Grantee Research Project Results
2015 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 , Georgopoulos, Panos G. , Di Giulio, Richard T. , Lioy, Paul J. , Isukapalli, Sastry S. , Kipen, Howard , Chung, Kian Fan , Garfunkel, Eric , Lee, Ki-Bum , Mainelis, Gediminas , Porter, Alexandra , Ryan, Mary P. , Schwander, Stephan K. , Tetley, Teresa D
Current 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 , 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: April 1, 2015 through March 31,2016
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:
The overall objective of the RAMNUC project is to assess physicochemical and toxicological properties of manufactured nanoparticles (MNPs) at the point of exposure for both humans and aquatic animals in comparison to those properties of the MNPs at the source (synthesized in the laboratory or acquired commercially). The differences between the source and the point of exposure may have significant consequences with respect to MNPs’ bioavailability, alterations of immunity, induction of oxidative stress, inflammation, disease processes, and other toxicity measures.
Approach: Exposures to MNPs released from the use of consumer products are characterized using laboratory simulation studies. Population exposure to MNPs is predicted using mathematical modeling. The intracellular and extracellular bioavailability and toxicity of the selected MNPs, as synthesized and as incorporated in or released from consumer products, are assessed by using both in vitro and in vivo experiments. Tested MNPs are well characterized for their physical (e.g., size, shape, state of agglomeration/aggregation) and chemical properties (e.g., composition, functionalization, and surface chemistry). Experimental data are modeled toward generalizable risk assessment using a source-to-dose-to-health effects modeling system.
Progress Summary:
The RAMNUC project has had several successes since its initiation, including the following:
1. It is expected research results will be used to guide environmental health policy with regard to NMPs in consumer products. The first step is to have the research findings published in peer-reviewed journals. The RAMNUC project has published fifteen papers since 2012. Eight additional manuscripts are in preparation and one in review. These manuscripts have been published in high impact journals.
2. Collaboration with the UK and US partners has been essential for the overall success of the project. Since the initiation of the project, the RAMNUC team has demonstrated flexibility with monthly conference calls as it is sometimes required to change the time or day of the call. RAMNUC team members from both the US and the UK side send monthly detailed reports or slides to the project coordinator and are presented during the monthly calls. These presentations generate excellent ideas for further analysis and experimentation. Collaborators also send updates regarding manuscript submissions and progress. Similarly, discussions may continue after the RAMNUC calls or additional calls are scheduled for a smaller group to further discuss ideas and resolve problems revealed during the call. The Coordinator serves as a point of contact for investigators to obtain additional data files as necessary. The complimentary expertise from the US and the UK side played a key role not only in designing a novel project but also in gauging us to use the most advanced and effective experimental approaches.
3. All studies involving blood collected from human subjects to obtain human monocyte have been completed. IRB protocol approvals pertaining to the project are stored at Rutgers University and Duke University. All in vivo experiments conducted at Imperial College London, the solely institution approved for animal studies, have been finalized. Documentation regarding IACUC approvals and protocols are saved at Imperial College and Duke University and will be kept for future reference. All studies involving animals were conducted only at Imperial College London.
On May 2015, RAMNUC investigators from Rutgers University and Imperial College came together for a one-day workshop at Duke University to discuss a work plan for experiments and publications for the final year of the project. Collaborators shared their most recent findings via PowerPoint presentations which generated productive discussions as well as new approaches for data analysis and future work. The workshop also led to discussion regarding potential future collaborations in the field.
Briefly, our work on consumer products has generated the following findings that have implications for public health and can be used to inform policy matters.
1. We investigated the effect of addition of cerium oxide (as Envirox) to diesel at 0x, 0.1x, 1.0x and 10.0x (times) the manufacturer’s recommended level on the physicochemical properties of the diesel exhaust particles (DEP), and on their bioreactivity with human lung cells from the respiratory unit, where a significant proportion of inhaled nanoparticles deposit. Interestingly, we found that DEP generated from diesel with Envirox is less inflammatory compared to DEP released without the addition of Envirox or with lower concentration of Envirox. The changes in inflammatory response can be explained by the changes in several physicochemical properties.
2. In studies of consumer spray products containing silver and zinc nanoparticles, we discovered that the bioreactivity of the product varied depends on the type of particle and the medium (i.e., carrier solution). Neither the silver particles, nor the medium of Mesosilver was toxic to respiratory lung cells in vitro. In contrast, for Nanofix, which also contained silver particles, the silver particles were toxic alone, as was high concentration of the medium alone, and the mixture was extremely toxic. Therazinc was also found to be very toxic, largely due to the medium, but also at high particle concentrations. Conversely, Dermazinc the whole product was toxic; but it was the particles that were most toxic, whereas the medium was toxic only at high concentrations. These studies of sprays indicate that even if these sprays are used for other purposes (e.g., cleaning and skin conditions) unintended inhalation could have adverse health effects as we show in our mouse models exposed to these products.
Results from the RAMNUC project help our limited understanding of toxicity and bio-reactivity of the MNPs contained in consumer products, in relation to specific physicochemical properties of MNPs. The RAMNUC project uses a novel human exposure simulation study producing realistic estimates of MNPs exposures to consumers. The MNPs under study include emissions released from a diesel engine that uses a nano-ceria based fuel additive and aerosols released from consumer spray products containing nano silver or nano zinc oxide.
Future Activities:
Data generated are being integrated into the mechanism -based computational modules of two existing source-to-exposure-to-dose-to-effects modeling systems, allowing for rational extrapolation and generalization in MNPs risk assessment. The findings contribute to our very limited knowledge about health risks associated with the use of nanotechnology based consumer products.
