Current Status and Future Directions for a Neurotoxicity Hazard Assessment Framework That Integrates Approaches

Overview

Journal Comput Toxicol

Specialty Biology

Date 2022 Jul 18

PMID 35844258

Authors

Kevin M Crofton

Arianna Bassan

Mamta Behl

Yaroslav G Chushak

Ellen Fritsche

Jeffery M Gearhart

Mary Sue Marty

Moiz Mumtaz

Manuela Pavan

Patricia Ruiz

Magdalini Sachana

Rajamani Selvam

Timothy J Shafer

Lidiya Stavitskaya

David T Szabo

Steven T Szabo

Raymond R Tice

Dan Wilson

David Woolley

Glenn J Myatt

Affiliations

Soon will be listed here.

Abstract

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 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. 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 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.

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