverse reactions drug discovery. NAMs, including human vitro assays small model organisms, have been developed faster cost-effective neurotoxic potential. While NAMs offer practicality, utility, valuable mechanistic insights, their integration into regulatory decision-making requires robust scientific validation technical characterization. Confidence application can be supported by mapping cellular outcomes to neuropathological findings mammals, humans, through Adverse Outcome Pathway (AOP) framework, Integrated Testing (IATA). Case presented demonstrated chemical safety evaluations, focusing developmental (DNT), Parkinson’s disease, drug-induced seizures. In conjunction with toxicology studies, represent a significant step toward advancing toxicity via hazard identification screening assessments.
Язык: Английский
Процитировано
0
NeuroToxicology, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
With the societal interest to decrease experimental animal testing for regulatory purposes, need reliable new approach methods (NAMs) has become evident. To ensure continued safe use of chemicals, NAMs should perform ideally at a comparable or better level sensitivity and specificity as in vivo modalities that they aim replace, especially if are be used hazard assessment. The relevant reference substances, selected with transparent criteria, forms cornerstone developing silico vitro NAMs. Claims on based results generated chemicals were previously scrutinised by independent expert panels whether substance hazardous property. CLP (Regulation (EC) No 1272/2008 classification, labelling packaging substances mixtures) key pillar EU management. evaluation all available information Committee Risk Assessment (RAC) their comparison classification criteria creates opportunity objectively compile lists positive substances. We collated list neurotoxic aid development neurotoxicity screened Annex VI reflected existing mode action data. identified included industrial active plant protection biocidal products. This neurotoxicants is not an exhaustive consensus list, which would result combining this those other authorities groups.
Язык: Английский
Процитировано
0