Journal Articles on this Report : 27 Displayed | Download in RIS Format
| Other project views: | All 47 publications | 28 publications in selected types | All 28 journal articles |
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Calderon L, Han T, McGilvery CM, Yang L, Subramaniam P, Lee K-B, Schwander S, Tetley TS, Georgopoulos P, Ryan M, Porter AE, Smith R, Chung KF, Lioy PJ, Zhang J, Mainelis G. Release of airborne particles and Ag and Zn compounds from nanotechnology-enabled consumer sprays: Implications for inhalation exposure. Atmospheric Environment. 2017;155:85-96. |
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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. |
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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. |
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Chen S, Goode AE, Skepper JN, Thorley AJ, Seiffert JM, Chung KF, Tetley TD, Shaffer MS, Ryan MP, Porter AE. Avoiding artefacts during electron microscopy of silver nanomaterials exposed to biological environments. Journal of Microscopy 2015;261(2):157-166. |
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Cole TB, Fisher JC, Burbacher TM, Costa LG, Furlong CE. Neurobehavioral assessment of mice following repeated postnatal exposure to chlorpyrifos-oxon. Neurotoxicology and Teratology. 2012;34(3):311-22. |
R834693 (2015) R834514 (Final) R834514C004 (Final) |
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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. |
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Lopez-Heras M, Theodorou IG, Leo BF, Ryan MP, Porter AE. Towards understanding the antibacterial activity of Ag nanoparticles: electron microscopy in the analysis of the materials-biology interface in the lung. Environmental Science: Nano 2015;2(4):312-326. |
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Mukherjee D, Leo BF, Royce SF, Porter AE, Ryan MP, Schwander S, Chung KF, Tetley TD, Zhang J, Georgopoulos PG. Modeling physiochemical interactions affecting in vitro cellular dosimetry of engineered nanomaterials: application to nanosilver. Journal of Nanoparticle Research 2014;16(10):2616 (29 pp.). |
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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. |
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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.). |
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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. |
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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. |
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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.). |
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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.). |
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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.). |
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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) |
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Theodorou IG, Ryan MP, Tetley TD, Porter AE. Inhalation of silver nanomaterials--seeing the risks. International Journal of Molecular Sciences 2014;15(12):23936-23974. |
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Theodorou IG, Botelho D, Schwander S, Zhang J, Chung KF, Tetley TD, Shaffer MS, Gow A, Ryan MP, Porter AE. Static and dynamic microscopy of the chemical stability and aggregation state of silver nanowires in components of murine pulmonary surfactant. Environmental Science & Technology 2015; 49(13):8048-8056. |
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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. |
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Zhang J, Lee K-B, He L, Seiffert J, Subramaniam P, Yang L, Chen S, Maguire P, Mainelis G, Schwander S, Tetley T, Porter, A, Ryan M, Shaffer M, Hu S, Gong J, Chung KF. Effects of a nanoceria fuel additive on physicochemical properties of diesel exhaust particles. Environmental Science: Processes and Impacts 2016;18(10):1333-1342. |
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Sarkar S, Song Y, Sarkar S, Kipen HM, Laumbach RJ, Zhang J, Strickland PA, Gardner CR, Schwander S. Suppression of the NF-κB pathway by diesel exhaust particles impairs human antimycobacterial immunity. The Journal of Immunology. 2012;188(6):2778-93 |
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Mukherjee D, Royce SG, Sarkar S, Thorley A, Schwander S, Ryan MP, Porter AE, Chung KF, Tetley TD, Zhang J, Georgopoulos PG. Modeling in vitro cellular responses to silver nanoparticles. Journal of Toxicology 2014;2014:852890 (13 pp.). |
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Mukherjee D, Porter, A, Ryan M, Schwander S, Chung KF, Tetley T, Zhang J, Georgopoulos P. Modeling in vivo interactions of engineered nanoparticles in the pulmonary alveolar lining fluid. Nanomaterials 2015;5(3):1223-1249. |
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Theodorou IG, Ruenraroengsak P, Gow A, Schwander S, Zhang JJ, Chung KF, Tetley TD, Ryan MP, Porter AE. Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells. Nanotoxicology 2016;10(9):1351-1362. |
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Chung KF, Seiffert J, Chen S, Theodorou I, Goode A, Leo BF, McGilvery C, Hussain F, Wiegman C, Rossios C, Zhu J, Gong J, Tariq F, Yufit V, Monteith A, Hashimoto T, Skepper J, Ryan M, Zhang J, Tetley T, Porter A. Inactivation, clearance and functional effects of lung-instilled short and long silver nanowires in rat. ACS Nano 2017;11(3):2652-2664. |
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Mukherjee D, Botelho D, Gow A, Zhang J, Georgopoulos PG. Computational multiscale toxicodynamic modeling of silver and carbon nanoparticle effects on mouse lung function. 2013, PLOS One, 8(12):e80917. |
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Sweeney S, Theodorou IG, Zambianchi M, Chen S, Gow A, Schwander S, Zhang J, Chung KF, Shaffer MS, Ryan MP, Porter AE, Tetley TD. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions:contrasting bioreactivity with human alveolar type-I and type-II epithelial cells. Nanoscale, 2015 Jun 4;7(23):10398-409. |
R834693 (2015) |
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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
- 2014 Progress Report
- 2013 Progress Report
- 2012 Progress Report
- 2011 Progress Report
- Original Abstract
28 journal articles for this project