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Solvents, Ethanol, Car Crashes & Tolerance

How risky is inhalation of organic solvents?

Philip J. Bushnell

Modeling Solvent Vapor Effects

A research program in the National Health and Environmental Effects Research Laboratory of the U.S. Environmental Protection Agency has led to some surprising considerations regarding the potential hazard of exposure to low concentrations of solvent vapors. This program involved conducting experiments to characterize the acute behavioral and neurophysiological effects of inhaling these vapors, developing computational models to understand the relation between the concentration of the vapor in the inhaled air and in critical tissues of the body, and carrying out meta-analyses of the relations between internal doses and various effects in rats and in humans. This experimental work demonstrated that inhaling solvent vapors causes robust changes in cognitive, sensory and motor function in rats; the concentration of the solvent in the brain at the time of functional measurement accurately predicts the magnitude of the effect; and computational models can accurately estimate the concentration of the solvent in the brain and blood under a variety of exposure scenarios. Meta-analyses of dose-effect relations in rats and in humans showed that the potency of the solvent depends greatly on the consequences associated with responding in the test, but, given similar incentives, rats and humans do not differ in their sensitivity to the four solvents tested.

Ethanol, the alcohol that is commonly consumed in a variety of drinks, is chemically an organic solvent and affects the CNS in ways that are very similar to the effects of other inhaled solvents. Because the effects of ethanol and some solvents have been measured using the same test methods, it is possible to relate the potency of solvents and ethanol quantitatively. We applied this relation, called a dose-equivalence equation, to the extensive database relating ingestion of ethanol to fatal automobile crashes. Surprisingly, this analysis revealed that acute exposure to solvent vapors at concentrations below those associated with long-term effects appears to increase the risk of a fatal automobile accident. Furthermore, this increase in risk is comparable to the risk of death from leukemia after long-term exposure to benzene, another solvent, which has the well-known property of causing this type of cancer.

However, other experiments have revealed also that rats can become tolerant to these “acute” effects of solvents—in some situations completely overcoming impairment that is initially caused by inhaling high concentrations of the chemical. After exploring several aspects of this tolerance, it became apparent that assessment of the risk of acute exposure to solvents is not simply a balance between toxicity and tolerance. As will be discussed below, it depends on value judgments and the perception of the risks and benefits associated with normal behavior. The best we can do under these circumstances is to pose the difficult questions about the degree to which the risk of acute exposure can be ameliorated by tolerance.

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