Comprehensive In Vitro Toxicity Testing of a Panel of Representative Oxide Nanomaterials: First Steps towards an Intelligent Testing Strategy
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{"title"=>"Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials: First steps towards an intelligent testing strategy", "type"=>"journal", "authors"=>[{"first_name"=>"Lucian", "last_name"=>"Farcal", "scopus_author_id"=>"55816335000"}, {"first_name"=>"Fernando Torres", "last_name"=>"Andón", "scopus_author_id"=>"55366045300"}, {"first_name"=>"Luisana", "last_name"=>"Di Cristo", "scopus_author_id"=>"36650527200"}, {"first_name"=>"Bianca Maria", "last_name"=>"Rotoli", "scopus_author_id"=>"7102998133"}, {"first_name"=>"Ovidio", "last_name"=>"Bussolati", "scopus_author_id"=>"7004670564"}, {"first_name"=>"Enrico", "last_name"=>"Bergamaschi", "scopus_author_id"=>"7004555643"}, {"first_name"=>"Agnieszka", "last_name"=>"Mech", "scopus_author_id"=>"55863247300"}, {"first_name"=>"Nanna B.", "last_name"=>"Hartmann", "scopus_author_id"=>"23110420600"}, {"first_name"=>"Kirsten", "last_name"=>"Rasmussen", "scopus_author_id"=>"7402496547"}, {"first_name"=>"Juan", "last_name"=>"Riego-Sintes", "scopus_author_id"=>"6507896588"}, {"first_name"=>"Jessica", "last_name"=>"Ponti", "scopus_author_id"=>"6506875213"}, {"first_name"=>"Agnieszka", "last_name"=>"Kinsner-Ovaskainen", "scopus_author_id"=>"25644543300"}, {"first_name"=>"François", "last_name"=>"Rossi", "scopus_author_id"=>"7401756340"}, {"first_name"=>"Agnes", "last_name"=>"Oomen", "scopus_author_id"=>"7003479948"}, {"first_name"=>"Peter", "last_name"=>"Bos", "scopus_author_id"=>"7101764869"}, {"first_name"=>"Rui", "last_name"=>"Chen", "scopus_author_id"=>"56673181300"}, {"first_name"=>"Ru", "last_name"=>"Bai", "scopus_author_id"=>"56522432600"}, {"first_name"=>"Chunying", "last_name"=>"Chen", "scopus_author_id"=>"56506076900"}, {"first_name"=>"Louise", "last_name"=>"Rocks", "scopus_author_id"=>"47161489500"}, {"first_name"=>"Norma", "last_name"=>"Fulton", "scopus_author_id"=>"56673922800"}, {"first_name"=>"Bryony", "last_name"=>"Ross", "scopus_author_id"=>"24598062100"}, {"first_name"=>"Gary", "last_name"=>"Hutchison", "scopus_author_id"=>"8953866500"}, {"first_name"=>"Lang", "last_name"=>"Tran", "scopus_author_id"=>"7102277627"}, {"first_name"=>"Sarah", "last_name"=>"Mues", "scopus_author_id"=>"56674736200"}, {"first_name"=>"Rainer", "last_name"=>"Ossig", "scopus_author_id"=>"6603205920"}, {"first_name"=>"Jürgen", "last_name"=>"Schnekenburger", "scopus_author_id"=>"7004687491"}, {"first_name"=>"Luisa", "last_name"=>"Campagnolo", "scopus_author_id"=>"6507627927"}, {"first_name"=>"Lucia", "last_name"=>"Vecchione", "scopus_author_id"=>"16030022600"}, {"first_name"=>"Antonio", "last_name"=>"Pietroiusti", "scopus_author_id"=>"6701617659"}, {"first_name"=>"Bengt", "last_name"=>"Fadeel", "scopus_author_id"=>"56229143000"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0127174", "pui"=>"604612365", "pmid"=>"25996496", "sgr"=>"84930653106", "isbn"=>"1083-351X (Electronic)\\r0021-9258 (Linking)", "scopus"=>"2-s2.0-84930653106", "issn"=>"19326203"}, "id"=>"a1126579-5779-31db-8f03-76865042129d", "abstract"=>"Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry - hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO - uncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO2 NMs produced by two different manufacturing techniques - precipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST) classified the TiO2 NMs as potentially 'weak-embryotoxic' and ZnO and SiO2 NMs as 'non-embryotoxic'. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103). This ranking was different in the case of embryonic tissues, for which TiO2 displayed higher toxicity compared with ZnO and SiO2. Importantly, the in vitro methodology applied could identify cell- and NM-specific responses, with a low variability observed between different test assays. Overall, this testing approach, based on a battery of cellular systems and test assays, complemented by an exhaustive physico-chemical characterization of NMs, could be deployed for the development of an ITS suitable for risk assessment of NMs. This study also provides a rich source of data for modeling of NM effects.", "link"=>"http://www.mendeley.com/research/comprehensive-vitro-toxicity-testing-panel-representative-oxide-nanomaterials-first-steps-towards-in", "reader_count"=>40, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>12, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Other"=>5, "Student > Master"=>7, "Student > Bachelor"=>2, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>12, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Other"=>5, "Student > Master"=>7, "Student > Bachelor"=>2, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Environmental Science"=>8, "Biochemistry, Genetics and Molecular Biology"=>3, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>6, "Pharmacology, Toxicology