Research Brief 65
Superfund Research Program
Toxicokinetics of Volatile Organic Compounds
Volatile organic compounds are among the most commonly found contaminants at Superfund sites. Some of the more recognized compounds in this group are benzene and toluene, which happen to be components of gasoline and other fuels. Not surprisingly, these and other volatile organic compounds are common pollutants around fuel spills and leaking underground storage tanks, from where they can migrate into groundwater and, subsequently, drinking water supplies.
Human contact with these compounds is not just limited to exposures arising from hazardous waste sites and the fuels we use for transportation. The widespread use of volatile organic compounds in many commonly used products such as paints, glues and lacquers, combined with the volatility of these substances, makes them ubiquitous air pollutants. As a result, low level exposure to volatile organic compounds is a reality for the general population. Certain populations, including people who work in or live near industries that make or use volatile organic compounds, are exposed to higher than average levels of these substances.
The widespread presence of volatile organic compounds in environmental and occupational settings leads to the likelihood that individuals and groups who might be exposed to such compounds released from a Superfund site or other pollution source will also be exposed from general environmental sources and use of consumer products. It is often useful to characterize total exposures (i.e. from many routes and many sources) in order to better understand the significance of a particular pollution source, and biomarkers of exposure such as levels of solvent in breath or blood can be a useful tool to do this.
However, the relationship between total exposures and blood or breath levels can be a complex one and include modifying factors that vary from person to person. This variability is also a concern because people vary widely in their ability to process these compounds. Some individuals clear volatile organic compounds from the body rather quickly, while others process these compounds slowly, leading to a longer half-life in the body. These differences in eliminating volatile organic compounds from the body can make some individuals more susceptible to adverse health effects. Even though it is apparent that toxicant clearance and effects are greatly influenced by factors specific to an individual, scientists do not completely understand the reasons underlying these differences.
To improve understanding in this area, researchers at the University of Washington have been investigating the "toxicokinetics" of volatile organic compounds. In these studies, the researchers have made significant advances towards understanding factors that contribute to individual differences in the uptake, distribution and clearance of toluene, a representative volatile organic compound, in the human body.
Toxicokinetics is essentially the study of how substances get into and out of the body, including what happens to them when inside the body. It involves understanding how toxicants are absorbed, distributed, metabolized and excreted from the body. Toxicokinetic studies are especially helpful for resolving the intricate relationships between exposure, time-varying levels of toxicants in body tissues, and adverse health effects.
Early studies by the University of Washington researchers showed that a person's breathing rate, age, body weight, amount of fat tissue, and blood/air partition coefficient all affect the absorption, distribution and elimination of toluene in people. More recent findings suggest that women's individual toxicokinetics differ from men's in physiologically-predictable ways. These latter studies showed that the clearance of toluene is significantly greater for men than women under both resting and exercising conditions. These results are most likely explained by the relatively higher levels of adipose tissue in women, indicating the amount of body fat is an important consideration in assessing potential adverse health effects from exposures to volatile organic compounds.
These findings were obtained from studies in which volunteers inhaled low levels of dueterated toluene, a stable isotope form of toluene that allows for easy tracking of the administered dose and gives a means to separate the controlled exposure from background exposures to toluene. Toluene was measured in blood and breath samples that were collected before, during and after exposure. In addition, metabolites of toluene were measured in urine. These biological indicators of toluene exposure were used to describe the time course of chemical disposition in the body. Comparing this toxicokinetic information to many person-specific factors, such as age and body weight, helped the researchers identify physiological attributes that influence individual toluene toxicokinetics.
In addition to revealing what physiological factors influence the uptake, distribution and clearance of toluene in the body, these studies showed that toluene levels in the breath are an accurate and noninvasive indicator of the absorbed dose. Moreover, these studies have supported the development and validation of a physiologically based toxicokinetic model (PBTK) for toluene. The PBTK model is so advanced that it is now possible to estimate both the amount of absorbed toluene in the body and the external concentration of toluene in the air from the amount measured in breath samples.
Current studies include an investigation of the effects of smoking on toluene toxicokinetics and field studies of ambient and breath concentrations of toluene and other volatile organic compounds in workers and residents with above average exposures. The latter studies will help test the applicability of the PBTK model to real-life settings.
By improving our understanding of the factors underlying individual differences in toluene toxicokinetics, this research is improving human health risk assessment for toluene and, potentially, other volatile organic compounds. These efforts are also leading to better predictive models and improved biomarker-based exposure assessment for individuals who are exposed to these ubiquitous environmental pollutants.
For More Information Contact:
David A Kalman
Department of Environmental and Occupational Health Sciences
Health Sciences Building, F-463
Seattle, WA 98195-7234
To learn more about this research, please refer to the following sources:
- Pierce CH. 1999. A comparison of 1H8- and 2H8-toluene toxicokinetics in humans. Xenobiotica 29(1):93-108.
- Vicini P, Pierce CH, Dills RL, Morgan MS, Kalman DA. 1999. Individual prior information in a physiological model of 2H8-toluene kinetics: an empirical Bayes estimation strategy. Risk Anal 19(6):1127-1134. PMID:10765452
- Pierce CH, Dills RL, Morgan MS, Vicini P, Kalman DA. 1998. Biological Monitoring of controlled toluene exposure. Int Arch Occup Environ Health 71:433-444. PMID:9826075
- Pierce CH, Dills RL, Lewandowski TA, Morgan MS, Wessels MA, Shen D, Kalman DA. 1997. Estimation of background exposure to toluene using a physiologically-based kinetic model. J Occup Health 39(2):130-137.
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