Grantee Research Project Results
Predictive Toxicology Center for Organotypic Cultures and Assessment ofAOPs for Engineered Nanomaterials
EPA Grant Number: R835738Center: Center for Air, Climate, and Energy Solutions
Center Director: Robinson, Allen
Title: Predictive Toxicology Center for Organotypic Cultures and Assessment ofAOPs for Engineered Nanomaterials
Investigators: Faustman, Elaine , Griffith, William C. , Kavanagh, Terrance J , Altemeier, William , Kelly, Edward J. , Eaton, David , Gao, Xiaohu
Institution: University of Washington
EPA Project Officer: Callan, Richard
Project Period: December 1, 2014 through November 30, 2019 (Extended to November 30, 2020)
Project Amount: $6,000,000
RFA: Organotypic Culture Models for Predictive Toxicology Center (2013) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability
Objective:
The overall goal of this Center is to develop innovative organotypic culture systems to better evaluate the potential for cellular and organ toxicity following exposure to Engineered Nanomaterials (ENMs) within an adverse outcomes pathway (AOP) model. We have designed four organotypic culture projects that reflect complexity and function of lung, kidney, liver and testis. Our center will provide an academic research setting to further develop 3-D organotypic culture systems. We will accomplish this by integrating the extensive research currently occurring at the University of Washington on this topic with this new and exciting initiative from the EPA.
Approach:
We will illustrate the importance of organotypic culture application and our integrating models to assess our observations across species, organs, and lifestages. These models will help scientists and regulatory agencies answer the need for better, more informative and faster testing of emerging environmental contaminants in the context of the organ and organ systems. Our work will greatly increase the EPA’s ability to make informed regulatory decisions by targeting metals and metal based ENMs.
Rationale:
We will design 3D organotypic culture models for the Lung, Kidney, Liver and Testis using initial technologies from UW funded projects (Nanotoxicology Center, Center for Nanotechnology and our UH2 grant from NIH for microphysiological systems). Two of our systems will build off established microfluidic culture approaches (kidney and liver). For lung we have designed an air-liquid interface culture system using differentiated primary tracheal epithelial cells. For testis we have designed a co-culture system that has been proven to mimic testicular morphogenesis and function in vitro for over two weeks. Our Center will include technological innovations such as cell specific tagging (Ribotag) of transcriptomic responses and microfluidic applications that will be developed in one organotypic culture and then transferred to our other organ systems as validation and lessons learned evolve. Our cultures will use common markers of response at multiple levels of biological evaluation (molecular to cell and tissue level) to facilitate comparisons of responses to ENMs across organs and to inform our AOP models. Our project 5 will design a systems based approach for evaluating and testing AOP based hypotheses across Center organotypic culture, dose type of metal based ENM. Our AOP hypotheses includes evaluation of oxidative and inflammatory pathways, windows of susceptibility, and genetic evaluations of ENM responses after both acute as well as 14 day exposures within a toxicokinetic and dynamic driven risk assessment framework.
