A pilot study of oral bioavailability of dioxins and furans from contaminated soils: Impact of differential hepatic enzyme activity and species differences.
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% compared to corn oil administration for the PCDD- and PCDF- dominated soils, respectively, on a TEQ basis. In swine, both soils demonstrated 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.
Budinsky
R A
RA
The Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland, MI, USA. rabudinsky@dow.com
Rowlands
J C
JC
Casteel
S
S
Fent
G
G
Cushing
C A
CA
Newsted
J
J
Giesy
J P
JP
Ruby
M V
MV
Aylward
L L
LL
D000818:Animals; D001572:Benzofurans / Q000032:analysis / Q000493:pharmacokinetics*; D001682:Biological Availability; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000072338:Dibenzofurans, Polychlorinated; D005260:Female; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism; D010316:Particle Size; D010865:Pilot Projects; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012989:Soil Pollutants / Q000032:analysis / Q000493:pharmacokinetics*; D013045:Species Specificity; D013552:Swine
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D000072317:Polychlorinated Dibenzodioxins; D012989:Soil Pollutants; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1