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ToxSci Advance Access published online on December 2, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfh033
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received June 4, 2003; accepted October 23, 2003
© 2003 Society of Toxicology

Biotransformation and Toxicokinetics

A Physiologically Based Toxicokinetic Model for Dietary Uptake of Hydrophobic Organic Compounds by Fish I. Feeding Studies with 2,2',5,5'-Tetrachlorobiphenyl

John W. Nichols 1*, Patrick N. Fitzsimmons 1, Frank W. Whiteman 1, Timothy D. Dawson 2, Leo Babeu 2, and Jamie Juenemann 2

1 U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, Minnesota, 55804
2 AScI Corporation, 4444 Airpark Boulevard, Duluth, Minnesota 55811

* To whom correspondence should be addressed. E-mail: nichols.john{at}epa.gov.


  Abstract

A physiologically based toxicokinetic (PBTK) model was developed to describe dietary uptake of hydrophobic organic compounds by fish. The gastrointestinal (GI) tract was modeled using four compartments corresponding to the stomach, pyloric ceca, upper intestine, and lower intestine, and the lumenal volume of each compartment was allowed to change in time as a function of bulk flow down the GI tract and (for the pyloric ceca and upper intestine) nutrient uptake. The model was developed using data from rainbow trout that were fed a single meal of 60 d-old fathead minnows contaminated with [UL-14C] 2,2',5,5'-tetrachlorobiphenyl ([14C] PCB 52). Chemical partitioning coefficients for the gut contents and tissues were adjusted to account for changes in chemical affinity associated with uptake of dietary lipid. Permeability constants for the absorbing gut segments were then fitted by modeling to measured [14C] PCB 52 concentrations in gut contents and tissues. The model accurately describes observed patterns of gastric evacuation and bulk flow of digesta, the concentration time-course for [14C] PCB 52 in contents and tissues of the GI tract, and [14C] PCB 52 distribution to other major tissues. Most of the [14C] PCB 52 was taken up in the pyloric ceca and upper intestine during the period of peak lipid absorption. It is concluded, however, that a kinetic limitation acting along the entire length of the GI tract resulted in a chemical disequilibrium between feces and tissues of the lower intestine.


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J. W. Nichols, P. N. Fitzsimmons, and F. W. Whiteman
A Physiologically Based Toxicokinetic Model for Dietary Uptake of Hydrophobic Organic Compounds by Fish: II. Simulation of Chronic Exposure Scenarios
Toxicol. Sci., February 1, 2004; 77(2): 219 - 229.
[Abstract] [Full Text] [PDF]


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