The conceptual structure of the integrated exposure uptake biokinetic model for lead in children.

The integrated exposure uptake biokinetic model for lead in children was developed to provide plausible blood lead distributions corresponding to particular combinations of multimedia lead exposure. The model is based on a set of equations that convert lead exposure (expressed as micrograms per day) to blood lead concentration (expressed as micrograms per deciliter) by quantitatively mimicking the physiologic processes that determine blood lead concentration. The exposures from air, food, water, soil, and dust are modeled independently by several routes. Amounts of lead absorbed are modeled independently for air, food, water, and soil/dust, then combined as a single input to the blood plasma reservoir of the body. Lead in the blood plasma reservoir, which includes extracellular fluids, is mathematically allocated to all tissues of the body using age-specific biokinetic parameters. The model calculation provides the estimate for blood lead concentration for that age. This value is treated as the geometric mean of possible values for a single child, or the geometric mean of expected values for a population of children exposed to the same lead concentrations. The distribution of blood lead concentrations about this geometric mean is estimated using a geometric standard deviation, typically 1.6, derived from the analysis of well-conducted community blood studies.

Some useful statistical methods for model validation.

Although formal hypothesis tests provide a convenient framework for displaying the statistical results of empirical comparisons, standard tests should not be used without consideration of underlying measurement error structure. As part of the validation process, predictions of individual blood lead concentrations from models with site-specific input parameters are often compared with blood lead concentrations measured in field studies that also report lead concentrations in environmental media (soil, dust, water, paint) as surrogates for exposure. Measurements of these environmental media are subject to several sources of variability, including temporal and spatial sampling, sample preparation and chemical analysis, and data entry or recording. Adjustments for measurement error must be made before statistical tests can be used to empirically compare environmental data with model predictions. This report illustrates the effect of measurement error correction using a real dataset of child blood lead concentrations for an undisclosed midwestern community. We illustrate both the apparent failure of some standard regression tests and the success of adjustment of such tests for measurement error using the SIMEX (simulation-extrapolation) procedure. This procedure adds simulated measurement error to model predictions and then subtracts the total measurement error, analogous to the method of standard additions used by analytical chemists.

Current issues in human lead exposure and regulation of lead.

Concern about lead as a significant public health problem has increased as epidemiological and experimental evidence has mounted regarding adverse health effects at successively lower levels of lead exposure. This concern has led to downward revision of criteria for acceptable blood lead concentrations to the 10 micrograms/dL mark now designated by EPA as a target level for regulatory development and enforcement/clean-up purposes. Much progress has been made in reducing lead exposures during the past 10-15 years, with marked declines evident both in air lead and blood lead concentrations in parallel to the phase-down of lead in gasoline and notable decreases in food lead exposure due to elimination of lead soldered cans by U.S. food processors. With the lessening of exposure from these sources, the importance of other components of multimedia exposure pathways has grown and stimulated increasing regulatory attention and abatement efforts to reduce health risks associated with lead exposure from drinking water, from lead-based paint, and from household dust and soil contaminated by deteriorating paint, smelter emissions, or various other sources. Increasing attention is also being accorded to reduction of occupational lead exposures (including those related to lead abatement activities), with particular concern for protection of men and women during their reproductive years.