Neurotoxicological hazard assessment with a human cell-based battery
October 2022
IUF - Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany(1)
University of Konstanz, Konstanz, Germany(2)
University of Konstanz, Konstanz, Germany(2)
Developmental neurotoxicity (DNT) is a major safety concern for all chemicals of the human exposome. Therefore test methods with high throughput and human relevance are urgently needed. Here the feasibility of DNT hazard assessment based on new approach methods (NAMs) was explored. An in vitro battery (IVB) was assembled from ten individual NAMs to probe the effects of chemicals on various fundamental neurodevelopmental processes. All assays used human neural cells at different developmental stages. This allowed the assessment of disturbances of (i) proliferation of neural progenitor cells (NPC); (ii) migration of neural crest cells, radial glia cells, neurons and oligodendrocytes; (iii) differentiation of NPC into neurons and oligodendrocytes; and (iv) neurite outgrowth of peripheral and central neurons. In parallel, cytotoxicity measurements were obtained. The feasibility of concentration-dependent screening and of reliable biostatistical processing of the complex multi-dimensional data was explored with a set of 120 test compounds, containing subsets of pre-defined positive and negative DNT compounds. The battery provided alerts (hit or borderline) for 24 of 28 known toxicants (82% sensitivity), and for none of the 17 negative controls. Based on the results from this screen project, strategies were developed on how IVB data may be used in the context of risk assessment scenarios employing integrated approaches for testing and assessment (IATA).
Establishment of a human cell-based in vitro battery to assess developmental neurotoxicity hazard of chemicals
Ellen Fritsche(1), Jonathan Blum(2), Marcel Leist(2)
Added on: 12-02-2022
[1] https://www.sciencedirect.com/science/article/pii/S0045653522035287?via%3Dihub[2] https://www.uni-konstanz.de/en/university/news-and-media/current-announcements/press-releases/press-releases-in-detail/neurotoxikologische-gefahrenbewertung-ohne-tierversuche/
