Caenorhabditis elegans Neurotoxicity Testing: Novel Applications in the Adverse Outcome Pathway Framework

Abstract

Neurological hazard assessment of industrial and pesticidal chemicals demands a substantial amount of time and resources. <i>Caenorhabditis elegans</i> is an established model organism in developmental biology and neuroscience. It presents an ideal test system with relatively fewer neurons (302 in hermaphrodites) versus higher-order species, a transparent body, short lifespan, making it easier to perform neurotoxic assessment in a time and cost-effective manner. Yet, no regulatory testing guidelines have been developed for <i>C. elegans</i> in the field of developmental and adult neurotoxicity. Here, we describe a set of morphological and behavioral assessment protocols to examine neurotoxicity in <i>C. elegans</i> with relevance to cholinergic and dopaminergic systems. We discuss the homology of human genes and associated proteins in these two signaling pathways and evaluate the morphological and behavioral endpoints of <i>C. elegans</i> in the context of published adverse outcome pathways of neurodegenerative diseases. We conclude that <i>C. elegans</i> neurotoxicity testing will not only be instrumental to eliminating mammalian testing in neurological hazard assessment but also lead to new knowledge and mechanistic validation in the adverse outcome pathway framework.