cognitive damage to children since the pioneering work of Byers and Lord (1943). Historically, assessment of the neuropsychologic effects of lead has been hampered by inadequate markers of exposure; i.e., blood lead is a short-term marker, and levels may return to normal after exposure has ended (Needleman, 1986), even though subjects' past exposures have caused persistent physiologic effects. One approach to the exposure-assessment issue is use of lead in shed deciduous teeth as a marker of past exposures. In a cohort study, first- and second-grade students who were considered asymptomatic for lead were classified by dentin lead levels and then evaluated with a battery of neuropsychologic tests (Needleman et al., 1979). Children with high dentin lead scored significantly less well on the Wechsler Intelligence Scale for Children (revised), on 3 measures of auditory speech processing, and on a measure of attention (Needleman et al., 1982). The authors concluded that lead, at doses below those that produce clinical symptoms, is associated with impaired neurobehavioral functioning (Needleman, 1986).
Although recent studies have found negative associations between blood lead concentrations and the full-scale intelligence quotient (IQ), not all have been statistically significant after control for some potential confounders (Needleman et al., 1979; Fulton et al., 1987; Hatzakis et al., 1987; Fergusson et al., 1988; Yule et al., 1981; Lansdown et al., 1986; Schroeder et al., 1985; Hawk et al., 1986; Bellinger et al., 1987). These studies are supported by studies in animals. In primates, Rice and Wiles (1979) found learning and attention-deficit disorders. Studies in rodents have shown cognitive disorders and interference with the dopaminergic system in the brain (Cory-Schlecta et al., 1981). Inhibition of long-term potentiation in the hippocampal region by lead (Munoz et al., 1988) has also been demonstrated in rats at moderate blood lead levels, which is again consistent with learning disorders. Meta-analyses of the human data have reported evidence for the association (Needleman and Gatsonis, 1990; Schwartz et al., 1985). These associations may or may not indicate a cause-effect relation (see discussion in NRC, 1993).
Several lessons may be drawn from these studies. First, a toxicant may have numerous neurologic effects, though it may be difficult to measure real but subtle behavioral changes. Second, markers of neurotoxic effect are often obtained simultaneously with markers of dose, making it difficult to discern the temporal or pathologic sequence of exposure, dose, and response. Third, neurotoxicant-induced alterations of neurobehavioral, neurophysiologic, and neurochemical function are believed to precede morphologic evidence of toxicity and to be more sensitive. However, functional indicators can be compromised by the adaptive capacity of the individual, especially with moderate to low levels of exposure. If the function of the nervous system is viewed as an adaptive process, it is