Epidemiological studies lead exposure measures

Two of the more interesting uses of pharmacokinetic data in risk assessment involve the neurotoxic agents lead and methylmercury (Chapter 4). In the case of lead, epidemiological studies have typically involved the development of quantitative relationships between levels of lead in the blood and adverse health effects. Other measures of lead in the body have also been used. Levels in blood are now very easy to measure, and they do carry the strong advantage that they integrate cumulative exposures from many possible sources (water, food, paint, soil, air, consumer products). Current public health targets for lead are expressed as blood concentrations, typically in pg/dL (Chapter 4). 

In the most straightforward risk-based approach, epidemiologic studies have developed exposure-response relationships based on biomarker measurements in hair, blood, urine, or other matrices (e.g., mercury, lead) (see Figure 5-2a). The relationships can be applied directly to new biomonitoring data to determine where on the exposure-response curve any person is. That may facilitate an understanding of risk, but it does not analyze sources of exposure, so other techniques (such as environmental sampling and behavioral surveys) may be needed to assess where the exposure came from. 

Since responses at the low dose levels of concern in routine exposures of the public cannot be measured directly in animal or human epidemiologic studies, a number of approaches have been developed to extrapolate from high to low doses. Different extrapolation approaches may fit the observed data reasonably well but lead to large differences in the projected responses at low doses (see Section 3.2.1.5.2). 

Exposure assessments may be conducted for one of four purposes hazard evaluation leading to appropriate control efforts, monitoring to ensure compliance with workplace standards, dose-response characterization within the context of epidemiological studies, and estimation of dose or uptake for risk assessments. Assessment strategies and measurement techniques will differ depending on the purpose at hand. 

A role for lead in hypertension gains further credence from epidemiologic studies of low-level lead exposure (i.e., exposure too low in intensity to produce the classic symptoms of acute lead poisoning). The Second National Health and Nutrition Examination Survey performed between 1976 and 1980 included blood lead and blood pressure measurements in almost... 

Tables 13.4 and 13.5 tabulate cross-sectional epidemiological data for nonoccupational populations sustaining cardiovascular effects from lead exposures using either PbB (Table 13.4) or bone Pb measurements (Table 13.5) as the exposure indicator and BP and/or hypertension as the toxic endpoints. The largest cohorts among these stodies used the exposure marker PbB the U.S. NHANES 11, NHANES 111, and more recent NHANES nationwide surveys (Den Hond et al., 2002 Muntner et al., 2005 Nash et al., 2003 Schwartz 1988 Scinicariello et al., 2010 Vupputuri et al., 2003) and the international surveys. Health Survey for England (HSE Bost et al., 1999), the British Regional Heart Study (BRHS Pocock et al., 1988), and the Belgian Cadmibel Study (BCS Staessen et al., 1993).

In summary, the PbB decay rates reported under experimental and epidemiological survey conditions indicate relatively short biological half-lives. The values of the half-lives vary with the type of study, e.g., length of survey and number of measurement points. For example, the lead-poisoned workers of Hryhorczuk et al (1985) showed a median PbB decay half-life of 619 days when followed for more than 5 years. The PbB curves for these subjects probably included more of the slow decay component than in any of the other reports. With an increase in lead exposure, adults appear to require ca. 60 days to return to exposure steady state, i.e., a rise in the PbB curve followed by a plateau. 

In the ten years since the results of the first epidemiological studies of the effects of low levels of lead were published, enormous progress has been made in almost all aspects of the research in study design, in the statistical techniques employed, in the outcome measures assessed, and in the measures of exposure. As a result of this we know a great deal more about the effects of low levels of environmental lead on developing children than we did a decade ago. The fact that there is still a lot that we do not know should not blind us to the achievements and progress that has been made. 

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