and Pharmaceutical Science"=>5, "Chemistry"=>1, "Computer Science"=>2, "Materials Science"=>2, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Chemistry"=>{"Chemistry"=>1}, "Materials Science"=>{"Materials Science"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Computer Science"=>{"Computer Science"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Environmental Science"=>{"Environmental Science"=>8}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Sweden"=>1, "Norway"=>1, "Bulgaria"=>1, "Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2077879"], "description"=>"<p>The IC<sub><b>50</b></sub> values of the six representative NMs in different cellular systems calculated at different time points (24 to 72h or 10 days). The heat map shows a higher toxicity of ZnO NMs, followed by SiO<sub><b>2</b></sub> and TiO<sub><b>2</b></sub>. The highest sensitivity after short term exposure to NMs was noted in the case of murine alveolar macrophages (MH-S) while Calu-3 were the most resistant cells. The long term exposure (10 days) of NIH3T3 and mES cells to NMs induced also significant cytotoxic effect.</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422400, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g003", "stats"=>{"downloads"=>3, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heat_map_representation_of_IC_50_values_/1422400", "title"=>"Heat map representation of IC<sub>50</sub> values.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077892"], "description"=>"<p>The following parameters were used for EST: viability of NIH-3T3 (A, B, C) and mES cells (D, E, F), respectively the mES differentiation into contracting EBs (G, H, I). The cell viability was evaluated by WST-1 assay on day 10 after exposure and the cell differentiation was assessed by direct visualization of beating areas under a light microscope after exposure to different concentrations of TiO<sub><b>2</b></sub> (NM-103 and NM-104), ZnO (NM-110 and NM-111) or SiO<sub><b>2</b></sub> (NM-200 and NM-203). The values represent the means ± SE of at least four independent experiments.</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422413, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g010", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Embryotoxicity_evaluation_by_Embryonic_Stem_Cell_Test_EST_/1422413", "title"=>"Embryotoxicity evaluation by Embryonic Stem Cell Test (EST).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077877"], "description"=>"<p>Target organs or systems for NMs in the present study: immune system (HMDM, RAW264.7 and MH-S), respiratory system (Calu-3, 16HBE and RLE-6TN), male reproductive system (TM3 and TM4), gastrointestinal system (Caco-2), kidneys (NRK-52E) and embryo (NIH-3T3 and mES/D3).</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422398, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g002", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cellular_models_selected_for_the_in_vitro_toxicity_study_/1422398", "title"=>"Cellular models selected for the <i>in vitro</i> toxicity study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077891"], "description"=>"<p>The cell viability by WST-1 assay was evaluated in TM3 cells (A, B and C) and TM4 cells (D, E and F) following the exposure for 24h to TiO<sub><b>2</b></sub> NM-103 and NM-104, ZnO NM-110 and NM-111 and SiO2 NM-200 and NM-203. The ranges of doses used were between 0.125 μg/ml (0.037 μg/cm<sup>2</sup>) and 200 μg/ml (60.24 μg/cm<sup>2</sup>). WST-1 assay measurements were taken (120 min post addition). All results were corrected for WST-1, as the control showed presence of interference in absorbance reading as a result of WST. The statistical analysis of the data (n = 6) was performed by one way ANOVA, Dunnett's multiple comparison test and Tukey’s post-hoc test (p<0.001*).</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422412, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g009", "stats"=>{"downloads"=>4, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_on_male_reproductive_cells_TM3_Leydig_and_TM4_Sertoli_/1422412", "title"=>"Effects on male reproductive cells (TM3 Leydig and TM4 Sertoli).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077886"], "description"=>"<p>Comparative evaluation of cell viability evaluated by resazurin assay (A and B) and NRU assay (C and D) after exposure to ZnO (NM-110 and NM-111). Cells were grown for 24h in complete growth medium and then exposed for 24h, 48h and 72h to different concentrations of ZnO NMs. At the end of the incubation, cell viability was assessed using two different assays (resazurin and NRU). Data are means ± SD of 10 independent determinations in two separate experiments. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post-hoc test. *p< 0.05, **p< 0.01, ***p< 0.001.