Chapter 22 - In Vitro Models for Testing Organophosphate-Induced Neurotoxicity and Remediation

Abstract

The chapter discusses and compares the toxic effects of various types of organophosphate (OP) neurotoxicants on cell and tissue culture models (i.e., in vitro models), that represent the constituents of the central nervous system (CNS). Like several environmental neurotoxicants, OP compounds affect multiple cell types, employ various mechanisms of toxic action, produce sublethal functional impairment to cells at low concentrations, and are nonessential from a primary metabolic standpoint. Individual cells are the basic functional unit in which the toxic actions of chemicals can be deduced, and cell and tissue culture models excel at providing controlled environments for exposing known cell types to toxicants and directly measuring their biological effects. This chapter summarizes existing studies on OP-induced neurotoxicity in vitro and critically evaluates the strengths, weaknesses, and further opportunities offered by such studies. A brief overview of concepts of in vitro neurotoxicology is presented, followed by analysis of neuronal and glial effects of OP compounds in vitro that may be related to neurotoxicity, such as esterase inhibition, neurite extension, and several additional biochemical end points. The novel use of cell cultures to test for enzymatic remediation of OP neurotoxicity is described as a new area for investigation. Recommendations for future studies that would increase the value of in vitro studies are also proposed. Information generated from in vitro studies is beginning to yield an improved understanding of the effects of OP compounds on neuronal and glial cells.