EQUIPOTENTIAL SUBNARCOTIC CONCENTRATIONS OF SOLVENTS IN AIR, IN BLOOD, AND AT THE TARGET STRUCTURE

Airborne concentrations evoking the same inhibition of seizure dischar ge generation and maintenance were determined in rats and mice after a single inhalatory exposure to five aromatic non-polar narcotic compou nds (benzene, toluene, o-xylene, ethylbenzene and styrene), two more p olar chlorinated solvents (chloroform, methylene chloride), and aceton e as a representative of polar, hydrophilic narcotic substances. The s olvent blood and brain concentrations corresponding to these isoeffect ive air concentrations were determined using gas chromatography (Tab.2 ). Concentrations at the site of action were computed assuming various proportions of lipidic and aqueous components of the ( hypothetical) target structure: at a lipo/hydrophilicity ratio of 54.5/45.5 the esti mated concentrations had the lowest inter-substance variability (Fig.1 ) which was by two orders lower than that of isoeffective blood levels (Fig.2). Both the only 60% share of lipids on the efficacy coefficien t and the low molecular ratio of solvent to lipid molecules (less than 1:400) testify against the primary and exclusive lipotropic mechanism of solvent induced subnarcotic states and narcosis.