Acute interactive pharmacologic effects of inhaled toluene and dichloromethane on rat brain electrophysiology

Abstract

Toluene (TOL) and dichloromethane (DCM) are widely used industrial solvents and are common components of solvent mixtures that are voluntarily inhaled to produce altered states of consciousness. In previous studies we characterized some of the acute electrophysiologic effects of these solvents. Opposite effects were noted for some measures, suggesting that they might be antagonistic when combined. In this study we examined the solvents again singly (10,700 and 16,000 ppm) and also in combination (16,000 ppm: 33/67 and 67/33% TOL/DCM ratios). The single gases caused effects similar to those observed previously. Combined effects varied, dependent upon the particular variable examined and the major gas in the mixture. In some respects the solvents were concordant, exerting similar effects on a variable, e.g., both solvents prolonged the latencies of components of the brainstem auditory-evoked response. In other respects they were discordant, e.g., whereas toluene caused mean EEG frequency to increase, dichloromethane had the opposite effect. Sometimes the solvents had similar effects alone, but acted independently in combination. Nonindependent interactions were also observed-both additive/subtractive or positively or negatively synergistic. The results further demonstrate and emphasize the unique patterns of acute central nervous system effects that can be effected by solvents that might have a common behavioral endpoint such as anesthesia, and the results characterize a variety of electrophysiologic interactions between these two solvents. Although there were several variables exhibiting synergistic relationships, independent or additive interactions were the most common.