A pilot study of oral bioavailability of dioxins and furans from contaminated soils: Impact of differential hepatic enzyme activity and species differences R.A. Budinsky a, * , J.C. Rowlands a , S. Casteel b , G. Fent b , C.A. Cushing c , J. Newsted d , J.P. Giesy e , M.V. Ruby f , L.L. Aylward g a The Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland, MI, USA b The University of Missouri, Columbia, MO, USA c Exponent Inc., Chicago, IL, USA d Entrix Inc., East Lansing, MI, USA e The University of Saskatchewan Saskatoon, SK S7N 5B3, Canada f Boulder, Colorado, USA g Summit Toxicology, LLP, Falls Church, VA, USA Received 16 April 2007; received in revised form 27 July 2007; accepted 19 August 2007 Available online 22 October 2007 Abstract An in vivo pilot study of the oral bioavailability of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in two soils with distinct congener profiles (one dominated by PCDDs, the other by PCDFs) was conducted in rats and juvenile swine. The pilot study revealed potential confounding of relative bioavailability estimates compared to bioavailability in spiked corn oil gavage for tetrachlorodibenzofuran (TCDF) in the rat study due to differential EROD induction between groups receiving soil and those receiving spiked control PCDDs/PCDFs. A follow-up study in rats with the furan-contaminated soil was then conducted with reductions in the spiked control doses to 20%, 50% and 80% of the soil-feed dose in order to bracket hepatic enzyme induction levels in the soil group. When hepatic enzyme induction was matched between the soil and spiked control groups, the apparent relative bioavailability for TCDF was reduced significantly. Overall, after controlling for hepatic enzyme induction, estimates of relative bioavailability in rats and swine differed for the two soils. In the rat study, the relative bioavailability of the two soils were approximately 37% and 60% com- pared to corn oil administration for the PCDD- and PCDF- dominated soils, respectively, on a TEQ basis. In swine, both soils demon- strated relative bioavailability between 20% and 25% compared to administration in corn oil. These species differences and experimental design issues, such as controlling for differential enzyme induction between corn oil and soil-feed animals in a bioavailability study, are relevant to risk assessment efforts where relative bioavailability inputs are important for theoretical exposure and risk characterization. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Dioxin; Furans; Bioavailability; Soils; Swine; Rats 1. Introduction Bioavailability directly impacts exposure potential to chlorinated dibenzo-p-dioxins and furans (PCDD/Fs) pres- ent in soil and sediment. Soil aging and the presence of organic carbon, such as black carbon, are believed to reduce oral bioavailability for hydrophobic compounds such as PCDD/Fs (Poiger and Schlatter, 1986; Alexander, 2000; Koelmans et al., 2006). Oral bioavailability studies of soils containing 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit a range of relative (RBA) and absolute bioavailability of approximately 10% to 40% and 10% to 30%, respectively (Bonaccorsi et al., 1984; McConnell 0045-6535/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.chemosphere.2007.08.035 * Corresponding author. Tel.: +1 989 638 7644. E-mail address: rabudinsky@dow.com (R.A. Budinsky). www.elsevier.com/locate/chemosphere Available online at www.sciencedirect.com Chemosphere 70 (2008) 1774–1786