EVALUATING LEAD BIOAVAILABILITY DATA BY MEANS OF A PHYSIOLOGICALLY-BASED LEAD KINETIC-MODEL

A method of bioavailability estimation is presented in which a physiol ogically based kinetic model of lead kinetics is fit simultaneously to blood and bone lead concentrations after a period of exposure to diet ary lead. Optimization of the simultaneous fit, varying only fractiona l absorption, gives the best estimate of fractional bioavailability fo r each treatment group. The analysis was applied to data from three se parate studies in which rats were fed for 30 consecutive days purified diets containing lead added as lead acetate, mine waste-contaminated test soils, or mine waste itself. Fractional absorption decreased as l ead intake increased, regardless of the source of the lead; but the ma gnitude of this dose dependence was lead source-dependent. There were no differences in lead absorption by male and female rats when lead in take was expressed per unit body weight, Fractional absorption varied from 4 to 5%, at low exposure rates (1-2 mg lead/kg/day) when lead ace tate was added to the diet, to 0.24% at a high exposure rate (24 mg/kg /day) when a mine waste-contaminated test soil was added to the diet. Comparison of the results of this analysis with the results of a more conventional analysis, in which the bone and blood lead concentrations were separately compared with bone and blood lead concentrations in r ats given daily injections of lead acetate intravenously for 29 consec utive days, demonstrated that the standard analysis failed to reveal t he dose dependence of fractional absorption. (C) 1996 Society of Toxic ology