Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Nov;119(11):1539-46.
doi: 10.1289/ehp.1103750. Epub 2011 Jul 25.

Informing selection of nanomaterial concentrations for ToxCast in vitro testing based on occupational exposure potential

Sumit Gangwal  1 , James S Brown, Amy Wang, Keith A Houck, David J Dix, Robert J Kavlock, Elaine A Cohen Hubal
Affiliations

Informing selection of nanomaterial concentrations for ToxCast in vitro testing based on occupational exposure potential

Sumit Gangwal et al. Environ Health Perspect. 2011 Nov.

Abstract

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™ program. Here, we provide testing concentrations for carbon nanotubes (CNTs) and titanium dioxide (TiO2) 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 TiO2 NPs 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.

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.

PubMed Disclaimer

Conflict of interest statement

The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the U.S. EPA. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

The authors declare they have no actual or potential competing financial interests.

Figures

Figure 1
Figure 1
General approach for recommending in vitro testing levels, considering exposure to NMs from occupational-setting indoor air via the inhalation route resulting in respiratory tract uptake. Estimated exposure potential is converted to levels for NM testing in HTS cellular assays.
Figure 2
Figure 2
MPPD model results of alveolar mass retained per alveolar surface area per inputted aerosol concentration versus particle diameter in human lungs for (A) TiO2 and Ag NPs with exposure durations of 45 years (full working lifetime) and 24 hr, and (B) CNTs with aspect ratios of 167, 10, 4, and 2 after 45 years of exposure. Both A and B are based on a light exercise breathing pattern. The curves are to guide the eye.
See this image and copyright information in PMC

Comment in

  • Nanotoxicology: in vitro-in vivo dosimetry.
    Oberdörster G. Oberdörster G. Environ Health Perspect. 2012 Jan;120(1):A13; author reply A13. doi: 10.1289/ehp.1104320. Environ Health Perspect. 2012. PMID: 22214547 Free PMC article. No abstract available.

References

    1. Anjilvel S, Asgharian B. A multiple-path model of particle deposition in the rat lung. Fundam Appl Toxicol. 1995;28(1):41–50. - PubMed
    1. Asgharian B, Hofman W, Bergmann R. Particle deposition in a multiple-path model of the human lung. Aerosol Sci Technol. 2001;34(4):332–339.
    1. Asgharian B, Price OT. Deposition of ultrafine (NANO) particles in the human lung. Inhal Toxicol. 2007;19:1045–1054. - PubMed
    1. Baron PA, Deye GJ, Chen BT, Schwegler-Berry DE, Shvedova AA, Castranova V. Aerosolization of single-walled carbon nanotubes for an inhalation study. Inhal Toxicol. 2008;20(8):751–760. - PubMed
    1. Bello D, Hart AJ, Ahn K, Hallock M, Yamamoto N, Garcia EJ, et al. Particle exposure levels during CVD growth and subsequent handling of vertically-aligned carbon nanotube films. Carbon. 2008;46(6):974–977.

LinkOut - more resources