Journal Articles: 50 Displayed | Download in RIS Format
| Other center views: | All 150 publications | 50 publications in selected types | All 49 journal articles |
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Bajaj, P., Chowdhury SK, Yucha R, Kelly EJ and Xiao G. Emerging Kidney Models to Investigate Metabolism, Transport, and Toxicity of Drugs and Xenobiotics. Drug Metabolism and Disposition 2018: 46(11);1692-1702. |
R835738C001 (2018) R835738C002 (2018) |
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Cartwright MM, Schmuck SC, Corredor C, Wang B, Scoville DK, Chisholm CR, Wilkerson HW, Afsharinejad Z, Bammler TK, Posner JD, Shutthanandan V, Baer DR, Mitra S, Altemeier WA, Kavanagh TJ. The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis. Redox Biology 2016;9:264-275. |
R835738 (2016) R835738 (2017) R835738C001 (2016) |
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Chang S-Y, Weber EJ, Van Ness KP, Eaton DL, Kelly EJ. Liver and kidney on chips: microphysiological models to understand transporter function. Clinical Pharmacology & Therapeutics 2016;100(5):464-478. |
R835738 (2016) R835738 (2017) R835738C002 (2016) R835738C003 (2016) R835738C003 (2017) R835738C005 (2017) |
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Chang S-Y, Weber EJ, Sidorenko VS, Chapron A, Yeung CK, Gao C, Mao Q, Shen D, Wang J, Rosenquist TA, Dickman KG, Neumann T, Grollman AP, Kelly EJ, Himmelfarb J, Eaton DL. Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity. JCI Insight 2017;2(22):95978 (15 pp.). |
R835738 (2017) R835738C002 (2017) R835738C002 (2018) |
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Chang S-Y, Weber EJ, Sidorenko VS, Chapron A, Yeung CK, Gao C, Mao Q, Shen D, Wang J, Rosenquist TA, Dickman KG, Neumann T, Grollman AP, Kelly EJ, Himmelfarb J, Eaton DL. Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity. JCI Insight 2017;2(22):e95978 (15 pp.). |
R835738C003 (2017) R835738C005 (2017) |
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Chang S-Y, Weber EJ, Sidorenko VS, Chapron A, Yeung CK, Gao C, Mao Q, Shen D, Wang J, Rosenquist TA, Dickman KG, Neumann T, Grollman AP, Kelly EJ, Himmelfarb J, Eaton DL. Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity. JCI Insight 2017;2(22):95978 (15 pp.). |
R835738 (2017) R835738C002 (2017) R835738C002 (2018) |
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Chang S-Y, Voellinger JL, Van Ness KP, Chapron B, Shaffer RM, Neumann T, White CC, Kavanagh TJ, Kelly EJ, Eaton DL. Characterization of rat or human hepatocytes cultured in microphysiological systems (MPS) to identify hepatotoxicity. Toxicology In Vitro 2017;40:170-183. |
R835738 (2016) R835738 (2017) R835738C002 (2016) R835738C002 (2017) R835738C003 (2016) R835738C003 (2017) |
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Harris S, Hermsen SA, Yu X, Hong SW, Faustman EM. Comparison of toxicogenomic responses to phthalate ester exposure in an organotypic testis co-culture model and responses observed in vivo. Reproductive Toxicology 2015;58:149-159. |
R835738 (2016) R835738 (2017) R835738C004 (2015) R835738C004 (2017) R834514 (Final) R834514C003 (2015) R834514C003 (Final) |
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Harris S, Wegner S, Hong SW, Faustman EM. Phthalate metabolism and kinetics in an in vitro model of testis development. Toxicology in Vitro 2016;32:123-131. |
R835738 (2016) R835738 (2017) R835738C004 (2015) R835738C004 (2016) R835738C004 (2017) R833772 (2009) R834514 (Final) R834514C003 (Final) |
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Harris S, Shubin SP, Wegner S, Van Ness K, Green F, Hong SW, Faustman EM. The presence of macrophages and inflammatory responses in an in vitro testicular co-culture model of male reproductive development enhance relevance to in vivo conditions. Toxicology In Vitro 2016;36:210-215. |
R835738 (2016) R835738 (2017) R835738C004 (2016) R835738C004 (2017) R834514 (Final) R834514C003 (Final) |
