The Neurotoxicity of Organic Solvents,Studied with in Vitro Models

The present paper deals with the general anaesthetic effect of organic solvents. The emphasis is on cell membranes as models for predicting the adverse reactions of the human nervous system to organic solvents, and for studying the mechanisms of their anaesthetic action. Human and rat erythrocyte and platelet membranes, rat synaptosomal membranes and cultured neural cell membranes were exposed in vitro to various concentrations (3–30mM) of benzene, toluene, o-xylene and styrene in the incubation mixtures. After exposure to a solvent for 30 minutes, the membrane integral protein integrity was determined by measuring ATPase and acetylcholinesterase activities. All measurements were performed in triplicate from 3 or 4 independent experiments with each exposure of solvent and each membrane isolation. The enzyme inhibition was dose-dependent, and differed after solvent treatment in all membrane preparations tested in increasing order, as follows: benzene, toluene, styrene, o-xylene. The results support the protein theories on the mechanism of the anaesthetic action of various industrial organic solvents. The integral membrane proteins contain hydrophobic pockets which may bind anaesthetics, e.g. solvents which change the properties of integral enzymes. The effects of solvents in peripheral models are quite similar to those in neural membranes in vitro. Therefore, these membrane models can serve as test models when the narcotic potencies of the solvents are being evaluated, or at least for screening purposes and for studies of the mechanisms of solvent neurotoxicity.