Relative Acute Neurotoxicity of Solvents: Isoeffective Air Concentrations of 48 Compounds Evaluated in Rats and Mice

Effect-air concentration regressions of 48 common solvents (aromatic, aliphatic, and chlorinated hydrocarbons, alcohols, ketones, acetates) were determined for 4-hr inhalation exposures in male rats and for 2-hr exposures in female mice. Inhibition of propagation and maintenance of the electrically evoked seizure discharge was used as a criterion of the acute neurotropic effect. The isoeffective concentrations in air were estimated by interpolation on the level of one-third of the maximum effect (ECC). ECC estimates ranged from 90 to 24,000 ppm and were several times lower than concentrations evoking behavioral inhibition and by one to two orders lower than concentrations inducing narcosis. Correlations between corresponding values in both species were high (r > 0.9), indicating a relative independence of the estimates from experimental conditions. The relative potency estimates had only negligible correlation with octanol:water distribution coefficients or other physicochemical predictors for the whole sample of solvents, but moderate to high correlation (r = 0.5 to 0.9) in homogenous groups of nonpolar solvents, permitting cautious predictions. When applied to known effective concentrations of some solvents on human performance and subjective state, the comparative potency procedure suggests that ceiling and STEL values of some solvents may not reliably protect workers from acute nervous depression.