Academic journal article Environmental Health Perspectives

Informing Selection of Nanomaterial Concentrations for Toxcast in Vitro Testing Based on Occupational Exposure Potential

Academic journal article Environmental Health Perspectives

Informing Selection of Nanomaterial Concentrations for Toxcast in Vitro Testing Based on Occupational Exposure Potential

Article excerpt

BACKGROUND: 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,

OBJECTIVES: Our goal was to use estimates of lung deposition after occupational exposure to nanomaterials to recommend in vitro testing concentrations for the U.S. Environmental Protection Agency's ToxCast [TM] program. Here, we provide testing concentrations for carbon nanotubes (CNTs) and titanium dioxide ([TiO.sub.2]) and silver (Ag) nanoparticles (NPs).

METHODS: We reviewed published ENM concentrations measured in air in manufacturing and R&D (research and development) laboratories 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 (5-1,000 nm), aerosol concentrations (0.1 and 1 mg/m3), aspect ratios (2, 4, 10, and 167), and exposure durations (24 hr and a working lifetime). The calculated lung surface concentrations were then converted to in vitro solution concentrations.

RESULTS: Modeled alveolar mass retained after 24 hr is most affected by activity level and aerosol concentration. Alveolar retention for Ag and [TiO.sub.2] NPs and CNTs for a working-lifetime (45 years) exposure duration is similar to high-end concentrations (~ 30-400 [micro]g/mL) typical of in vitro testing reported in the literature.

CONCLUSIONS: Analyses performed are generally applicable for providing ENM testing concentrations for in vitro hazard screening studies, although 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.

Key WORDS: ExpoCast, human particle deposition and retention, in vitro nanomaterial concentration, multiple-path particle dosimetry (MPPD), occupational exposure, ToxCast. Environ Health Perspect 119:1539-1546 (2011). http://dx.doi.org/10.1289/ehp.1103750 [Online 25 July 2011]

Researchers evaluating toxicity and human exposure potential of engineered nano-materials (ENMs) are challenged by rapid development of novel materials for new applications as the nanotechnology industry drives forward. These materials can add significant value to industrial or consumer products. ENMs have one or more components with at least one dimension in the range of 1-1,000 nm. Components can include nano-particles (NPs), nanofibers and nanotubes, nanodots, nanostructured surfaces, or nano-composites. Carbon nanotubes (CNTs) and metal oxide NPs (two material types having the highest industrial production volumes) are used in plastics, catalysts, battery and fuel cell electrodes, solar cells, paints, coatings, etc. (Blaine et al. 2008). Nanoparticulate silver (Ag) has the greatest number of consumer product applications. Novel nanomaterial (NM) types continue to be synthesized based on the value they may add, often without evaluation of implications for human health, toxicity, environmental impact, or long-term sustainability. NMs, especially the ones made of metals, semiconductors, and various inorganic compounds, have the potential for post-use risks to humans and the environment (National Nanotechnology Initiative 2008). These concerns need to be examined and addressed before the widespread adoption of nanotechnologies (Oberdorster et al. 2005).

The U.S. Environmental Protection Agency (U.S. EPA) is beginning to evaluate exposure and hazard potential of NMs and prioritize them for further animal-based toxicological testing. Prioritization of NM classes and types for targeted testing is important in the early stages of NM development. Currently, only a small portion of the thousands of commonly used chemicals in the Toxic Substances Control Act (1976) inventory (U. …

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