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Kim YH, Jo MS, Kim JK, Shin JH, Baek JE, Park HS, An HJ, Lee JS, Kim BW, Kim HP, Ahn KH, Jeon KS, Oh SM, Lee JH, Workman T, Faustman EM, Yu IJ. Short-term inhalation study of graphene oxide nanoplates. Nanotoxicology 2018;12(3):224-238. |
R835738 (2017) R835738C001 (2018) R835738C004 (2018) R835738C005 (2018) |
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Kimmel DW, Rogers LM, Aronoff DM, Cliffel DE. Prostaglandin E2 regulation of macrophage innate immunity. Chemical Research in Toxicology 2016;29(1):19-25. |
R835738 (2017) R835736 (2016) |
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Knudsen TB, Keller DA, Sander M, Carney EW, Doerrer NG, Eaton DL, Fitzpatrick SC, Hastings KL, Mendrick DL, Tice RR, Watkins PB, Whelan M. FutureTox II: in vitro data and in silico models for predictive toxicology. Toxicological Sciences 2015;143(2):256-267. |
R835738 (2016) R835738C005 (2017) |
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Lee JH, Han JH, Kim JH, Kim B, Bello D, Kim JK, Lee GH, Sohn EK, Lee K, Ahn K, Faustman EM, Yu IJ. Exposure monitoring of graphene nanoplatelets manufacturing workplaces. Inhalation Toxicology 2016;28(6):281-291. |
R835738 (2016) |
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Lee JH, Sung JH, Ryu HR, Song KS, Song NW, Park HM, Shin BS, Ahn K, Gulumian M, Faustman EM, Yu IJ. Tissue distribution of gold and silver after subacute intravenous injection of co-administered gold and silver nanoparticles of similar sizes. Archives of Toxicology 2018;92(4):1393-1405. |
R835738 (2017) R835738C004 (2018) |
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Melnikov F, Botta D, White CC, Schmuck SC, Schaupp CM, Gallagher EP, Brooks BW, Williams ES, Coish P, Anastas PT, Voutchkova-Kostal A, Kostal J and Kavanagh TJ. Kinetics of Glutathione Depletion and Antioxidant Gene Expression as Indicators of Chemical Modes of Action Assessed in vitro in Mouse Hepatocytes with Enhanced Glutathione Synthesis. Chemical Research in Toxicology2019:32(3);421-436 |
R835738C001 (2018) R835738C003 (2018) R835738C004 (2018) |
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Monteiro, M. B., Ramm S, Chandrasekaran V, Boswell SA, Weber EJ, Lidberg KA, Kelly EJ, Vaidya VS. A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation. Journal of the American Society of Nephrology 2018:29(12);2820-2833. |
R835738C001 (2018) R835738C002 (2018) |
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Nicholas TP, Kavanaugh T, Faustman EM, Altermeier WA. The Effects of Gene × Environment Interactions on Silver Nanoparticle Toxicity in the Respiratory System. Chemical Research in Toxicology 2019:32(6); 952-968. |
R835738C001 (2018) R835642 (Final) |
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Nicholas T, Haik A, Bammler T, Workman T, Kavanaugh T, Faustman E, Gharib S, Altemeier W. The effects of genotype x phenotype interactions on transcriptional response to silver nanoparticle Toxicity in organotypic cultures of marine tracheal epithelial cells. Toxicological Sciences 2020;173(1):131-143. |
R835738 (2018) |
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Nocholas T, Haick A, Workman T, Griffith W, Nolin J, Kanahagh T, Faustman E, ALtemeir W. The effects of genotype x phenotype interactions on silver nanoparticle toxicity in organotypic cultures of murine tracheal epithelial cells. Nanotoxicology 2020;14(7):908-928 |
R835738 (2019) |
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Nolin JD, Lai Y, Ogden HL, Manicone AM, Murphy RC, An D, Frevert CW, Ghomashchi F, Naika GS, Gelb MH, Gauvreau GM, Piliponsky AM, Altemeier WA, Hallstrand TS. Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen. JCI Insight 2017;2(21):e94929 (18 pp.). |
R835738 (2017) R835738C001 (2018) R835738C002 (2017) |
