Grantee Research Project Results
2014 Progress Report: Risk Assessment for Manufactured Nanoparticles Used in Consumer Products (RAMNUC)
EPA Grant Number: R834693Title: Risk Assessment for Manufactured Nanoparticles Used in Consumer Products (RAMNUC)
Investigators: Zhang, Junfeng , Tetley, Teresa D , Chung, Kian Fan , Georgopoulos, Panos G. , Lioy, Paul J. , Schwander, Stephan K. , Ryan, Mary P. , Isukapalli, Sastry S. , Di Giulio, Richard T. , Porter, Alexandra , Garfunkel, Eric , Mainelis, Gediminas , Kipen, Howard , Lee, Ki-Bum
Institution: University of Medicine and Dentistry of New Jersey , Imperial College , Duke University
Current Institution: University of Medicine and Dentistry of New Jersey , Duke University , Imperial College
EPA Project Officer: Aja, Hayley
Project Period: April 1, 2011 through June 30, 2014 (Extended to June 30, 2016)
Project Period Covered by this Report: July 1, 2013 through June 30,2014
Project Amount: $1,999,995
RFA: Environmental Behavior, Bioavailability and Effects of Manufactured Nanomaterials - Joint US – UK Research Program (2009) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability
Objective:
Progress Summary:
Aim 1 (Risk Assessment Framework):
- Modules for estimating realistic environmental and occupational exposures to MNPs are being developed: (a) modules for environmental levels of CeO2 nanoparticles used as a fuel additive have been developed by evaluating and applying this framework in complementary research efforts, and (b) modules for environmental levels of zinc oxide (ZnO) are being developed as part of Aim 1.
- Modules for population exposures to CeO2 nanoparticles (used as a fuel additive) have been developed incorporating exposure simulation studies (Aim 4) to support risk assessments of the MNP. These modules have been coupled with the existing human airway dosimetry model, Multiple-Path Particle Dosimetry Model (MPPD v2.11), to characterize the population-wide distributions of alveolar, tracheobronchial and pharyngeal depositions considering the particle size measurements of DEP (Aim 4) and the age/gender distribution of the CONUS (contiguous U.S.) population.
- Modules for estimating population exposures to silver nanoparticles from consumer usage of nanospray products and from ambient sources have undergone further refinement and development in Year 3 to: (a) expand the calculation of intake fractions to include exposures to silver nanoparticles in non-residential buildings; (b) incorporate county-level consumer expenditure data on personal care and cleaning products into the exposure modules of silver nanoparticles for the CONUS population; (c) benchmark the population-wide distributional estimates of intake values against individual-based estimates from regulatory European consumer exposure models; and (d) perform preliminary risk-relevant calculations by comparing estimated population-wide intake values against published human indicative no-effect levels (INEL).
Aim 2 (Nanoparticle Synthesis and Characterization):
Aim 3 (Exposure Simulation Studies):
Effect of nanoparticles in consumer products on human alveolar cells in vitro. A number of products were originally chosen for characterization. Subsequently, four products, two silver containing and two zinc containing were chosen for in vitro studies of TT1 cells. Each product was studied as the whole product, the particle-containing fraction and non-particle containing fraction (following the establishment of a suitable protocol to do this; these fractions currently are being further characterized at Rutgers University). We have performed some preliminary cytotoxicity studies using a range of dilutions from the original product. The actual concentrations of nanoparticles and other reagents will be determined following full characterization.
None of the Mesosilver fractions had an effect on TT1 cell viability at 24 hours, at original product dilution ranges of 1/100 to 1/10. Neither were there any changes in pro-inflammatory cytokine release using these Mesosilver fractions. In contrast, Nanofix was extremely cytotoxic to TT-1 cells at dilutions from 1/100 to 1/10. This effect was partly due to the nanoparticles and partly due to other components in the suspension medium of the product. There were significantly increased levels of IL-6 and IL-8 production at all dose ranges observed in the nanoparticle-containing and particle-free fractions of Nanofix.
Cytotoxicity and bioreactivity of DEP in peripheral blood mononuclear cells (PBMC). Metabolic activity of cells (proportional to the number of viable cells) was evaluated by MTS assay (Figure 1). PBMC from healthy donors exposed to no particles served as control. No significant effect on the viability of PBMC was observed at any of the dosages used (0, 1, 10 μg/mL) by MTS assay.
To assess bioreactivity of DEPs in PBMC, frequencies of cytokine (IL-1ß and TNF-α [IFN-γ and IL-6 not shown])-producing cells as well as IL1b, TNFa, IL6 and IL8 mRNA expression were assessed in PBMC by ELISPOT assays and qRT-PCR, respectively (Figure 2). We found that PBMC in vitro exposure to all the DEPs (resulting from diesel with varying amount of Envirox added) resulted in very limited bioreactivity with the exception of that induced by the DEP emitted from diesel containing 0.1x Envirox. We are investigating the reasons why DEP from 0.1x Envirox fuel showed significantly higher bioreactivity compared to the DEP from diesel containing other amount of Envirox.
Effects of consumer product (Mesosilver, Nanofix, Derma Zinc, Thera Zinc) -derived Ag and Zn nanoparticles and suspension fractions thereof (whole product, NP-free and Concentrated NP fractions) on toxicity and IL-1β and TNF-α expression (ELISPOT assays) in human PBMC. In toxicity studies, PBMC were exposed to different fractions of Meso Silver (upper panel) and Nanofix Silver (lower panel) at 1:10, 1:20, 1:40, 1:80 dilution for 24 hours (at 37ºC in a humidified 5% CO2 environment). PBMC cultured in complete culture media without NP exposure (none) were used as unexposed controls. Cell viability was measured by MTS assay. The results are summarized in Table 1. Because of the extreme toxic nature of some of the products, we currently are testing their bioreactivity with further dilutions (50-400 fold).
