Funding period: 2019-2024
Lead: Sabina Halappanavar
Total GRDI funding: $870,000
Engineered nanomaterials are a novel class of materials that are 1-100 nanometres in size. Health Canada is responsible for regulating products that contain such materials. When inhaled, engineered nanomaterials can induce harmful effects in experimental animals; however, quality toxicological data are currently not available for an effective assessment of risk to human health. This project generates experimental data to support the risk assessment of a select set of nanaomaterials. The acquired knowledgebase and methods can be used by Health Canada to screen for potential toxicities of novel nanomaterials of concern in Canada.
Publications
- Boyadzhiev A, Avramescu M-L, Wu D, Williams A, Rasmussen P. 2021. Impact of copper oxide particle solubility on lung epithelial cell toxicity: response characterization using global transcriptional analysis. Nanotoxicology. Nanotoxicology. 15(3):380-399. https://doi.org/10.1080/17435390.2021.1872114
- Boyadzhiev A, Solorio-Rodriguez SA, Wu D, Avramescu ML, Rasmussen P, Halappanavar S. The High-Throughput In Vitro CometChip Assay for the Analysis of Metal Oxide Nanomaterial Induced DNA Damage. Nanomaterials (Basel). 2022 May 27;12(11):1844. https://doi.org/10.3390/nano12111844
- Boyadzhiev A, Wu D, Avramescu ML, Williams A, Rasmussen P, Halappanavar S. Toxicity of Metal Oxide Nanoparticles: Looking through the Lens of Toxicogenomics. Int J Mol Sci. 2023 Dec 30;25(1):529. https://doi.org/10.3390/ijms25010529
- Gosens I, Costa PM, Olsson M, Stone V, Costa AL, Brunelli A, Badetti E, Bonetto A, Bokkers BGH, de Jong WH, Williams A, Halappanavar S, Fadeel B, Cassee FR. Pulmonary toxicity and gene expression changes after short-term inhalation exposure to surface-modified copper oxide nanoparticles. NanoImpact. 2021 Apr;22:100313. https://doi.org/10.1016/j.impact.2021.100313
- Clerbaux LA, Amigó N, Amorim MJ, Bal-Price A, Batista Leite S, Beronius A, Bezemer GFG, Bostroem AC, Carusi A, Coecke S, Concha R, Daskalopoulos EP, De Bernardi F, Edrosa E, Edwards SW, Filipovska J, Garcia-Reyero N, Gavins FNE, Halappanavar S, et al. 2022. COVID-19 through Adverse Outcome Pathways: Building networks to better understand the disease - 3rd CIAO AOP Design Workshop. ALTEX. 39(2):322–335. https://doi.org/10.14573/altex.2112161
- Doak SH, Clift MJD, Costa A, Delmaar C, Gosens I, Halappanavar S, Kelly S, Pejinenburg WJGM, Rothen-Rutishauser B, Schins RPF, Stone V, Tran L, Vijver MG, Vogel U, Wohlleben W, Cassee FR. 2022. The Road to Achieving the European Commission's Chemicals Strategy for Nanomaterial Sustainability-A PATROLS Perspective on New Approach Methodologies. Small. 2022 Apr;18(17):e2200231. https://doi.org/10.1002/smll.202200231
- Gromelski M, Stoliński F, Jagiello K, Rybińska-Fryca A, Williams A, Halappanavar S, Vogel U, Puzyn T. AOP173 key event associated pathway predictor – online application for the prediction of benchmark dose lower bound (BMDLs) of a transcriptomic pathway involved in MWCNTs-induced lung fibrosis. Nanotoxicology. 2022 Mar;16(2):183-194. https://doi.org/10.1080/17435390.2022.2064250
- Halappanavar S, et al. 2023. Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis, OECD Series on Adverse Outcome Pathways, No. 33, OECD Publishing, Paris, https://doi.org/10.1787/10372cb8-en
- Halappanavar S, Ede JD, Krug HF, Mahapatra I, Krug HF, Kuempel ED, Lynch I, Vandebriel RJ, Shatkin JA. 2021. A methodology for developing key events to advance nanomaterial-relevant adverse outcome pathways to inform risk assessment. Nanotoxicology. 15(3):289-310. https://doi.org/10.1080/17435390.2020.1851419
