A mathematical model for dieldrin (HEOD) distributions in mammalian tissues is presented. The model is based upon lipid-phase transport of dieldrin, large tissue region compartments and destruction of dieldrin via enzymes in the liver. Several simple hypothetical cases involving a 300-gin mature male rat or a 68-kg mature male human are given. Realistic estimates of compartment masses, blood flow, and lipid content are provided, to illustrate the model's predictive potential. Discontinuous dieldrin administration is considered to illustrate procedural effects upon both blood and depot fat lipid-phase dieldrin concentrations.
A mathematical model simulating the blood transport and tissue residue distributions of the highly toxic and highly lipid soluble pesticide dieldrin in mammals is presented. This model is a significant improvement over our previously published preliminary model for dieldrin distribution in mammals. The assumptions and working hypotheses of the model are presented and used in generating a set of differential equations based upon mass balance principles. Two simulation cases are examined. The first simply demonstrates the gross features of: 1) Transport limiting conditions; 2) equal transport-equal membrane transfer conditions, and 3) membrane transfer limit conditions. The second studies a single tissue (the blood-brain barrier case) example of the above mentioned conditions. All simulations made were conducted for a hypothetical mature male rate of the average Wistar type eating food ad lib.
The preliminary model of the lipid-phase pharmacokinetics of dieldrin in mammals is applied to evaluation of the probable role of auto-induction, the effect(s) of growth, and the role of compartmentalization. Realistic simulations and comparison to actual data permit the conclusion to be drawn that induction of its own metabolism plays a relatively monor role in the distribution and level of dieldrin residues. Although some of the effects of growth are resonably well simulated, the model as constructed does not permit compartmentalization. It was concluded that the model should be revised to include aspects of the as-yet quantitatively unknown intracellular binding and membrane transport within the flow-limited model.
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