Modeling and Optimal Regulation of Erythropoiesis Subject to Benzene Intoxication

Abstract

Benzene (C(6)H(6)) is a highly flammable, colorless liquid. Ubiquitous exposures result from its presence in gasoline vapors, cigarette smoke, and industrial processes. Benzene increases the incidence of leukemia in humans when they are exposed to high doses for extended periods; however, leukemia risks in humans subjected to low exposures are uncertain. The exposure-dose- response relationship of benzene in humans is expected to be nonlinear because benzene undergoes a series of metabolic transformations, detoxifying and activating, resulting in various metabolites that exert toxic effects on the bone marrow. Since benzene is a known human leukemogen, the toxicity of benzene in the bone marrow is of most importance. And because blood cells are produced in the bone marrow, we investigated the effects of benzene on hematopoiesis (blood cell production and development). An age-structured model was used to examine the process of erythropoiesis, the development of red blood cells. This investigation proved the existence and uniqueness of the solution of the system of coupled partial and ordinary differential equations. In addition, we formulated an optimal control problem for the control of erythropoiesis and performed numerical simulations to compare the performance of the optimal feedback law and another feedback function based on the Hill function.