NEW DIRECTIONS IN THE TOXICOKINETICS OF HUMAN LEAD-EXPOSURE

An important determinant of body lead (Pb) burden and Pb toxicity in e xposed humans is Pb metabolism, or more correctly, Pb toxicokinetics. It affects the former through the quantitative processes of uptake, di stribution and retention/excretion and the latter via delivery of toxi c doses to cellular/molecular sites of action. Pb toxicokinetics has u seful application in understanding Pb's behavior in populations. Sever al of these applications have been studied and results are presented f or the toxicokinetic basis of dose-neurotoxic effect relationships in selected longitudinal studies and the use of toxicokinetic modeling fo r estimation of body lead burden in early populations. Three well-know n, ongoing longitudinal studies of developmental neurotoxicity - in Bo ston, Cincinnati, and Port Pirie, Australia - involve cohorts who diff er markedly as to their pre- and postnatal lead exposure profiles. Tox icokinetic examination of these exposure differences helps to explain the temporal variability seen in blood Pb-toxic effect relationships a nd supports a causal role for lead Toxicokinetic models of Pb uptake a nd in-vivo behavior are increasingly being considered for estimating P b-B levels in lieu of direct measurement. A linear biokinetic model, u sing reliable input data for natural/prehistoric levels of Pb in sourc es, was applied to estimation of prehistoric/preindustrial children's blood lead. A range of 0.06 to 0. 12 mug/dl was estimated for two lead intakes. These estimates are still two orders of magnitude (85 to 165 -fold) lower than the newly issued CDC toxicity guideline for children of 10 mug/dl. Lastly, the toxicokinetics of lead in bone, particularl y its resorption with metabolic stimuli, is of concern, particularly f or ''baby boom'' women who are either of childbearing age or approachi ng menopause and who had greatly elevated environmental lead exposures in the 1940s to 1970s. (C) 1993 Intox Press, Inc.