Health risk assessment epidemiological studies

On November 18-20, 1998, a workshop on Scientific Issues Relevant to the Assessment of Health Effects from Exposure to Methylmercury was conducted in Raleigh, North Carolina. The workshop was jointly sponsored by the U.S. Department of Health and Human Services (DHHS), the National Institute of Environmental Health Sciences (NIEHS), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the U.S. Environmental Protection Agency (EPA), the National Oceanic and Atmospheric Administration (NOAA), the Office of Science and Technology Policy (OSTP), the Office of Management and Budget (OMB), and ATSDR. The purpose of this workshop was to discuss and evaluate the major epidemiologic studies that associated methylmercury exposure and the results of an array of developmental measures in children. These studies monitored and evaluated exposed populations in Iraq, the Seychelles Islands, the Faroe Islands, and the Amazon River Basin. A number of animal studies were also considered in support of a human health risk assessment. 

To summarize the noncancer health risk-assessment process, chemicals of concern, pathways of exposure, and exposed populations are identified in the first step of the risk assessment, hazard identification. In the second step, analysis of exposure, the doses are estimated for each population, each exposure pathway, and each chemical of concern in the form of chronic daily intakes, or CDIs. In the third step of the risk assessment, analysis of effect, noncancer health effects are estimated by comparing CDIs to reference doses, or RfDs, derived from animal toxicity studies (with input from human epidemiological studies, when available). If the CDI is greater... 

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). 

Pharmacokinetics has played a crucial and somewhat unusual role in the assessment of health risks from methylmercury. Some of the epidemiology studies of this fish contaminant involved the measurement of mercury levels in the hair of pregnant women, and subsequent measurements of health outcomes in their offspring (Chapter 4). Various sets of pharmacokinetic data allowed estimation of the level of methylmercury intake through fish consumption (its only source) that gave rise to the measured levels in hair. In this way it was possible to identify the dose-response relationship in terms of intake, not hair level. Once the dose-response relationship was established in this way, the EPA was able to follow its usual procedure for establishing an RfD (which is 0.1 ag/(kg b.w. day)). 

Finding The ability to detect chemicals has outpaced the ability to interpret health risks. Epidemiologic, toxicologic, and exposure-assessment studies have not adequately incorporated biomonitoring data for interpretation of health risks at the individual, community, and population levels. 

The most important question for biomonitoring efforts to address is whether exposure to a chemical causes health effects. Few data are available on most of the chemicals measured in population studies, such as NHANES, to address that question (Metcalf and Orloff 2004). For example, the Government Accountability Office (GAO 2005) reports that EPA has limited data on the health and environmental risks posed by chemicals now used in commerce. A survey of risk-assessment practitioners on the extent to which biomarkers are used in risk assessment concluded that the absence of chemical-specific data (for example, toxicologic and epidemiologic data) was the primary limitation in using exposure biomarkers in risk assessment (Maier et al. 2004). 

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