TY - JOUR
T1 - A physiologically based toxicokinetic model for the uptake and disposition of waterborne organic chemicals in fish
AU - Nichols, John W.
AU - McKim, James M.
AU - Andersen, Melvin E.
AU - Gargas, Michael L.
AU - Clewell, Harvey J.
AU - Erickson, Russell J.
N1 - Funding Information:
This work was sponsored by the Air Force Office of Scientific Research, Air Force Systems Command, U.S. Air Force, under Grant AFOSR-ISSA-89-0060. The authors thank Gregory Lien, Alex Hoffman, Patrick
PY - 1990/12
Y1 - 1990/12
N2 - A physiologically based toxicokinetic model was developed to predict the uptake and disposition of waterborne organic chemicals in fish. The model consists of a set of mass-balance differential equations which describe the time course of chemical concentration within each of five tissue compartments: liver, kidney, fat, and richly perfused and poorly perfused tissue. Model compartmentalization and blood perfusion relationships were designed to reflect the physiology of fishes. Chemical uptake and elimination at the gills were modeled as countercurrent exchange processes, limited by the chemical capacity of blood and water flows. The model was evaluated by exposing rainbow trout (Oncorhynchus mykiss) to pentachloroethane (PCE) in water in fish respirometer-metabolism chambers. Exposure to 1500, 150, or 15 μg PCE/liter for 48 hr resulted in corresponding changes in the magnitude of blood concentrations without any change in uptake kinetics. The extraction efficiency for the chemical from water decreased throughout each exposure, declining from 65 to 20% in 48 hr. Extraction efficiency was close to 0% in fish exposed to PCE to near steady state (264 hr), suggesting that very little PCE was eliminated by metabolism or other extrabranchial routes. Parameterized for trout with physiological information from the literature and chemical partitioning estimates obtained in vitro, the model accurately predicted the accumulation of PCE in blood and tissues, and its extraction from inspired water. These results demonstrate the potential utility of this model for use in aquatic toxicology and environmental risk assessment.
AB - A physiologically based toxicokinetic model was developed to predict the uptake and disposition of waterborne organic chemicals in fish. The model consists of a set of mass-balance differential equations which describe the time course of chemical concentration within each of five tissue compartments: liver, kidney, fat, and richly perfused and poorly perfused tissue. Model compartmentalization and blood perfusion relationships were designed to reflect the physiology of fishes. Chemical uptake and elimination at the gills were modeled as countercurrent exchange processes, limited by the chemical capacity of blood and water flows. The model was evaluated by exposing rainbow trout (Oncorhynchus mykiss) to pentachloroethane (PCE) in water in fish respirometer-metabolism chambers. Exposure to 1500, 150, or 15 μg PCE/liter for 48 hr resulted in corresponding changes in the magnitude of blood concentrations without any change in uptake kinetics. The extraction efficiency for the chemical from water decreased throughout each exposure, declining from 65 to 20% in 48 hr. Extraction efficiency was close to 0% in fish exposed to PCE to near steady state (264 hr), suggesting that very little PCE was eliminated by metabolism or other extrabranchial routes. Parameterized for trout with physiological information from the literature and chemical partitioning estimates obtained in vitro, the model accurately predicted the accumulation of PCE in blood and tissues, and its extraction from inspired water. These results demonstrate the potential utility of this model for use in aquatic toxicology and environmental risk assessment.
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U2 - 10.1016/0041-008X(90)90338-U
DO - 10.1016/0041-008X(90)90338-U
M3 - Article
C2 - 2260091
AN - SCOPUS:0025632946
SN - 0041-008X
VL - 106
SP - 433
EP - 447
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -