The protean toxicities of lead: new chapters in a familiar story.

Many times in the history of lead toxicology the view that "the problem" has been solved and is no longer a major health concern has prevailed, only to have further research demonstrate the prematurity of this judgment. In the last decade, an extraordinary amount of new research on lead has illustrated, all too clearly, that "the problem" has not disappeared, and that, in fact, it has dimensions never before considered. Recent risk assessments have concluded that research has yet to identify a threshold level below which lead can be considered "safe." Although children's intelligence has traditionally been considered to be the most sensitive endpoint, and used as the basis for risk assessment and standard setting, increased lead exposure has been associated with a wide variety of other morbidities both in children and adults, in some cases at biomarker levels comparable to those associated with IQ deficits in children. In adults, these endpoints include all-cause mortality and dysfunctions in the renal, cardiovascular, reproductive, central nervous systems. In children, IQ deficits are observed at blood lead levels well below 10 μg/dL, and the dose-effect relationship appears to be supra-linear. Other health endpoints associated with greater early-life lead exposure in children include ADHD, conduct disorder, aggression and delinquency, impaired dental health, and delayed sexual maturation. Studies employing neuroimaging modalities such as volumetric, diffusion tensor, and functional MRI are providing insights into the neural bases of the cognitive impairments associated with greater lead exposure.