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Nolin JD, Lai Y, Ogden HL, Manicone AM, Murphy RC, An D, Frevert CW, Ghomashchi F, Naika GS, Gelb MH, Gauvreau GM, Piliponsky AM, Altemeier WA, Hallstrand TS. Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen. JCI Insight 2017;2(21):94929 (18 pp.). |
R835738C001 (2017) |
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Park JJ, Weldon BA, Hong S, Workman T, Griffith WC, Park JH, Faustman EM. Characterization of 3D embryonic C57BL/6 and A/J mouse midbrain micromass in vitro culture systems for developmental neurotoxicity testing. Toxicology In Vitro 2018;48:33-44. |
R835738 (2017) R835738C001 (2018) R835738C004 (2018) R835738C005 (2018) |
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Ramaiahgari SC, Waidyanatha S, Dixon D, DeVito MJ, Paules RS, Ferguson SS. From the cover: three-dimensional (3D) hepaRG spheroid model with physiologically relevant xenobiotic metabolism competence and hepatocyte functionality for liver toxicity screening. Toxicological Sciences 2017;159(1):124-136. |
R835738 (2017) |
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Rountree A, Karkamkar A, Khalil G, Folch A, Cook DL, Sweet IR. BaroFuse, a novel pressure-driven, adjustable-throughput perfusion system for tissue maintenance and assessment. Heliyon 2016;2(12):e00210 (18 pp.). |
R835738 (2017) |
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Sakolish, C., Weber EJ, Kelly EJ, Himmelfarb J, Mouneimne R, Grimm FA, House JS, Wade T, Han A, Chiu WA, Rusyn I. Technology Transfer of the Microphysiological Systems: A Case Study of the Human Proximal Tubule Tissue Chip. Scientific Reports 2018: 8(1);14882 |
R835738C001 (2018) R835738C002 (2018) |
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Scoville DK, Botta D, Galdanes K, Schmuck SC, White CC, Stapleton PL, Bammler TK, MacDonald JW, Altemeier WA, Hernandez M, Kleeberger SR, Chen LC, Gordon T, Kavanagh TJ. Genetic determinants of susceptibility to silver nanoparticle-induced acute lung inflammation in mice. FASEB Journal 2017;31(10):4600-4611. |
R835738 (2017) R835738C001 (2017) R835738C001 (2018) R835738C002 (2017) |
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Scoville DK, White CC, Botta D, An D, Afsharinejad Z, Bammler TK, Gao X, Altemeier WA, Kavanagh TJ. Quantum dot induced acute changes in lung mechanics are mouse strain dependent. Inhalation Toxicology 2018; 30(9-10):397-403. |
R835738C001 (2018) |
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Scoville DK, Nolin JD, Ogden HL, An D, Afsharinejad Z, Johnson BW, Bammler TK, Gao X, Frevert CW, Altemeier WA, Hallstrand TS, Kavanagh TJ. Quantum dots and mouse strain influence house dust mite-induced allergic airway disease. TOXICOLOGY AND APPLIED PHARMACOLOGY 2019:368;55-62 |
R835738C001 (2018) |
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Shaffer R, Smith MN, Faustman EM. Developing the regulatory utility of the exposome: mapping exposures for risk assessment through Lifestage Exposome Snapshots (LEnS). Environmental Health Perspectives 2017;123(8):085003 (8 pp.). |
R835738 (2017) R835738C004 (2018) R835738C005 (2017) |
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Smith MN, Grice J, Cullen A, Faustman EM. A toxicological framework for the prioritization of Children’s Safe Product Act data. International Journal of Environmental Research and Public Health 2016;13(4):431 (24 pp.). |
R835738 (2016) R835738 (2017) R835738C005 (2015) R835738C005 (2016) R835738C005 (2017) R834514 (Final) |
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Smith M, Hubal E, Faustman E. A Case study on the utility of predictive toxicology tools in alternatives assessments for hazardous chemicals in children's consumer products. JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY 2020;30(1):160-170. |
R835738 (2018) |
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Van Ness KP, Chang SY, Weber EJ, Zumpano D, Eaton DL, Kelly EJ. Microphysiological systems to assess nonclinical toxicity. Current Protocols in Toxicology 2017;73(1):14.18.1-14.18.28. |
