Contemporary Approaches to Assessing the Gastrointestinal Bioavailability of Organic Compounds within Complex Mixtures: Potential Application in Risk-Assessment. E. H. Weyand, B-L. Ma, and A. Yarborough, Department of Pharmaceutical Chemistry, Rutgers-The State University of New Jersey, College of Pharmacy, PO Box 789, Piscataway, NJ 08855-0789
The biological effects of organic compounds can be significantly modulated by sorption to soil. Numerous studies using whole animal systems have demonstrated that the in vivo bioavailability of organic compounds in soil is generally reduced when compared to pure compounds. Factors such as soil characteristics, compound molecular weight, age of contamination, level of contamination as well as a number of other factors have been shown to play a role in influencing the gastrointestinal bioavailability of organic compounds from soil. However, the emphasis of many of these studies was to identify the potential modulating effects of soil and not to address the issue of bioavailability within risk-based management. In addition, limited studies have attempted to characterize the relationship between bioavailability and a biological endpoint such as tumor induction. In order to fully utilize the concept of bioavailability in risk-assessment, it is essential to develop and use appropriate experimental approaches that can adequately define the properties and/or mechanism(s) responsible for reducing the gastrointestinal bioavailability of organic compounds sorbed to soil. In addition, the relationship between bioavailability and a defined biological endpoint pertinent to human risk is particularly important in validating the significance of reduced bioavailability. This presentation will discuss recent approaches in the assessment of the bioavailability of organic compounds from environmental complex mixtures. In particular, the effect of soil on the bioavailability of polycyclic aromatic hydrocarbons (PAH) present in manufactured gas plant residue will be presented. The use of monitoring urine PAH metabolite excretion, PAH:DNA adduct formation, and enzyme induction for characterizing bioavailability will be reviewed. Studies that investigated the relationship between bioavailability and parameters such as PAH dose and soil characteristics using contaminated soil from manufactured gas plant sites will be presented.
Supported by EPRI Contract RP 2963-01 and WO 9039-06.