Abstract:
:A physiologically based pharmacokinetic (PBPK) model describing transfer of inhaled tetrachloroethylene (PCE) into breast milk with the consequent exposure of the nursing pups was developed and validated in lactating rats. The PBPK model was based on partition coefficients (PCs), which were determined by the equilibration of tissues with known concentrations of PCE vapor. The blood/air and milk/blood PCs for the dam were 33.5 and 12.0, the liver/blood and fat/blood PCs for the dam were 1.9 and 42.4, and the slowly perfused tissues/blood and rapidly perfused tissues/blood PCs for the dam were 0.9 and 1.7, respectively. The blood/air PC for the pup was 24.3, and the solid tissues/blood PC for the pup was 4.5. Metabolic constants were determined by a gas uptake method. The pseudo-maximal velocity of PCE metabolism in the dam was low, 0.03 mg/kg/hr, and the apparent Michaelis-Menten constant was 0.3 mg/liter. The lactating Sprague-Dawley females were exposed to PCE vapor for 2 hr with concentrations ranging from 20 to 1000 ppm PCE. The dams were returned to the pups after exposure and the pups received PCE via breast milk while they nursed. PCE concentrations in the air, blood, milk, and tissues were determined by gas chromatography and compared to PBPK model predictions. Nursing resulted in a peak pup blood PCE concentration of 0.9 mg/liter and a peak pup solid tissue PCE concentration of 8 mg/kg. The PBPK lactation model adequately described the distribution of inhaled PCE in maternal blood and milk, as well as in the nursed pup's gastrointestinal tract, blood, and solid tissues. It is concluded that the predictions based on PBPK modeling for disposition of PCE in lactating rats and their pups were in good agreement with the experimental data.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Byczkowski JZ,Kinkead ER,Leahy HF,Randall GM,Fisher JWdoi
10.1006/taap.1994.1068subject
Has Abstractpub_date
1994-04-01 00:00:00pages
228-36issue
2eissn
0041-008Xissn
1096-0333pii
S0041-008X(84)71068-4journal_volume
125pub_type
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