Evaluation of urinary 1-nitropyrene metabolities as a biomarker for exposure to d

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Diesel exhaust (DE) represents a major source of ambient fine particulate matter air pollution (PM), and has been associated with both acute and chronic health effects. As recognition of the health hazards of diesel exhaust has increased, regulatory bodies have responded by proposing and enforcing ever-more stringent limits on permissible diesel emissions and levels of DE in workplaces and in the ambient environment. Advancements in engine technology mean that diesel engines are up to an order of magnitude less polluting than in the past. In spite of the large economic investment in reducing diesel emissions, it remains unclear whether these interventions have substantially reduced personal exposures to DE, or improved public health. Investigating the relationship between DE exposure and adverse health effects is hindered by inadequate methods of exposure assessment. These limitations include: lack of specificity for DE, poor correlation between personal and central monitor exposure metrics, inability to account for modifying effect of personal protective equipment or behavior on personal exposures, and failure to capture differences in personal exposure versus absorbed dose. The nitro-PAH, 1-nitropyrene (1-NP) has been proposed as a unique marker for DE, and can be used to quantify the contribution of DE to ambient PM. It is our hypothesis that measurements of 1-nitropyrene metabolites in human urine samples could be used as a biomarker of exposure to DE. Our primary hypothesis is that human exposure to diesel exhaust results in a dose-dependent increase in urinary excretion of 1-nitropyrene (1-NP) metabolites that would be a suitable basis for a biomarker of exposure. To evaluate this hypothesis we propose the following specific aims (1) Develop sensitive GC/NICI/MS methods for the determination of 1-nitropyrene metabolites in human urine. (2) Investigate the dose-response relationship for urinary 1-nitropyrene metabolite excretion in individuals with elevated occupational and environmental exposures to diesel exhaust. (3) We will investigate within and between subject variation in urinary excretion of 1-nitropyrene metabolites. These studies will provide proof-of-principle that 1-nitropyrene metabolite concentrations in human urine are useful biomarkers of exposure to DE. A biomarker of DE exposure will be important to accurately assess individual exposure to and dose from DE. The biomarker will be useful to assess the effectiveness of regulations and technical interventions designed to reduce DE exposures, and can be used in epidemiological investigations to determine whether reduction in DE emissions are associated with improvements in public health.