Toxicological considerations in the assessment of lead exposure

Many uncertainties remain today concerning effects of lead on the nervous system, particularly in regard to levels of lead exposure causing minimal brain dysfunction in children. Past studies in children have failed to define adequately the nature of the effect, the critical period and duration of exposure and the role of other factors in rendering the developing organism susceptible to lead. Prospective studies now underway should contribute greatly to the resolution of these issues. The studies propose to monitor both lead exposure and behavior at fixed intervals from birth for up to five years. The index of exposure in all studies is blood lead concentration. Test batteries vary considerably among studies, but most propose to include the Bayley Scales and the McCarthy Scales. These design features should greatly facilitate comparison of results across the studies. In the design of animal studies certain standardized features across studies also seem desirable, particularly concerning the characterization of lead exposure. Repeat measures of blood lead concentration in rats receiving lead via dams' milk and via water after weaning indicate that the response of individual animals is extremely variable, both as to the pattern of lead build-up and as to the degree of exposure. It is to be expected that biological responses would vary accordingly. It also follows that dose-response and dose-effect relationships in animal studies should be analyzed taking into account this problem. Data analysis should consider the dose and response of each animal individually. In the design of dosage regimens the profile of blood lead levels in adults and young children reported in the literature are useful guidelines in the design of exposure regimens. Many studies are concerned with non-behavioral aspects of lead toxicity e.g. disposition of neurotransmitters, morphological features of brain maturation and alterations in blood-brain barrier function. It would be extremely useful to relate the findings to some fairly standardized behavioral endpoint as well as to well-defined blood lead profiles.