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Informing Selection of Nanomaterial Concentrations for ToxCast In Vitro Testing based on Occupational Exposure Potential
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 based on Occupational Exposure Potential. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 119(11):1539-1546, (2011).
Impact/Purpose:
Our goal is to use estimates of lung deposition following occupational exposure to nanomaterials to recommend in vitro testing concentrations for the U.S. Environmental Protection Agency’s ToxCastTM program. We provide testing concentrations for carbon nanotubes (CNTs), titanium dioxide (TiO2) and silver (Ag) nanoparticles.
Description:
Little justification is generally provided for selection of in vitro assay testing concentrations for engineered nanomaterials (ENMs). Selection of concentration levels for hazard evaluation based on real-world exposure scenarios is desirable. We reviewed published ENM concentrations measured in air in manufacturing and R&D labs to identify input levels for estimating ENM mass retained in the human lung using the Multiple-Path Particle Dosimetry (MPPD) model. Model input parameters were individually varied to estimate alveolar mass retained for different particle sizes (5-1000 nm), aerosol concentrations (0.1, 1 mg/m3), aspect ratios (2, 4, 10, 167), and exposure durations (24 hours and a working lifetime). The calculated lung surface concentrations were then converted to in vitro solution concentrations. Modeled alveolar mass retained after 24 hours is most affected by activity level and aerosol concentration. Alveolar retention for Ag and TiO2 nanoparticles and CNTs for a working lifetime (45 years) exposure duration is similar to high-end concentrations (~ 30-400 μg/mL) typical of in vitro testing reported in the literature. Analyses performed are generally applicable to provide ENM testing concentrations for in vitro hazard screening studies though further research is needed to improve the approach. Understanding the relationship between potential real-world exposures and in vitro test concentrations will facilitate interpretation of toxicological results.
