No abstract

Elevated levels of naturally occurring uranium in groundwater have been found in small geographic areas throughout the world. Relevant research was reviewed pertaining to natural and depleted uranium (DU) exposure and nephrotoxicity, including epidemiologic community-based and occupational studies, studies of Gulf War veterans exposed to DU, and experimental studies in animals. Occupational cohort studies do not provide evidence of an increased risk of kidney-related mortality among uranium-exposed workers. However, occupational and community-based studies of populations chronically exposed to elevated drinking-water concentrations of uranium provide some evidence of adverse renal effects, as assessed by biomarkers of proximal tubule damage such as urinary levels of glucose, calcium, and various low-molecular-weight proteins. Indications of proximal tubule effects, as evidenced by increased urinary β(2)-microglobulin and retinol binding protein levels, were also seen in the most recent follow-up surveillance study of Gulf War veterans exposed to DU. The reported β(2)-microglobulin levels in these studies were generally considered to be within normal limits, but the long-term implications of the observed variation in these levels are not established. The kidney was observed to be a target of uranium toxicity following oral and implantation exposure routes in several animal species. The interpretation and importance of the observed changes in biomarkers of proximal tubule function are important questions that indicate the need for additional clinical, epidemiological, and experimental research.

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The U.S. EPA's Integrated Risk Information System (IRIS) program has initiated a health assessment for polycyclic aromatic hydrocarbon (PAH) mixtures. The IRIS program develops EPA consensus scientific positions on potential human health effects from chronic exposure to chemicals. Currently, the IRIS database contains health assessments for the toxic effects of exposure to coke oven emissions, creosote, diesel emissions, and 15 individual PAH compounds. As a whole, these assessments do not consider issues related to the environmental occurrence of PAH compounds as complex mixtures. Risk assessment of PAH mixtures has been hindered by a lack of information on the composition and toxicity of specific mixtures, the components that contribute most to toxicity, and the interactions and differences in mode of action between components. The state-of-the-science has advanced