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Aging and Susceptibility to Environmental Stressors
Abstract:
In October 2002, the US EPA announced an Aging Initiative to develop a comprehensive and coordinated approach to addressing the environmental health concerns and risks that may confront the nation’s rapidly expanding population of older adults. This initiative was motivated by the realization that, with aging, our organ systems may become more vulnerable to environmental hazards (e.g., reduced reserve capacity) accompanied by a reduced capacity to detoxify and eliminate toxicants. Health effects resulting from a lifetime of toxicant exposures may also become manifest with age. EPA’s development of a research framework to address these issues has benefited from input derived from a December 2002 National Academy of Sciences (NAS) Workshop and six public meetings held throughout the United States in spring 2003. To address health issues, EPA has proposed to apply an environmental public health paradigm to better understand the relationships between external pollution sources, human exposures, internal dose, early biological effect, and adverse health effects for this sub-population. In addition to considering the health effects of exposures on healthy older adults, EPA will use information about aging-related changes in activity, exposure, pharmacokinetic, and pharmacodynamic factors to identify particularly susceptible or vulnerable sub-groups within this diverse population. Using a life-stage approach for human risk characterization based on differences in exposures and susceptibility, it will be important to identify the important sub-populations in the aging population with regard to environmental hazards. Data are needed regarding 1) behavior/activity patterns and physiology in the healthy older population and potentially susceptible subpopulations, 2) exposure to chemical and biological pollutants in populations of older adults; 3) prevalence and distribution of other stressors that may affect susceptibility to environmental exposures; 4) changes in absorption, distribution, metabolism, and excretion; and 5) alterations in reserve capacity that alter the body’s ability to compensate for the effects of environmental exposures. This task describes human activity and exposure research that is planned to address the first two areas as part of a collaborative ORD-wide research framework involving multiple labs and centers. Research on older adults’ exposures, activities, stressor, and their subsequent pharmcokinetic responses will reduce uncertainties in risk assessment through understanding and elucidating the fundamental determinants of exposure and dose. The information will be used by risk managers and risk assessors who need to incorporate the differential susceptibility of this heterogeneous group into decisions affecting risk and public health.
Objective:
The overall goal of this work is to develop information to assess potential environmental health risks and susceptibility in the aging population. Initial work will be directed toward developing information that can be used to identify and characterize what is known about activity, exposure, and dose for key life stages in the aging population and to identify key data gaps to be addressed through further research. Specific research objectives have been identified to address four discrete elements of the environmental paradigm for an aging population.
- Identify key chemical and biological stressors in the older adult population, compile extant information on exposures to these agents and the extent to which they may be different in aging and other populations, and identify key gaps in our knowledge of exposure to important stressors.
- Identify the key life stages in the older adult population with regard to exposures and susceptibilities to chemical and biological stressors. Compile activity pattern and physiological information for older Americans in key life stages, including information on physical activity, dietary intakes, pharmaceutical use, and other possible stressors that may impact exposures and/or susceptibility. Identify key gaps in our knowledge of activities in subpopulations of the aging by life stages.
- Incorporate changes in physiological parameters that result from aging in physiologically-based pharmacokinetic models. Assess the relative sensitivity of aging-related changes in parameters for generation of dose estimates. Determine which parameters may require additional knowledge to improve the models.
- Provide information developed for exposure, activity, and pharmacokinetics to extend existing exposure and PBPK models to aging populations and susceptible subpopulations at different life stages for use in risk assessment. Also, appropriate information will be provided for incorporation into an Older Adults Exposure Factors Handbook being prepared by NCEA.
Relevance/Significance/Impact:
Research on older adults’ exposures, activities, and their subsequent pharmcokinetic responses will reduce uncertainties in risk assessment through understanding and elucidating the fundamental determinants of exposure and dose. The information will be used by risk managers and risk assessors who need to incorporate the differential susceptibility of this heterogeneous group into decisions affecting risk and public health. This work will compile and consolidate existing data for use in exposure-to-dose and pharmacokinetic models applicable to aging populations, and will provide additional aging-specific information for the EPA’s Exposure Factors Handbook.
Principal Investigator: Kent W. Thomas