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Informing Selection of Nanomaterial Concentrations for ToxCast In Vitro Testing using the Multiple-Path Particle Dosimetry Model - 3rd Annual International Conference on the Environmental Implications of NanoTechnology (ICEIN) & EPA Nano Grantees Meeting (2011)
Citation:
GANGWAL, S., JAMES S. BROWN, A. WANG, K. A. HOUCK, D. J. DIX, R. J. KAVLOCK, AND E. A. COHEN-HUBAL. Informing Selection of Nanomaterial Concentrations for ToxCast In Vitro Testing using the Multiple-Path Particle Dosimetry Model - 3rd Annual International Conference on the Environmental Implications of NanoTechnology (ICEIN) & EPA Nano Grantees Meeting (2011). Presented at 3rd Annual International Conference on the Environmental Implications of NanoTechnology (ICEIN) & EPA Nano Grantees Meeting, Durham, NC, May 09 - 11, 2011.
Impact/Purpose:
Nanomaterial concentrations in air (particle mass or count per air volume) are being measured in manufacturing and R&D lab settings. We reviewed nanomaterial levels reported across facility types for different nanomaterial classes. Using particle number concentration data from these studies, we calculated nanomaterial mass retained in the trachobronchial and alveolar regions of the human lung using the open-source Multiple-Path Particle Dosimetry (MPPD) model. Analyses performed and results obtained here are generally applicable to inform the design of nanomaterial in vitro hazard screening studies.
Description:
Currently, little justification is provided for nanomaterial testing concentrations in in vitro assays. The in vitro concentrations typically used may be higher than those experienced by exposed humans. Selection of concentration levels for hazard evaluation based on real-world exposure scenarios is desirable. Nanomaterial concentrations in air (particle mass or count per air volume) are being measured in manufacturing and R&D lab settings. We reviewed nanomaterial levels reported across facility types for different nanomaterial classes. Using particle number concentration data from these studies, we calculated nanomaterial mass retained in the trachobronchial and alveolar regions of the human lung using the open-source Multiple-Path Particle Dosimetry (MPPD) model. These estimates of inhalation dosimetry were performed for carbon nanotubes (CNTs), titanium dioxide (TiO2) and silver (Ag) nanoparticles. The key model input parameters that affect the alveolar mass retained after 24 hours of nanoparticle exposure were particle size and size geometric standard deviation, aspect ratio, breathing conditions (resting, light or heavy exercise), and aerosol concentration. These key parameters were varied to further calculate alveolar mass retained per alveolar surface area (g/cm2) for different particle sizes (ranging from 5 to 100 nm), aerosol concentrations (0.1 and 1 mg/m3), and exposure times (24 hours and a full working lifetime of 45 years at 8 hours per day, 5 days per week of aerosol inhalation). The alveolar mass retained per surface area for Ag and TiO2 nanoparticles and CNTs for a full working lifetime exposure duration was similar to the high-end concentrations (~ 30-400 g/mL) typical of in vitro testing. Analyses performed and results obtained here are generally applicable to inform the design of nanomaterial in vitro hazard screening studies. [This abstract may not necessarily reflect U.S. EPA policy.]