Extrapolation of the Benzene Inhalation Unit Risk Estimate to the Oral Route of Exposure

A simple method for extrapolation of benzene-induced cancer risk from the inhalation to oral route is proposed. The method is based on the relative efficiency of benzene absorption across routes of exposure, especially pulmonary and gastrointestinal barriers. There exists substantial literature on pulmonary absorption in humans and a few laboratory animal species. Data on oral absorption in humans are lacking; hence extrapolation is based on gastrointestinal absorption studies in several experimental animal species. Currently, available physiologically based pharmacokinetic (PBPK) animal models are not useful for human risk extrapolation. A review of the relevant literature suggests absorption efficiencies of 50% and 100% for inhalation and oral routes of exposure, respectively. Application of these absorption factors to the current inhalation unit risk range of 2.2 × 10 – 7.8 × 10 per μg/m results in a proposed range for the oral unit risk of 4.4 × 10 to 1.6 × 10/μg/L.