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We conducted a study among residents of a small community contaminated with heavy metals from a defunct zinc smelter and residents from a comparison community to determine whether biologic measures of cadmium exposure were associated with biomarkers of early kidney damage. Creatinine-adjusted urinary cadmium levels did not differ between the smelter and comparison communities; thus we combined individuals from both communities (n = 361) for further analyses. The overall mean urinary cadmium level was low, 0.26 microg/g creatinine, similar to reference values observed in the U.S. general population. For children ages 6-17 years, urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and albumin were positively associated with urinary cadmium, but these associations did not remain statistically significant after adjusting for urinary creatinine and other potential confounders. For adults ages 18 or older, urinary concentration of NAG, AAP, and albumin were positively associated with urinary cadmium. The associations with NAG and AAP but not with albumin remained statistically significant after adjusting for creatinine and other potential confounders. We found a positive dose-effect relationship between levels of creatinine-adjusted urinary cadmium and NAG and AAP activity, and statistically significant differences in mean activity for these two enzymes between the highest (> or =1.0 microg cadmium/g creatinine) and the lowest (< or =0.25 microg cadmium/g creatinine) exposure groups. The findings of this study indicate that biologic measures of cadmium exposure at levels below 2.0 microg/g creatinine may produce measurable changes in kidney biomarkers.

To identify kidney injury and dysfunction among persons exposed to hazardous substances in the environment, a battery of biomarker tests has been identified for systematic public health use. The standardized use of tests for conducting field epidemiology studies was reviewed in a 1995 joint American-European workshop, and recommended tests were selected by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC). These tests would be useful in conducting public health activities but are not recommended in a manner that would suggest changes in routine clinical practice. The tests selected include serum creatinine, urine analysis, urinary albumin, retinol-binding protein, N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and osmolality. Urinary creatinine was also included to adjust for urine concentration. The tests were chosen for use not only in epidemiologic field studies but also clinically oriented population screening and case studies of persons exposed to hazardous substances at waste sites. Studies using the battery may address the relationship between kidney damage and dysfunction and exposures to hazardous substances, especially in susceptible populations including children. Also, longitudinal studies should be conducted to evaluate the long-term health implications of abnormal tests and to measure the tests' predictive value for renal injury. These studies could evaluate the continuum of renal dysfunction as expressed by persistent decrements in glomerular filtration to the development of end-stage renal disease.

To identify neurotoxic effects in children living near hazardous waste sites, the Agency for Toxic Substances and Disease Registry (ATSDR) has designed a basic Pediatric Environmental Neurobehavioral Test Battery (PENTB) for children 1 through 16 years of age. It emphasizes tests appropriate to the stages of a child's development. These stages were fundamental factors in selecting tests for the PENTB, which includes both informant- and performance-based assessment procedures. Assessment of children under 4 years of age is restricted to four informant-based instruments, to evaluate as many functions as possible while minimizing testing time and the professional expertise needed in the test setting. The assessment of children 4 through 16 years of age includes 10 performance-based tests to evaluate key functions within the cognitive, motor, and sensory domains analogous to functions affected by neurotoxic chemicals in adults. In all age groups, it is crucial to also assess family, cultural, economic, and other potentially confounding variables.

Information about human exposures to environmental agents is a crucial component of informed decisions about protection of public health. Results from an inventory of exposure-related databases are used to examine the value of exposure information for risk assessment, risk management, surveillance of status and trends, and epidemiologic studies. Findings indicate that current and future exposure-related databases should include (1) standardized procedures for the collection, storage, analysis, and reporting of data; (2) an enhanced ability to compare data over time, i.e., conduct comparison studies of "old" and "new" methods; (3) mechanisms for coordination and cooperation among public and private-sector organizations with respect to the design, maintenance, exchange, and review of information systems; (4) measurements of actual exposures and dose for relevant human populations; and (5) data collection, storage, and retrieval methods that permit easy manipulation of information for both model building and testing.

Exposure databases are useful for monitoring status and trends in environmental health. However, other supporting data are usually needed to infer human exposure or internal dose. Program planning and evaluation, environmental health surveillance, epidemiologic research, and contributions to international efforts are four major purposes for monitoring environmental exposure status and trends. Although databases play an important role in monitoring human exposure, certain methodological problems need to be overcome. The work group developed six criteria for meeting information needs for human exposure assessment. Areas that need attention are (1) specification of location, (2) specification of facility and chemical identifiers, (3) documentation of special populations at risk, (4) provision of early warning of new problems, (5) monitoring changes over time, and (6) enhancement of documentation. We tested these criteria by examining six available databases that might be used for monitoring exposure to contaminants in drinking water. Available data fell short of information needs. We drew four conclusions and offered several recommendations for each. First, available data systems lack adequate measures of human exposure. Second, data for monitoring exposures for many important population subgroups and environmental settings are inadequate. Third, an "early warning" system that monitors human exposures is needed. Fourth, designers of data-collection systems should consider the needs of users who monitor status and trends of human exposure.

Improper dumping and storage of hazardous substances and whether these practices produce significant human exposure and health effects are growing concerns. A sequential approach has been used by the Centers for Disease Control and the Agency for Toxic Substances and Disease Registry in investigating potential exposure to and health effects resulting from environmental contamination with materials such as heavy metals, volatile organic compounds, and pesticide residues at sites throughout the United States. The strategy consists of four phases: site evaluation, pilot studies of exposure or health effects, analytic epidemiology studies, and public health surveillance. This approach offers a logical, phased strategy to use limited personnel and financial resources of local, State, national, or global health agency jurisdictions optimally in evaluating populations potentially exposed to hazardous materials in waste sites. Primarily, this approach is most helpful in identifying sites for etiologic studies and providing investigative leads to direct and focus these studies. The results of such studies provide information needed for making risk-management decisions to mitigate or eliminate human exposures and for developing interventions to prevent or minimize health problems resulting from exposures that already have occurred.