State of the art of cognitive and other CNS effects of lead exposure in children

Many times in the history of lead toxicology the view has prevailed that “the problem” has been solved, and that exposure to lead is no longer a major public health concern. Each time, additional research has demonstrated the prematurity of this judgment.  In the last decade, an extraordinary number of new studies have illustrated that “the problem” remains, and that it has dimensions never before considered.   Children’s intelligence has traditionally been considered to be the most sensitive endpoint and used as the basis for risk assessment and standard setting.  For IQ, the dose-effect relationship appears to be supra-linear, with greater deficits per microg/L increment below than above 100 microg/L.  Recent studies have found that greater lead exposure in early childhood is also associated with a wide variety of other outcomes, with some associations evident at biomarker levels comparable to those at which IQ deficits are observed.  Among these endpoints are behavioral disorders such as ADHD, antisocial behavior, delayed sexual maturation, and impaired dental health. Another recent finding is that blood lead levels measured in childhood are stronger predictors of adverse outcomes than are levels measured earlier, including prenatally.   In animals, early life lead exposure has been implicated in neurodegenerative disorders later in life, perhaps via epigenetic mechanisms.  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. Several recent risk assessments (e.g., EFSA, JECFA) have concluded that research has yet to identify a threshold level below which lead can be considered “safe.”