ROUTE-TO-ROUTE EXTRAPOLATION OF THE TOXIC POTENCY OF MTBE

MTBE is a volatile organic compound used as an oxygenating agent in ga soline. Inhalation from fumes while refueling automobiles is the princ iple route of exposure for humans, and toxicity by this route has been well studied. Oral exposures to MTBE exist as well, primarily due to groundwater contamination from leaking stationary sources, such as und erground storage tanks. Assessing the potential public health impacts of oral exposures to MTBE is problematic because drinking water studie s do not exist for MTBE, and the few oil-gavage studies from which a r isk assessment could be derived are limited This paper evaluates the s uitability of the MTBE database for conducting an inhalation route-to- oral route extrapolation of toxicity. This includes evaluating the sim ilarity of critical effect between these two routes, quantifiable diff erences in absorption, distribution, metabolism, and excretion, and su fficiency of toxicity data by the inhalation route. We conclude that s uch an extrapolation is appropriate and have validated the extrapolati on by finding comparable toxicity between a subchronic gavage oral bio assay and oral doses we extrapolate from a subchronic inhalation bioas say. Our results are extended to the 2-year inhalation toxicity study by Chun et al. (1992) in which rats were exposed to 0, 400, 3000, or 8 000 ppm MTBE for 6 hr/d, 5 d/wk. We have estimated the equivalent oral doses to be 0, 130, 940, or 2700 mg/kg/d. These equivalent doses may be useful in conducting noncancer and cancer risk assessments.