Evaluating Lead Bioavailability Data by Means of a Physiologically Based Lead Kinetic Model

A method of bioavailability estimation is presented in whicha physiologically based kinetic model of lead kinetics is fitsimultaneously to blood and bone lead concentrations after aperiod of exposure to dietary lead. Optimization of the simultaneousfit, varying only fractional absorption, gives the best estimateof fractional bioavailability for each treatment group. Theanalysis was applied to data from three separate studies inwhich rats were fed for 30 consecutive days purified diets containinglead added as lead acetate, mine waste-contaminated test soils,or mine waste itself. Fractional absorption decreased as leadintake increased, regardless of the source of the lead; butthe magnitude of this dose dependence was lead source-dependent.There were no differences in lead absorption by male and femalerats when lead intake was expressed per unit body weight. Fractionalabsorption varied from 4 to 5%, at low exposure rates (1–2mg lead/kg/day) when lead acetate was added to the diet, to0.24% at a high exposure rate (24 mg/kg/day) when a mine waste-contaminatedtest soil was added to the diet. Comparison of the results ofthis analysis with the results of a more conventional analysis,in which the bone and blood lead concentrations were separatelycompared with bone and blood lead concentrations in rats givendaily injections of lead acetate intravenously for 29 consecutivedays, demonstrated that the standard analysis failed to revealthe dose dependence of fractional absorption.