Main Title |
Modeling Receptor-Mediated Processes with Dioxin: Implications for Pharmacokinetics and Risk Assessment. |
Author |
Andersen, M. E. ;
Mills, J. J. ;
Gargas, M. L. ;
Kedderis, L. ;
Birnbaum, L. S. ;
|
CORP Author |
Health Effects Research Lab., Research Triangle Park, NC. ;Chemical Industry Inst. of Toxicology, Research Triangle Park, NC. ;North Carolina Univ. at Chapel Hill. Center for Environmental Medicine and Lung Biology. ;Purdue Univ., Lafayette, IN. Dept. of Pharmacology and Toxicology. ;Freie Univ. Berlin (Germany, F.R.). Inst. fuer Toxikologie und Embryonalpharmakologie. |
Publisher |
c1993 |
Year Published |
1993 |
Report Number |
EPA/600/J-93/356; |
Stock Number |
PB93-228823 |
Additional Subjects |
Tetrachlorodibenzodioxin ;
Pharmacokinetics ;
Risk assessment ;
Carcinogens ;
Enzyme induction ;
Chemical models ;
Tissue distribution ;
Liver ;
Adipose tissue ;
Dose-response relationships ;
Carcinogenesis ;
Proteins ;
Binding sites ;
Reprints ;
Aryl hydrocarbon receptor
|
Holdings |
Library |
Call Number |
Additional Info |
Location |
Last Modified |
Checkout Status |
NTIS |
PB93-228823 |
Some EPA libraries have a fiche copy filed under the call number shown. |
|
07/26/2022 |
|
Collation |
14p |
Abstract |
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD), a widespread polychlorinated aromatic hydrocarbon, caused tumors in the liver and other sites when administered chronically to rats at doses as low as 0.0l microgram/kg/day. It functions in combination with a cellular protein, the Ah receptor, to alter gene regulation, and this resulting modulation of gene expression is believed to be obligatory for both dioxin toxicity and carcinogenicity. The paper describes a receptor-mediated physiologically based pharmacokinetic model for the tissue distribution and enzyme-inducing properties of dioxin and discusses the potential role of these models in a biologically motivated risk assessment. In the model, ternary interactions between the Ah receptor, dioxin, and specific DNA binding sites lead to enhanced production of specific hepatic proteins. The model was used to examine the tissue disposition of dioxin and the induction of both a dioxin-binding protein (presumably cytochrome P4501A2), and cytochrome P4501A1. |
Supplementary Notes |
Pub. in Risk Analysis, v13 n1 p25-36 Jan 93. Prepared in cooperation with Chemical Industry Inst. of Toxicology, Research Triangle Park, NC., North Carolina Univ. at Chapel Hill. Center for Environmental Medicine and Lung Biology, Purdue Univ., Lafayette, IN. Dept. of Pharmacology and Toxicology, and Freie Univ. Berlin (Germany, F.R.). Inst. fuer Toxikologie und Embryonalpharmakologie. |
NTIS Title Notes |
Journal article. |
Title Annotations |
Reprint: Modeling Receptor-Mediated Processes with Dioxin: Implications for Pharmacokinetics and Risk Assessment. |
Category Codes |
57Y; 57B |
NTIS Prices |
PC A03/MF A01 |
Primary Description |
600/10 |
Document Type |
NT |
Cataloging Source |
NTIS/MT |
Control Number |
329432323 |
Origin |
NTIS |
Type |
CAT |