R835738 (2017) R835738C001 (2018) R835738C002 (2017) R835738C002 (2018) R835738C004 (2018) R835738C005 (2017) |
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Vernetti L, Gough A, Baetz N, Blutt S, Broughman JR, Brown JA, Foulke-Abel J, Hasan N, In J, Kelly E, Kovbasnjuk O, Repper J, Senutovitch N, Stabb J, Yeung C, Zachos NC, Donowitz M, Estes M, Himmelfarb J, Truskey G, Wikswo JP, Taylor DL. Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Scientific Reports 2017;7:42296 (14 pp.). |
R835738C002 (2017) R835738C005 (2017) R835736 (2017) R835736C004 (2018) |
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Vernetti L, Gough A, Baetz N, Blutt S, Broughman JR, Brown JA, Foulke-Abel J, Hasan N, In J, Kelly E, Kovbasnjuk O, Repper J, Senutovitch N, Stabb J, Yeung C, Zachos NC, Donowitz M, Estes M, Himmelfarb J, Truskey G, Wikswo JP, Taylor DL. Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Scientific Reports 2017;7:42296 (15 pp.). |
R835738 (2016) R835738C003 (2017) R835738C005 (2017) R835736 (2015) R835736 (2016) R835736C004 (2016) R835736C005 (2016) |
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Vernetti L, Gough A, Baetz N, Blutt S, Broughman JR, Brown JA, Foulke-Abel J, Hasan N, In J, Kelly E, Kovbasnjuk O, Repper J, Senutovitch N, Stabb J, Yeung C, Zachos NC, Donowitz M, Estes M, Himmelfarb J, Truskey G, Wikswo JP, Taylor DL. Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Scientific Reports 2017;7:42296 (14 pp.). |
R835738 (2017) R835738C002 (2016) R835736C004 (2017) |
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Vernetti L, Gough A, Baetz N, Blutt S, Broughman JR, Brown JA, Foulke-Abel J, Hasan N, In J, Kelly E, Kovbasnjuk O, Repper J, Senutovitch N, Stabb J, Yeung C, Zachos NC, Donowitz M Estes M, Himmelfarb J, Truskey G, Wikswo JP, Taylor DL. Corrigendum: Functional coupling of human microphysiology systems: intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle. Scientific Reports 2017;7:44517. |
R835738 (2016) R835738 (2017) R835738C002 (2016) R835738C002 (2017) R835738C005 (2017) |
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Wallace JC, Port JA, Smith MN, Faustman EM. FARME DB:a functional antibiotic resistance element database. Database 2017;2017(1):1-7. |
R835738 (2016) |
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Weber EJ, Chapron A, Chapron BD, Voellinger JL, Lidberg KA, Yeung CK, Wang Z, Yamaura Y, Hailey DW, Neumann T, Shen DD, Thummel KE, Muczynski KA, Himmelfarb J, Kelly EJ. Development of a microphysiological model of human kidney proximal tubule function. Kidney International 2016;90(3):627-637. |
R835738 (2016) R835738 (2017) R835738C002 (2016) R835738C002 (2017) |
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Weber EJ, Himmelfarb J, Kelly EJ. Concise review: current and emerging biomarkers of nephrotoxicity. Current Opinion in Toxicology 2017;4:16-21. |
R835738 (2017) R835738C002 (2017) R835738C002 (2018) |
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Wegner SH, Yu X, Pacheco Shubin S, Griffith WC, Faustman EM. Stage-specific signaling pathways during murine testis development and spermatogenesis: a pathway-based analysis to quantify developmental dynamics. Reproductive Toxicology 2015;51:31-39. |
R835738 (2016) R835738 (2017) R835738C004 (2015) R835738C004 (2017) R834514 (2015) R834514 (Final) R834514C003 (2015) R834514C003 (Final) |
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Wegner S, Park J, Workman T, Workman T, Hermsan S, Wallace J, Stanaway I, Kim H, Griffith W, Hong S, Faustman E. Anchoring a dynamic in vitro model of human neuronal differentiation to key processes of early brain development in vivo. Reproductive Toxicology 2020;91:116-130. |
R835738 (2018) R834514 (Final) |
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Wegner S, Workman T, Park J, Harris S, Wallace J, Stanaway I, Hong S, Hansen B, Griffith W, Faustman E. A dynamic in vitro developing testis model reflects structures and functions of testicular development in vivo. REPRODUCTIVE TOXICOLOGY 2023;118(108362) |
