Toward the twenty-first century: lessons from lead and lessons yet to learn.

A consideration of recent research on lead is instructive for developing research strategies in environmental toxicology. Lead research has demonstrated fruitful interactions between clinical and basic science. Thus, while epidemiological studies have suggested that central nervous system (CNS) effects in children are observed at the lowest increments of lead exposure, basic research has elucidated some of the molecular events that underly this lack of threshold at the neuronal level. Similarly, clinical studies indicate that early exposure to lead produces functionally irreversible damage to the CNS; experimental research demonstrates that this irreversibility may involve failure to remove lead from brain, permanent effects on synaptogenesis; and chelant-induced redistribution of lead from the periphery to the CNS. Lead toxicokinetics demand reevaluation. New data on release of bone stores of lead during physiological conditions of demineralization indicate that mobilization of bone lead adds to in utero exposure of the fetus. Furthermore, postmenopausal demineralization of bone can increase blood lead levels in women by 25%; this raises concern about the potential effects of lead in an aging population and the difficulties in comprehensive exposure assessment.