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Solvents, Ethanol, Car Crashes and Tolerance: How Risky is Inhalation of Organic Solvents?
Bushnell, P. Solvents, Ethanol, Car Crashes and Tolerance: How Risky is Inhalation of Organic Solvents? American Scientist. Sigma Xi, The Scientific Research Society, New Haven, CT, (4):282-291, (2013).
This report assembles several decades of research by NHEERL scientists into the immediate effects of inhaled organic solvents into a story that links experimental work with rodents to the potential public health impacts of acute, low-level solvent inhalation. Through quantitative meta-analysis of the effects of solvents and ethanol on human and animal reaction time, this work reveals a substantial risk of a fatal automobile crash after inhaling toluene at concentrations below its RfC, Cumulated over a 30-year period, this risk is equivalent to the 30-year cumulative risk of developing leukemia from occupational exposure to benzene. The paper concludes by discussing various forms of metabolic and behavioral tolerance as factors mitigating this risk.
A research program in the National Health and Environmental Effects Research Laboratory of the U.S. EPA 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 relationship between the concentrations of the vapor in the inhaled air and in critical tissues of the body, and carrying out meta-analyses of the relationships 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 chemical 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 relationships in rats and in humans showed that the potency of the solvent depends greatly upon 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 that were tested. Ethanol, the alcohol that is commonly consumed in a variety drinks, is chemically an organic solvent, and affects the CNS in ways that are very similar to the effects of other inhaled solvents. Because effects of ethanol and some solvents have been measured using the same test methods, it is possible to relate the potency of these solvents and ethanol quantitatively. We applied this relationship, called a dose-equivalence equation (Benignus et al., 2007), to the extensive database relating ingested 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 that 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 upon 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 difficult questions about the degree to which the risk of acute exposure can be ameliorated by tolerance.