R835738 (Final) R834514 (Final) |
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Weldon BA, Faustman EM, Oberdorster G, Workman T, Griffith WC, Kneuer C, Yu IJ. Occupational exposure limit for silver nanoparticles: considerations on the derivation of a general health-based value. Nanotoxicology 2016;10(7):945-956. |
R835738 (2015) R835738 (2016) R835738 (2017) R835738C005 (2015) R835738C005 (2016) R835738C005 (2017) |
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Weldon BA, Park JJ, Hong S, Workman T, Dills R, Lee JH, Griffith WC, Kavanagh TJ, Faustman EM. Using primary organotypic mouse midbrain cultures to examine developmental neurotoxicity of silver nanoparticles across two genetic strains. Toxicology and Applied Pharmacology 2018:354;215-224 |
R835738 (2017) R835738C004 (2017) R835738C004 (2018) R835738C005 (2017) R835738C005 (2018) |
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ZImaoka T, Yang J, Wang L, McDonald M, Afsharinejad Z, Bammler T, Van Ness K, Yeung C, Rettie A, Himmelfarb J. Microphysiological system modeling of ochratoxin A-associated nephrotoxicity. Toxicology 2020;444. |
R835738 (2019) |
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Lee JH, Sung JH, Ryu HR, Song KS, Song NW, Park HM, Shin BS, Ahn K, Gulumian M, Faustman EM, Yu IJ. Tissue Distribution of Gold and Silver after Subacute Intravenous Injection of Co-administered Gold and Silver Nanoparticles of similar sizes. Archives of Toxicology 2018:92(4);1393-1405 |
R835738C004 (2018) R835738C005 (2018) |
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Weldon BA, Griffith WC, Workman T, Scoville DK, Kavanagh TJ, Faustman EM. 2018. In vitro to in vivo benchmark dose comparisons to inform risk assessment of quantum dot nanomaterials. Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology 2018;10(4):e1507. |
R835738 (2017) R835738C001 (2018) R835738C004 (2017) R835738C004 (2018) R835738C005 (2017) R835738C005 (2018) |
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Van Ness, K, & Kelly, E. Excretory Processes in Toxicology:Drug Transporters in Drug Development. In:McQueen, C. A., Comprehensive Toxicology, (2018) Third Edition. Vol. 1, pp. 143–164. Oxford:Elsevier Ltd. |
R835738C002 (2018) |
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Weber EJ, Lidberg KA, Wang L, Bammler TK, MacDonald JW, Li MJ, Redhair M, Atkins WM, Tran C, Hines KM, Herron J, Xu L, Monteiro MB, Ramm S, Vaidya V, Vaara M, Vaara T, Himmelfarb J, Kelly EJ. “Human Kidney on a Chip Assessment of Polymyxin Antibiotic Nephrotoxicity” JCI Insight:3(24) e123673. |
R835738C002 (2018) |
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Supplemental Keywords:
organotypic models, decision-making, engineered nanomaterials, adverse outcome pathwayRelevant Websites:
The Effects of Genotype × Phenotype Interactions on Silver Nanoparticle Toxicity in Organotypic Cultures of Murine Tracheal Epithelial Cells Exit
Progress and Final Reports:
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R835738C001 Airway Epithelium Organotypic Culture as a Platform forAdverseOutcomesPathway Assessment of Engineered Nanomaterials
R835738C002 Organotypic Model of Human Kidney as a Platform for Adverse Outcomes
Pathway Assessment of Engineered Nanomaterials
R835738C003 Organotypic Models of Mammalian Liver as a Platform for Adverse Outcomes
Pathway Assessment of Engineered Nanomaterials
R835738C004 Organotypic Model of Testis as a Platform for Adverse Outcomes Pathway
Assessment of Engineered Nanomaterials
R835738C005 Integrating Liver, Kidney and Testis Nanomaterial Toxicity using the
Adverse Outcome Pathway Approach
The 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
- 2019 Progress Report
- 2018 Progress Report
- 2017 Progress Report
- 2016 Progress Report
- 2015 Progress Report
49 journal articles for this center