- Incorporated additional measurements of particle size distributions of consumer nanospray products (exposure simulation studies of Aim 3) into the population exposure modules of nAg.
- Parameterized particle size distributions of DEP for the exposure modules of CeO2 according to data from Aim 4.
Future Activities:
Journal Articles on this Report : 12 Displayed | Download in RIS Format
Other project views: | All 47 publications | 28 publications in selected types | All 28 journal articles |
---|
Type | Citation | ||
---|---|---|---|
|
Chen S, Theodorou IG, Goode AE, Gow A, Schwander S, Zhang JJ, Chung KF, Tetley TD, Shaffer MS, Ryan MP, Porter AE. High-resolution analytical electron microscopy reveals cell culture media-induced changes to the chemistry of silver nanowires. Environmental Science & Technology 2013;47(23):13813-13821. |
R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit Exit |
|
Chen S, Goode AE, Sweeney S, Theodorou IG, Thorley AJ, Ruenraroengsak P, Chang Y, Gow A, Schwander S, Skepper J, Zhang JJ, Shaffer MS, Chung KF, Tetley TD, Ryan MP, Porter AE. Sulfidation of silver nanowires inside human alveolar epithelial cells: a potential detoxification mechanism. Nanoscale 2013;5(20):9839-9847. |
R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit Exit |
|
Leo BF, Chen S, Kyo Y, Herpoldt KL, Terrill NJ, Dunlop IE, McPhail DS, Shaffer MS, Schwander S, Gow A, Zhang J, Chung KF, Tetley TD, Porter AE, Ryan MP. The stability of silver nanoparticles in a model of pulmonary surfactant. Environmental Science & Technology 2013;47(19):11232-11240. |
R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit |
|
Nazarenko Y, Zhen H, Han T, Lioy PJ, Mainelis G. Potential for inhalation exposure to engineered nanoparticles from nanotechnology-based cosmetic powders. Environmental Health Perspectives 2012;120(6):885-892. |
R834693 (2011) R834693 (2012) R834693 (2013) R834693 (2014) R834693 (2015) R834693 (Final) |
|
|
Nazarenko Y, Zhen H, Han T, Lioy PJ, Mainelis G. Nanomaterial inhalation exposure from nanotechnology-based cosmetic powders: a quantitative assessment. Journal of Nanoparticle Research 2012;14(11):1229 (14 pp.). |
R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit |
|
Nazarenko Y, Lioy PJ, Mainelis G. Quantitative assessment of inhalation exposure and deposited dose of aerosol from nanotechnology-based consumer sprays. Environmental Science: Nano 2014;1(2):161-171. |
R834693 (2013) R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit |
|
Royce SG, Mukherjee D, Cai T, Xu SS, Alexander JA, Mi Z, Calderon L, Mainelis G, Lee K, Lioy PJ, Tetley TD, Chung KF, Zhang J, Georgopoulos PG. Modeling population exposures to silver nanoparticles present in consumer products. Journal of Nanoparticle Research 2014;16(11):2724. |
R834693 (2013) R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit |
|
Sarkar S, Zhang L, Subramaniam P, Lee KB, Garfunkel E, Strickland PA, Mainelis G, Lioy PJ, Tetley TD, Chung KF, Zhang J, Ryan M, Porter A, Schwander S. Variability in bioreactivity linked to changes in size and zeta potential of diesel exhaust particles in human immune cells. PLoS ONE 2014;9(5):e97304 (12 pp.). |
R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit Exit |
|
Seiffert J, Hussain F, Wiegman C, Li F, Bey L, Baker W, Porter A, Ryan MP, Chang Y, Gow A, Zhang J, Zhu J, Tetley TD, Chung KF. Pulmonary toxicity of instilled silver nanoparticles: influence of size, coating and rat strain. PLOS ONE 2015;10(3):e0119726 (17 pp.). |
R834693 (2013) R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit Exit |
|
Seiffert J, Buckley A, Leo B, Martin NG, Zhu J, Dai R, Hussain F, Guo C, Warren J, Hodgson A, Gong J, Ryan MP, Zhang JJ, Porter A, Tetley TD, Gow A, Smith R, Chung KF. Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague-Dawley rats. Respiratory Research 2016;17(1):85 (15 pp.). |
R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit Exit |
|
Subramaniam P, Lee SJ, Shah S, Patel S, Starovoytov V, Lee K-B. Generation of a library of non-toxic quantum dots for cellular imaging and siRNA delivery. Advanced Materials 2012;24(29):4014-4019. |
R834693 (2011) R834693 (2012) R834693 (2013) R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit |
|
Zhang J, Nazarenko Y, Zhang L, Calderon L, Lee KB, Garfunkel E, Schwander S, Tetley TD, Chung KF, Porter AE, Ryan M, Kipen H, Lioy PJ, Mainelis G. Impacts of a nanosized ceria additive on diesel engine emissions of particulate and gaseous pollutants. Environmental Science & Technology 2013;47(22):13077-13085. |
R834693 (2013) R834693 (2014) R834693 (2015) R834693 (Final) |
Exit Exit |
Supplemental Keywords:
Consumer products, manufactured nanoparticles, diesel exhaust particles, inhalation exposureProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final Report
- 2015 Progress Report
- 2013 Progress Report
- 2012 Progress Report
- 2011 Progress Report
- Original Abstract
28 journal articles for this project