Lead exposure in early life: health consequences.
Until very recently it has been considered that of the many manifestations of lead toxicity, those involving the elaboration and function of hemoproteins occur at lower levels of lead exposure than any others. The critical target seems to be the enzyme heme synthetase, which is essential for the insertion of iron into the precursor, protoporphyrin IX. The major consequences of this effect, which have been evaluated in both adults and children, are reduction of circulating levels of hemoglobin and cytochrome P-450-dependent Phase I drug metabolism. Lead clearly inhibits normal hemoprotein function in both respects. The threshold level of lead exposure for these effects seems to be at a circulating lead concentration (PbB) of approximately 30 to 40 micrograms/dL. A growing body of evidence suggests, however, that the functional integrity of the central nervous system is compromised at substantially lower levels of lead exposure, particularly in the human fetus and young child. Early postnatal neurobehavioral development is compromised at maternal or cord PbB of somewhat less than approximately 10 micrograms/dL, a level of lead exposure not uncommon in the general population. Results of more recent cross-sectional and prospective studies indicate that postnatal lead exposure resulting in PbBs as low as 25 micrograms/dL, and probably lower, also are associated with deficits in intellectual attainment, achievement, and behavior. The long-term consequences of these effects remain to be fully evaluated. Little is known concerning basic mechanisms that are responsible for these effects. They may be manifestations of a more basic common effect of lead on cell proliferation and differentiation.
Hammond
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Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056.
Dietrich
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D000328:Adult; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D007223:Infant; D007854:Lead / Q000633:toxicity; D007855:Lead Poisoning / Q000175:diagnosis* / Q000209:etiology
D007854:Lead; D006418:Heme