Lung dosimetry and risk assessment for nanoparticles: use of in vitro and in vivo data to extend current models in rats and humans.
Kuempel-ED; Tran-CL; Castranova-V; Bailer-AJ
Frontiers in Aerosol Dosimetry Research: Proceedings of a Conference, October 24-25, 2005, Irvine, California. Phalen RF, Oldham MJ, Akhavan SW, Hoover MD, Asotra K, eds., Irvine, CA: Air Pollution Health Effects Laboratory, University of California, 2006 Jun; :4-52
Risk assessment of nanomaterials is a critical need in occupational safety and health. Human data are limited on exposure-response relationships to nanoparticles in the workplace, but quantitative data are available from a number of studies in rats. These studies have shown a consistent relationship between the particle surface area lung dose of respirable particles, including nanoparticles, and pulmonary inflammation and other responses. To use these data in risk assessment, a scientifically reasonable approach for extrapolating the rodent data to humans is required, including adjustment for species differences in the relationship between airborne exposures and internal dose. Lung dosimetry models provide a biologically-based approach to extrapolating internal doses (e.g., those associated with a given risk of disease) in animals to humans. However, current mass-based lung dosimetry models do not account for recently observed differences in the clearance and translocation of particles by size and composition. We describe the use of human lung dosimetry models in a risk assessment framework for inhaled particles. Statistical models are used to describe the dose-response relationships in rats and estimate disease risks associated with given particle doses. Human lung dosimetry models are used to estimate the exposures associated with the human-equivalent doses from the rat studies. Examples are provided using rat data for particles of low or high toxicity, and fine or ultrafine sizes. We also describe ongoing research to provide in vivo and in vitro data to fill gaps in the current lung dosimetry models such as size-specific particle clearance or translocation rates, and provide a basis for extrapolating these parameters to the human models when human data are lacking. These updated models will provide estimates of the retained particle dose by size and composition in the lungs and other organs, and therefore improve risk assessment of occupational exposure to nanoparticles.
Dosimetry; Lung; Models; Animals; Animal-studies; Risk-analysis; Occupational-exposure; Laboratory-animals; Quantitative-analysis; Dose-response; Chronic-exposure; Lung-cancer; Cancer; Lung-burden; Pulmonary-system-disorders; Nanotechnology
Phalen-RF; Oldham-MJ; Akhavan-SW; Hoover-MD; Asotra-K
Research Tools and Approaches: Risk Assessment Methods
Frontiers in Aerosol Dosimetry Research: Proceedings of a Conference, October 24-25, 2005, Irvine, California