Citation:

Crofton, K., A. Bassan, M. Behl, Y. Chusak, E. Fritsche, J. Gearhart, M. Marty, M. Mumtaz, M. Pavan, P. Ruiz, T. Shafer, M. Sachana, R. Selvam, L. Stavitskaya, D. Szabo, S. Szabo, R. Tice, D. Wilson, D. Woolley, AND G. Myatt. Current status and future directions for a neurotoxicity hazard assessment framework that integrates in silico approaches. Computational Toxicology. Elsevier B.V., Amsterdam, Netherlands, 22:100223, (2022). https://doi.org/10.1016/j.comtox.2022.100223

Impact/Purpose:

This paper presents paradigms that describe the current state of knowledge for understanding the biological mechanisms underlying neurotoxicity and developmental neurotoxicity. Having a good understanding of these mechanisms is critical to applying New Approach Methodologies (NAMs) including in silico approaches to environmental decision-making. This will be of interest to EPA Program Offices that apply NAMs in their work, including TSCA, FIFRA and other environmental legislation.

Description:

Neurotoxicology is the study of adverse effects on the structure or function of the developing or mature adult nervous system following exposure to chemical, biological, or physical agents. The development of more informative alternative methods to assess developmental (DNT) and adult (NT) neurotoxicity induced by xenobiotics is critically needed. The use of such alternative methods including in silico approaches that predict DNT or NT from chemical structure (e.g., statistical-based and expert rule-based systems) is ideally based on a comprehensive understanding of the relevant biological mechanisms. This paper discusses known mechanisms alongside the current state of the art in DNT/NT testing. In silico approaches available today that support the assessment of neurotoxicity based on knowledge of chemical structure are reviewed, and a conceptual framework for the integration of in silico methods with experimental information is presented. Establishing this framework is essential for the development of protocols, namely standardized approaches, to ensure that assessments of NT and DNT based on chemical structures are generated in a transparent, consistent, and defendable manner.

URLs/Downloads:

Record Details: