Disposition of 2,3,7,8-tetrabromodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat: biliary excretion and induction of cytochromes CLP1A1 and CYP1A2

Technical Report · Wed Jan 01 04:00:00 EST 1992

OSTI ID:5441133

Kedderis, L B; Diliberto, J J; Linko, P; Goldstein, J A; Birnbaum, L S

The biologic activity and pharmacokinetic properties of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) are similar to those of the chlorinated congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Metabolism of both compounds appears to be rate-limiting for excretion, which is primarily via the feces. Therefore, the biliary elimination of TBDD and TCDD was examined as an indirect assessment of metabolism. Male F344 rats were anesthetized with pentobarbital, and 1 nmol/kg (3H)TBDD or (3H)TCDD was administered iv. Bile was collected for up to 8 hr while rats were maintained under anesthesia. In a second set of studies, the dose-response profiles for induction of cytochromes CYP1A1 and CYP1A2 by TBDD were characterized. The ED50 value for CYP1A1 induction (measured by ethoxyresorufin O-deethylase activity and radioimmunoassay (RIA)) was estimated to be 0.8-1.0 nmol/kg, similar to what has been reported for TCDD. Induction of CYP1A2 (RIA) by TBDD appeared to be a more sensitive response over the dose range studied. Finally, comparison of hepatic CYP1A2 induction vs hepatic concentrations of TBDD 3 days following treatment with 10 vs 1 nmol/kg TBDD suggested that induction of CYP1A2 alone may not account for nonlinearities in dioxin disposition exemplified by dose-related increases in the ratio of dioxin concentrations in liver and adipose tissue.

• Research Organization: Health Effects Research Lab., Research Triangle Park, NC (United States). Environmental Toxicology Div.
• OSTI ID: 5441133
• Report Number(s): PB-92-150747/XAB; EPA--600/J-92/060
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADIPOSE TISSUE
ANIMAL TISSUES
ANIMALS
BILE
BIOASSAY
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CONNECTIVE TISSUE
CYTOCHROMES
DIAGNOSTIC TECHNIQUES
DIGESTIVE SYSTEM
DIOXIN
DOSE-RESPONSE RELATIONSHIPS
ENZYME INDUCTION
FECES
GENE REGULATION
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
LIVER
MAMMALS
MATERIALS
METABOLISM
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PIGMENTS
PROTEINS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
RATS
RODENTS
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
WASTES