The effect of dose on the disposition of lead in rats after intravenous and oral administration

Single doses of lead acetate were administered to 250- to 350-g rats by both iv (0.5-15 mg Pb/kg) and po (1-100 mg Pb/kg) routes, and blood lead concentrations were measured up to 25 days following dosing. The area under the blood lead concentration vs time curve (AUC) after iv dosing increased in proportion to increases in the dose. Total blood lead clearance and renal lead clearance were not related to the magnitude of the injected dose. After oral dosing, blood lead concentrations (and AUC) did not increase proportionately with dose. After a 1 mg/kg po lead dose, the extent of absorption was estimated at 42%; this decreased to 2% when the dose was increased to 100 mg/kg. Lead concentrations in the blood, kidneys, liver, and brain of both adult and suckling rats recovered 24 hr after various single po doses also indicated that the extent of lead absorption decreased substantially with increasing dose. Blood and kidney lead concentrations in adult rats exposed for 14 days to lead via drinking water also were not proportional to the apparent amount of lead ingested. The results are consistent with published in vitro data which suggested that the mechanism for gastrointestinal absorption of lead is largely capacity-limited in adolescent and adult rats. Because blood lead concentrations were not a linear function of the oral dose in the rat, the relationship between oral dose and toxic effects of lead may not be a simple one. This factor should be considered when safe lead exposure levels in man are to be established via extrapolation of data from high levels of exposure.