Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety

Botanicals are widely consumed as dietary supplements, medicines, and consumer products. Their chemical complexity and variability present challenges in safety assessment, including potential neurotoxicity. The Botanical Safety Consortium (BSC)‘s Neurotoxicity Working Group is exploring new approach methodologies (NAMs) for the screening of botanical extracts for neurotoxic effects. Areas covered: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and Caenorhabditis elegans. These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and C. elegans assays evaluate neurobehavioral responses. The paper also provides an account of the selection of botanical case studies based on expert judgment and existing neuroactivity/toxicity information. The proposed battery of assays will be tested with these case studies to evaluate their utility for neurotoxicity screening. Expert opinion: The complexity of botanicals necessitates the use of multiple NAMs for effective neurotoxicity screening. This paper discusses the evaluation of methodologies to develop a robust framework for evaluating botanical safety, including complex neuronal models and key neurodevelopmental process assays. It aims to establish a comprehensive screening framework.