NORA Manufacturing Sector Strategic Goals
9278011 - Risk Assessment Methods for Particles and FibersStart Date: 10/1/1999
End Date: 9/30/2011
Principal Investigator (PI)Name: Eileen Kuempel
Funded By: NIOSH
Primary Goal Addressed5.0
Secondary Goal Addressed
Attributed to Manufacturing
The purpose of this research is to develop a mechanistic and scientific basis for quantitative risk assessment of occupational exposure to respirable particulates and fibers. This is being performed through the use of both traditional risk assessment methods and the development of biologically-based modeling using existing data in humans and animals. The concordance between the animal- and human-based risk estimates is being evaluated. These findings will provide a framework for predicting disease risk in humans exposed to other types of respirable particles and fibers for which we have rodent bioassay data but insufficient epidemiological data. This project is expected to provide a scientific basis for future NIOSH recommendations on occupational exposures to particles and fibers.
The long-term objective of this research is to provide an improved scientific basis for quantitative risk assessment of occupational exposure to respirable particles and fibers. The specific aims are to: (1) develop biologically-based dosimetry models to describe the clearance and retention kinetics of respirable particles and fibers in the lungs of animals and humans; (2) describe the dose-response relationships in each species, for both nonmalignant and malignant diseases; (3) predict disease risks in humans with working lifetime exposures; and (4) evaluate concordance of risk estimates across species. The overall impact of this project will be to enhance our understanding of key factors in the development of particle- and fiber-related lung diseases, and to use this information in risk assessment and disease prevention strategies for occupational exposure to respirable particles and fibers.
For particles, we are evaluating our previously-developed human lung dosimetry model in U.S. and U.K. coal miners (exposed to coal and quartz) for its applicability to other types of particles. Results show that coal miners' lung burdens may be under-predicted using existing lung models developed for radioactive particles. A research contract was initiated in late FY01 to obtain available exposure and lung burden data in farmers and other workers exposed to particulates, including at low concentrations. Data collection and compilation began in FY02-03, and was completed in FY05. In FY05 we began follow-up analyses to develop a job exposure matrix for farmers, which is expected to be completed in FY08. In FY09, we plan to begin testing the various model structures to investigate the bio-kinetic factors influencing particle retention in human lungs over a range of exposures and particle types. This study will contribute to our understanding of lung burdens and responses in humans based on our previously-published studies, and will be useful in risk assessment for respirable particles.
For fibers, investigations are underway to describe exposure, dose, and response relationships using existing data in animals and humans. Both lung dosimetry and biologically-based dose-response models are being used for this study. Research contracts were initiated in late FY01 to obtain transmission electron microscopy (TEM) analyses of NIOSH archived fiber samples (chrysotile asbestos), develop a revised job-exposure matrix (JEM) using the more detailed fiber dimension data, and update the mortality follow-up of this cohort. A TEM protocol was developed to balance both data quality needs for the study and cost constraints and pilot analyses were performed in FY02; the full data analyses began in FY03 and were completed in early FY05. These TEM data were being used to construct a job-exposure matrix based on bivariate fiber size data and develop various fiber dose metrics for use in epidemiological studies, biomathematical modeling, and risk assessment. The JEM was completed in FY05, and the epidemiology study was completed in FY07. Two papers on this work were published in FY08. These research findings may help to resolve discrepancies in the risk estimates from epidemiological studies of workers exposed to chrysotile in different occupations.
The primary objective of this project is to increase the understanding of the risks of occupational exposures to particulates and fibers. A better understanding of what characteristics of particles and fibers increase their toxicity will lead to more informed recommendations for controlling particularly hazardous exposures. One example of how this would work is the increased understanding of how the size and surface area of particles change their potential health effects. These data and mechanistic information are used in risk assessment of particulates.
The objective of this project is to provide an improved scientific basis for assessing the risk of occupational lung diseases among workers exposed to various types of respirable particles or fibers. Workers in mining, construction, agriculture, manufacturing and transportation may benefit from this research. In this research, existing data in both humans and animals for a given particle or fiber type are evaluated using biological and statistical models. The kinetic and biological factors influencing dose and disease processes are evaluated, as well as the concordance of risk estimates across species. These findings provide a basis for assessing the human health risk of exposure to various types of particles or fibers for which exposure-response data are available in animals, but not in humans. This research will be useful to NIOSH in developing occupational health recommendations, and to workers through the implementation of these recommendations. This project supports the NORA research priority area of risk assessment methods development. This project contributes to the following sectors:
As a risk assessment methods project, this work would apply to cancer risk assessments conducted for any hazard across all sectors.
Manufacturing (50%) – Strategic Goal 5: Reduce the number of respiratory conditions and diseases due to exposures in the manufacturing sector; and Strategic Goal 6: Reduce the prevalence of cancer due to exposures in the manufacturing sector. Mining (50%) – Strategic Goal 1: Reduce respiratory diseases in miners by reducing health hazards in the workplace associated with coal worker pneumoconiosis, silicosis, and diesel emissions. This project also contributes to these Cross-Sector Programs: Respiratory Diseases (50%) -- Strategic Goal 1: Prevent and reduce work-related airways diseases; Strategic Goal 2: Prevent and reduce work-related interstitial lung diseases; and Strategic Goal 4: Prevent and reduce work-related respiratory malignancies. Cancer, Reproductive, and Cardiovascular Diseases (50%) -- Strategic Goal 1: Reduce the incidence of work-related cancer. Nanotechnology (25%): Strategic Goal 1: Determine if nanoparticles and nanomaterials pose risks for work-related injuries and illnesses. Specifically, this project supports Output Goal 1.1.5 for risk assessment methods and IG4 Risk assessment.
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