Lead concentration in whole blood (BPb) is the primary biomarker used to monitor exposure to this metallic element. The U.S. Centers for Disease Control and Prevention and the World Health Organization define a BPb of 10 μg/dL (0.48 μmol/L) as the threshold of concern in young children. However, recent studies have reported the possibility of adverse health effects, including intellectual impairment in young children, at BPb levels < 10 μg/dL, suggesting that there is no safe level of exposure. It appears impossible to differentiate between low-level chronic Pb exposure and a high-level short Pb exposure based on a single BPb measurement; therefore, serial BPb measurements offer a better estimation of possible health outcomes. The difficulty in assessing the exact nature of Pb exposure is dependent not so much on problems with current analytical methodologies, but rather on the complex toxicokinetics of Pb within various body compartments (i.e., cycling of Pb between bone, blood, and soft tissues). If we are to differentiate more effectively between Pb stored in the body for years and Pb from recent exposure, information on other biomarkers of exposure may be needed. None of the current biomarkers of internal Pb dose have yet been accepted by the scientific community as a reliable substitute for a BPb measurement. This review focuses on the limitations of biomarkers of Pb exposure and the need to improve the accuracy of their measurement. We present here only the traditional analytical protocols in current use, and we attempt to assess the influence of confounding variables on BPb levels. Finally, we discuss the interpretation of BPb data with respect to both external and endogenous Pb exposure, past or recent exposure, as well as the significance of Pb determinations in human specimens including hair, nails, saliva, bone, blood (plasma, whole blood), urine, feces, and exfoliated teeth.

BackgroundFew studies provide data directly relevant to the question of whether blood lead concentrations < 10 μg/dL adversely affect children’s cognitive function.ObjectiveWe examined the association between blood lead concentrations assessed throughout early childhood and children’s IQ at 6 years of age.MethodsChildren were followed from 6 months to 6 years of age, with determination of blood lead concentrations at 6, 12, 18, and 24 months, and 3, 4, 5, and 6 years of age. At 6 years of age, intelligence was assessed in 194 children using the Wechsler Preschool and Primary Scale of Intelligence–Revised. We used general linear and semiparametic models to estimate and test the association between blood lead concentration and IQ.ResultsAfter adjustment for maternal IQ, HOME scale scores, and other potential confounding factors, lifetime average blood lead concentration (mean = 7.2 μg/dL; median = 6.2 μg/dL) was inversely associated with Full-Scale IQ (p = 0.006) and Performance IQ scores (p = 0.002). Compared with children who had lifetime average blood lead concentrations < 5 μg/dL, children with lifetime average concentrations between 5 and 9.9 μg/dL scored 4.9 points lower on Full-Scale IQ (91.3 vs. 86.4, p = 0.03). Nonlinear modeling of the peak blood lead concentration revealed an inverse association (p = 0.003) between peak blood lead levels and Full-Scale IQ down to 2.1 μg/dL, the lowest observed peak blood lead concentration in our study.ConclusionsEvidence from this cohort indicates that children’s intellectual functioning at 6 years of age is impaired by blood lead concentrations well below 10 μg/dL, the Centers for Disease Control and Prevention definition of an elevated blood lead level.