- Halappanavar S, Ede JD, Shatkin JA, Krug HF. 2019. A systematic process for identifying key events for advancing the development of nanomaterial relevant adverse outcome pathways. NanoImpact. 15:e100178. https://doi.org/10.1016/j.impact.2019.100178
- Halappanavar S, Nymark P, Krug HF, Martin JD, Clift MJD, Rothen-Rutishauser B, Vogel U. 2021. Non-animal strategies for toxicity assessment of nanoscale materials: role of adverse outcome pathways in the selection of endpoints. Small. 17(15):e 2007628 https://doi.org/10.1002/smll.202007628
- Halappanavar S, Rahman L, Nikota J, Poulsen SS, Ding Y, Jackson P, Wallin H, Schmid O, Vogel U, Williams A. 2019. Ranking of nanomaterial potency to induce pathway perturbations associated with lung responses. NanoImpact. 14:e100158. https://doi.org/10.1016/j.impact.2019.100158
- Halappanavar S, van den Brule S, Nymark P, Gaté L, Seidel C, Valentino S, Zhernovkov V, Høgh Danielsen P, De Vizcaya A, Wolff H, Stöger T, Boyadziev A, Poulsen SS, Sørli JB, Birkelund J, Vogel U. 2020. Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale. Part. Fibre Toxicol. 17(1):16. https://doi.org/10.1186/s12989-020-00344-4
- Nymark P, Karlsson HL, Halappanavar S, Vogel U. 2021. Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles. Front Toxicol. 3:653386. https://doi.org/10.3389/ftox.2021.653386
- Poulsen SS, Bengston S, Williams A, Jacobsen NR, Troelsen JT, Halappanavar S, Vogel U. 2021. A transcriptomic overview of lung and liver changes one day after pulmonary exposure to graphene and graphene oxide. Toxicol. Appl. Pharmacol. 410:e115343. https://doi.org/10.1016/j.taap.2020.115343
- Jagiello K, Halappanavar S, Rybińska-Fryca A, Willliams A, Vogel U, Puzyn T. 2021. Transcriptomics-based and AOP-informed structure-activity relationships to predict pulmonary pathology induced by multiwalled carbon nanotubes. Small. 17(15):e2003465. https://doi.org/10.1002/smll.202003465
- Rahman L, Williams A, Gelda K, Nikota J, Wu D, Vogel U, Halappanavar S. 2020. 21st century tools for nanotoxicology: transcriptomic biomarker panel and precision-cut lung slice srgan mimic system for the assessment of nanomaterial-induced lung fibrosis. 16(36):e2000272. https://doi.org/10.1002/smll.202000272
- Saber AT, Hadrup N, Williams A, Mortensen A, Szarek J, Kyjovska Z, Kurz A, Jacobsen NR, Wallin H, Halappanavar S, Vogel U. 2022. Unchanged pulmonary toxicity of ZnO nanoparticles formulated in a liquid matrix for glass coating. Nanotoxicology. 2022 Aug-Oct;16(6-8):812-827. https://doi.org/10.1080/17435390.2022.2152751
- Serra A, Del Giudice G, Kinaret PAS, Saarimäki LA, Poulsen SS, Fortino V, Halappanavar S, Vogel U, Greco D. 2022. Characterization of ENM Dynamic Dose-Dependent MOA in Lung with Respect to Immune Cells Infiltration. Nanomaterials (Basel). 2022 Jun 13;12(12):2031. https://doi.org/10.3390/nano12122031
- Solorio-Rodriguez SA, Williams A, Poulsen SS, Knudsen KB, Jensen KA, Clausen PA, Danielsen PH, Wallin H, Vogel U, Halappanavar S. 2023. Single-Walled vs. Multi-Walled Carbon Nanotubes: Influence of Physico-Chemical Properties on Toxicogenomics Responses in Mouse Lungs. Nanomaterials (Basel). 2023 Mar 15;13(6):1059. https://doi.org/10.3390/nano13061059
- Solorio-Rodriguez SA, Wu D, Boyadzhiev A, Christ C, Williams A, Halappanavar S. 2024. A Systematic Genotoxicity Assessment of a Suite of Metal Oxide Nanoparticles Reveals Their DNA Damaging and Clastogenic Potential. Nanomaterials (Basel). Apr 24;14(9):743. https://doi.org/10.3390/nano14090743
Contact us
For additional information, please contact:
Genomics R&D Initiative
Email: info@grdi-irdg.collaboration.gc.ca