Superfund Research Program
Human Dosimetry for Assessment of Exposure to Volatile Compounds
Project Leader: Michael S. Morgan
Grant Number: P42ES004696
Funding Period: 1995 - 2006
Final Progress Reports
Year: 2005 1999
Dr. Morgan and his team of investigators recently completed an experimental study of the influence of ethanol on the ability of humans to eliminate industrial solvents taken in by inhalation. Ten human volunteers were exposed via inhalation on two separate occasions to low levels of the solvent 1,1,1-trichloroethane. One of these exposures occurred after each subject was given known doses of ethanol (by ingestion) over a specific period of time. Prior to the other solvent exposure, subjects were given no ethanol. The parent compound and the products of its metabolism were analyzed from breath, blood, and urine samples taken during and after both exposures. From this data, the difference in metabolic rates in subjects with and without prior ethanol consumption was assessed. The results showed that ethanol increased the rate of metabolism of the solvent by a mean of 27%, with no difference found between male and female subjects.
The influence of ethanol is accurately predicted by a mathematical model that uses realistic input values from each of the subjects, and it can therefore be accounted for in evaluating workplace exposures. Only two other studies of this type have been conducted in human volunteers, with results that differ from the project’s in important ways. The most important difference is that the project researchers’ study used a solvent that is normally biotransformed to a very limited extent, while the other studies used solvent that undergo extensive biotransformation even in subjects not given ethanol. In the latter studies little or no enhancement by ethanol was found. Mathematical modeling can also be used to explain the difference between the researcher’s study and prior work.
Currently project researchers are engaged in a field application of the dosimetric principles that have been established in their laboratory experiments. Painters at cabinet manufacturing facilities in the area who are exposed to volatile organic compounds at work have agreed to provide breath samples during and after work, together with integrated air samples taken from the breathing zone. Project researchers’ hypothesis is that breath concentrations will be correlated with air concentrations, but with important physiologic factors modifying that correlation. The researcher’s previous mathematical model will be used to predict the air-breath relationship, and this will be compared to observations. At present they have enrolled twelve workers in the study, and plan to recruit another ten to fifteen from similar workplaces.