</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422407, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g006", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_on_immune_cells_MH_S_murine_alveolar_macrophages_/1422407", "title"=>"Effects on immune cells (MH-S murine alveolar macrophages).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077887"], "description"=>"<p>Cell viability was evaluated by resazurin (A and B) and NRU (C and D) assays after exposure to ZnO NM-110 and NM-111. Calu-3 cells were grown for 24h in complete growth medium and then exposed for 24h, 48h and 72h to different concentrations of ZnO NMs. At the end of the incubation, cell viability was assessed using two different assays (resazurin and NRU). Data are means ± SD of 10 independent determinations in two separate experiments. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post-hoc test. *p< 0.05, **p< 0.01, ***p< 0.001.</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422408, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g007", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_on_airway_epithelial_cells_Calu_3_bronchial_cells_/1422408", "title"=>"Effects on airway epithelial cells (Calu-3 bronchial cells).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077882"], "description"=>"<p>Cell viability was evaluated using LDH assay after 24h of exposure to TiO<sub><b>2</b></sub> NM-103 and NM-104 (A), ZnO NM-110 and NM-111 (B) or SiO<sub><b>2</b></sub> NM-200 and NM-203 (C). The results are expressed as % of cell viability (mean ± SD) versus control cells (100%) and are obtained from three to four independent experiments (donors). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post-hoc test (*p< 0.05, **p < 0.01, ***p < 0.001).</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422403, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g004", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_on_immune_cells_primary_human_monocyte_derived_macrophages_/1422403", "title"=>"Effects on immune cells (primary human monocyte-derived macrophages).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077894"], "description"=>"<p>The cytotoxic and cytostatic effects were evaluated by Colony Forming Efficiency Assay (CFE) in Caco-2 cells exposed to 100 μg/ml of TiO<sub><b>2</b></sub> (NM-103 and NM-104) (A) and SiO<sub><b>2</b></sub> (NM-200 and NM-203) (B) for 3 (short exposure) and 10 days (long term, repeated-dose exposure). The results are expressed as CFE (% of solvent control) = ([average No. of treatment colonies/average No. of solvent control colonies] × 100). The solvent control (0.05% BSA) did not induce cytotoxicity. Data are reported as means ± SEM (standard error mean = standard deviation/√number of replicates). One-way analysis of variance (ANOVA) with post hoc test (Dunnett's Multiple Comparison Test) for comparing groups of data versus one control group was used (** p<0.01; *** p<0.001).</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422415, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g011", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_on_the_gastrointestinal_tract_Caco_2_intestinal_cells_/1422415", "title"=>"Effects on the gastrointestinal tract (Caco-2 intestinal cells).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077875"], "description"=>"<p>Ten different assays were used for the evaluation of cytotoxicity (resazurin, NRU, WST-1, WST-8, LDH and CFE), embryotoxicity (EST), epithelial integrity (TEER), cytokine secretion (ELISA) and oxidative stress (DCF) on twelve different cellular systems.</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422396, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Methodology_applied_for_the_in_vitro_toxicity_assessment_/1422396", "title"=>"Methodology applied for the in vitro toxicity assessment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077889"], "description"=>"<p>Evaluation of TEER during the exposure to TiO2 NM-103 (A) and NM-104 (B), ZnO NM-110 (C) and NM-111 (D) and SiO2 NM-200 (E) and NM-203 (F). Calu-3 epithelial cells were grown for 10 days in a double-chamber culture system to form a tight monolayer. The epithelial monolayer was then exposed at the apical side to different concentrations of NMs: 128 μg/ml (80 μg/cm²) of TiO2 and SiO2, 32 μg/ml (20 μg/cm²) and 64 μg/ml (40 μg/cm²) of ZnO. The trans-epithelial electrical resistance (TEER) was measured at the indicated times with a voltohmeter. Data are values obtained from 12 monolayers used in three separate experiments and are expressed as % of the initial value ± SD (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127174#sec019\" target=\"_blank\">Methods</a>). Statistical analysis was performed using two-way ANOVA followed by Bonferroni post-hoc test. **p< 0.01, ***p< 0.001.