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DISPOSITION AND EXCRETION OF INTRAVENOUS 2,3,7,8-TETRABROMODIBENZO-P-DIOXIN (TBDD) IN RATS
Citation:
Kedderis, L. AND e. al. DISPOSITION AND EXCRETION OF INTRAVENOUS 2,3,7,8-TETRABROMODIBENZO-P-DIOXIN (TBDD) IN RATS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/123 (NTIS PB91211466).
Description:
Polybrominated dibenzodioxins and dibenzofurans are of toxicologic interest due to potential occupational and environmental exposure and because of their structural similarity to the highly toxic chlorinated analogues. he excretion and terminal tissue distribution of 3H-TBDD was studied in male F344 rats for 56 days following single doses of 0, 0.001 or 0.1 umol/kg. he major tissue depots of radioactivity in liver, adipose, and skin, and tissue distribution was dose-dependent. t 56 days, liver concentrations in the high dose group were disproportionately increased compared to the low dose group. iver:adipose concentration ratios were 0.2 and 2.6 at the low and high doses, respectively. limination of radioactivity in the feces, the major route of excretion, and urine was also nonlinear with respect to dose. y day 56, feces accounted for approximately 50% of the administered dose at the low dose versus 70% at the high dose. ased on fecal excretion, the apparent terminal whole body half-life was estimated to be 18 days for both dose groups. he time-dependent pattern of tissue disposition was characterized at the low dose over 56-day period. lood levels of radioactivity declined rapidly with -2% remaining in the blood by 24 hours. adioactivity levels in the liver peaked by 7 hrs and then gradually declined concomitant with a slow accumulation in adipose tissue. he terminal excretion half-life of radioactivity In adipose was estimated to be -6O days. iver:adipose concentration ratios declined with time. hus, the overall disposition of TBDD appears similar to that observed for the chlorinated analogue, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). he dose-dependent tissue disposition and excretion kinetics of these compounds suggest important considerations for extrapolations from high to low doses.
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DISPOSITION AND EXCRETION OF INTRAVENOUS 2,3,7,8-TETRABROMODIBENZO-P-DIOXIN (TBDD) IN RATS