Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Language: Английский
Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
0
Toxicologic Pathology, Journal Year: 2025, Volume and Issue: unknown
Published: May 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.
Language: Английский
Citations
0
NeuroToxicology, Journal Year: 2025, Volume and Issue: unknown
Published: May 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.
Language: Английский
Citations
0
Toxicologic Pathology, Journal Year: 2025, Volume and Issue: unknown
Published: May 31, 2025
The 21st ESTP’s (European Society of Toxicology Pathology) Annual Congress (2024) included a 3-hour scientific session on developmental neurotoxicity (DNT) as applied to chemical safety assessments. Key concepts this were provide an introduction public concerns around endpoint, status update practical aspects DNT studies, insights into the use studies within regulatory context, well some pointers how evaluate specific parameters. Understanding biological and technical variability in performing neuropathology examinations (such morphometric evaluation) is critical during course evaluation. Using thyroid hormone disruption example, challenges pitfalls impacting data interpretation discussed. Results from European Centre for Ecotoxicology Chemicals (ECETOC) Thyroid Task Force regarding hormone–related neurodevelopmental toxicity humans rodents presented. Histopathological findings brain potential changes cochlea pups associated with imbalance dams pregnancy shown. A case presentation Extended One-Generation Reproductive Toxicity Study (EOGRTS) showing histopathological absence endpoints was included. In conclusion, all participants underscored need integrated evaluation risk assessment.
Language: Английский
Citations
0
Toxicology, Journal Year: 2024, Volume and Issue: 510, P. 154000 - 154000
Published: Nov. 17, 2024
Language: Английский
Citations
2
Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 83 - 106
Published: Jan. 1, 2024
Language: Английский
Citations
1
Toxicology, Journal Year: 2024, Volume and Issue: unknown, P. 153950 - 153950
Published: Sept. 1, 2024
Acrylamide (ACR) is a known neurotoxicant that can pass the placenta and has been detected in breast milk. Some vivo vitro studies indicate ACR exposure might lead to developmental neurotoxicity (DNT). Here, we have developed physiologically-based toxicokinetic model for pregnant human population using PK-Sim. We performed an extrapolation (IVIVE) of data collected from neuroblastoma SH-SY5Y cells exposed during differentiation ACR. The PBTK was successfully evaluated predicted fetal plasma concentrations low nM range after exposing estimated average daily intake women. IVIVE showed (fM-nM) induced attenuated neuronal cell model, were relevant oral intake. However, doses µM range, found be unrealistic by through food case due environmental pollution or occupational exposure, these may reached plasma. findings this study raise concern regarding pregnancy as well relevance testing are several orders magnitude higher than concentrations.
Language: Английский
Citations
1
Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2057 - 2057
Published: Dec. 12, 2024
Cell-based test methods with a phenotypic readout are frequently used for toxicity screening. However, guidance on how to validate the hits and integrate this information other data purposes of risk assessment is missing. We present here such procedure exemplify it case study neural crest cell (NCC)-based developmental picoxystrobin. A library potential environmental toxicants was screened in UKN2 assay, which simultaneously measures migration cytotoxicity NCC. Several strobilurin fungicides, known as inhibitors mitochondrial respiratory chain complex III, emerged specific hits. From these, picoxystrobin chosen roadmap leading from cell-based testing towards toxicological predictions. Following stringent confirmatory testing, an adverse outcome pathway developed provide testable hypothesis. Mechanistic studies showed that oxygen consumption rate inhibited at sub-µM concentrations after 24 h pre-exposure. Migration 100 nM range, under assay conditions forcing cells rely mitochondria. Biokinetic modeling predict intracellular concentrations. Assuming oral intake picoxystrobin, consistent acceptable daily level, physiologically based kinetic suggested brain 0.1–1 µM may be reached. Using broad array hazard toxicokinetics data, we calculated margin exposure ≥ 80 between lowest vitro point departure highest predicted tissue concentration. Thus, our exemplifies hit follow-up strategy contributes paving way next-generation assessment.
Language: Английский
Citations
1
Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Language: Английский
Citations
0
Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Language: Английский
Citations
0