</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422410, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g008", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_on_the_airway_epithelial_cell_barrier_formed_by_Calu_3_cells_/1422410", "title"=>"Effects on the airway epithelial cell barrier formed by Calu-3 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077884"], "description"=>"<p>Comparative evaluation of cell viability by resazurin assay (A and B) and NRU assay (C and D) after exposure to ZnO (NM-110 and NM-111). Cells were grown for 24h in complete growth medium and then exposed for 24h, 48h and 72h to different concentrations of ZnO NMs. At the end of the incubation, cell viability was assessed using two different assays (resazurin and NRU). Data are means ± SD of 10 independent determinations in two separate experiments. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post-hoc test. *p< 0.05, **p< 0.01, ***p< 0.001.</p>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422405, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0127174.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_on_immune_cells_RAW_264_7_murine_macrophages_/1422405", "title"=>"Effects on immune cells (RAW 264.7 murine macrophages).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-21 03:01:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2077898", "https://ndownloader.figshare.com/files/2077899", "https://ndownloader.figshare.com/files/2077900"], "description"=>"<div><p>Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate <i>in vitro</i> test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The <i>in vitro</i> toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO<sub>2</sub> NMs with different surface chemistry – hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO – uncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO<sub>2</sub> NMs produced by two different manufacturing techniques – precipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO<sub>2</sub>>TiO<sub>2</sub>). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO<sub>2</sub> and SiO<sub>2</sub>, while the embryonic stem cell test (EST) classified the TiO<sub>2</sub> NMs as potentially ‘weak-embryotoxic’ and ZnO and SiO<sub>2</sub> NMs as ‘non-embryotoxic’. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO<sub>2</sub> NM-203 > SiO<sub>2</sub> NM-200 > TiO<sub>2</sub> NM-104 > TiO<sub>2</sub> NM-103). This ranking was different in the case of embryonic tissues, for which TiO<sub>2</sub> displayed higher toxicity compared with ZnO and SiO<sub>2</sub>. Importantly, the <i>in vitro</i> methodology applied could identify cell- and NM-specific responses, with a low variability observed between different test assays. Overall, this testing approach, based on a battery of cellular systems and test assays, complemented by an exhaustive physico-chemical characterization of NMs, could be deployed for the development of an ITS suitable for risk assessment of NMs. This study also provides a rich source of data for modeling of NM effects.</p></div>", "links"=>[], "tags"=>["SiO 2. Importantly", "Intelligent Testing Strategy Nanomaterials", "risk assessment", "representative oxide NMs", "Representative Oxide Nanomaterials", "TiO 2 NMs", "fp", "test assays", "Vitro Toxicity Testing", "toxicity assessment", "cell barrier integrity", "SiO 2 NMs", "TiO 2", "est"], "article_id"=>1422419, "categories"=>["Biological Sciences"], "users"=>["Lucian Farcal", "Fernando Torres Andón", "Luisana Di Cristo", "Bianca Maria Rotoli", "Ovidio Bussolati", "Enrico Bergamaschi", "Agnieszka Mech", "Nanna B. Hartmann", "Kirsten Rasmussen", "Juan Riego-Sintes", "Jessica Ponti", "Agnieszka Kinsner-Ovaskainen", "François Rossi", "Agnes Oomen", "Peter Bos", "Rui Chen", "Ru Bai", "Chunying Chen", "Louise Rocks", "Norma Fulton", "Bryony Ross", "Gary Hutchison", "Lang Tran", "Sarah Mues", "Rainer Ossig", "Jürgen Schnekenburger", "Luisa Campagnolo", "Lucia Vecchione", "Antonio Pietroiusti", "Bengt Fadeel"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0127174.s001", "https://dx.doi.org/10.1371/journal.pone.0127174.s002", "https://dx.doi.org/10.1371/journal.pone.0127174.s003"], "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Comprehensive_In_Vitro_Toxicity_Testing_of_a_Panel_of_Representative_Oxide_Nanomaterials_First_Steps_towards_an_Intelligent_Testing_Strategy/1422419", "title"=>"Comprehensive <i>In Vitro</i> Toxicity Testing of a Panel of Representative Oxide Nanomaterials: First Steps towards an Intelligent Testing Strategy", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-05-21 03:01:49"}

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  • {"unique-ip"=>"42", "full-text"=>"50", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"44", "full-text"=>"46", "pdf"=>"20", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"49", "full-text"=>"44", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"25", "full-text"=>"27", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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