||Physiologically Based Kinetic Model of Rat and Mouse Gestation: Disposition of a Weak Acid.
O'Flaherty, E. J. ;
Scott, W. ;
Schreiner, C. ;
Beliles, R. P. ;
||Environmental Protection Agency, Washington, DC. Office of Health and Environmental Assessment. ;Cincinnati Univ., OH. Coll. of Medicine. ;Children's Hospital Research Foundation, Cincinnati, OH.
||EPA/600/J-92/240 ;OHEA-C-021; EPA-R-815820-01;
Animal pregnancy ;
Biological models ;
Teratogenic compounds ;
Regional blood flow ;
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A physiologically based toxicokinetic model of gestation in the rat and mouse has been developed. The gestation model is based on published values of organ volumes and blood flows for the rat throughout pregnancy. It is scaled to the mouse using conventional scaling procedures. Its descriptive utility has been examined with the test chemical 5,5'-dimethyloxadolidine-2,4-dione (DMO), a weak acid that is not bound measurably in plasma or tissues and is eliminated by excretion in the urine. Concentrations of DMO were monitored in maternal rat and embryo plasma and in homogenates of maternal rat muscle and whole embryo after ip administration at 9:00 AM on Day 13 of gestation. On the basis that distribution of DMO is determined solely by its pK and the pH's of body fluids, pH and excretion rate values were estimated by visual optimization of model predictions to the concentration profile.