Self-organizing human neuronal cultures in the modeling of environmental impacts on learning and intelligence DOI
Thomas Härtung,

Jack R. Thornton,

Lena Smirnova

et al.

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

New Approach Methodologies for Developmental Neurotoxicity Testing: Understanding How the Underlying Biology and Assay Characteristics Build Confidence in Using Data to Support Regulatory Decisions DOI
S. Boyd,

Kelly E Carstens,

Anna Lowit

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Transcriptomic characterization of 2D and 3D human induced pluripotent stem cell-based in vitro models as New Approach Methodologies for developmental neurotoxicity testing DOI

Malene Lislien,

Eliška Kuchovská, Julia Kapr

et al.

Toxicology, Journal Year: 2024, Volume and Issue: 510, P. 154000 - 154000

Published: Nov. 17, 2024

Language: Английский

Citations

2
Brain organoids as a translational model of human developmental neurotoxicity DOI
Thomas Härtung, Maren Schenke, Lena Smirnova

et al.

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 83 - 106

Published: Jan. 1, 2024

Language: Английский

Citations

1
Inhibition of Neural Crest Cell Migration by Strobilurin Fungicides and Other Mitochondrial Toxicants DOI Creative Commons

Viktoria Magel,

Jonathan Blum,

Xenia Dolde

et al.

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
Developmental neurotoxicity evaluation of acrylamide based on in vitro to in vivo extrapolation by pregnancy PBTK modelling DOI Creative Commons
Ylva Johansson,

Roseline Awoga,

Anna Forsby

et al.

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

0
Developmental Neurotoxicology From Regulatory Testing Perspective: History, Achievements and Challenges DOI
Yifei Wang,

Antonia Egert,

Maren Schenke

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
Self-organizing human neuronal cultures in the modeling of environmental impacts on learning and intelligence DOI
Thomas Härtung,

Jack R. Thornton,

Lena Smirnova

et al.

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0