In: Ecotoxicology and environmental safety: EES ; official journal of the International Society of Ecotoxicology and Environmental safety, Band 92, S. 303-311
[Abstract] Standard toxicity tests might not be fully adequate for evaluating nanomaterials since their unique features are also responsible for unexpected interactions. The in vitro cytokinesis-block micronucleus (CBMN) test is recommended for genotoxicity testing, but cytochalasin-B (Cyt-B) may interfere with nanoparticles (NP), leading to inaccurate results. Our objective was to determine whether Cyt-B could interfere with MN induction by TiO2 NP in human SH-SY5Y cells, as assessed by CBMN test. Cells were treated for 6 or 24 h, according to three treatment options: co-treatment with Cyt-B, post-treatment, and delayed co-treatment. Influence of Cyt-B on TiO2 NP cellular uptake and MN induction as evaluated by flow cytometry (FCMN) were also assessed. TiO2 NP were significantly internalized by cells, both in the absence and presence of Cyt-B, indicating that this chemical does not interfere with NP uptake. Dose-dependent increases in MN rates were observed in CBMN test after co-treatment. However, FCMN assay only showed a positive response when Cyt-B was added simultaneously with TiO2 NP, suggesting that Cyt-B might alter CBMN assay results. No differences were observed in the comparisons between the treatment options assessed, suggesting they are not adequate alternatives to avoid Cyt-B interference in the specific conditions tested. ; This research was funded by Ministerio de Ciencia e Innovación (PID2020-114908GA-I00), Xunta de Galicia (ED431B 2019/02); NanoBioBarriers (PTDC/MED-TOX/31162/2017) funded by Operational Program for Competitiveness and Internationalisation through European Regional Development Funds (FEDER/FNR) and through national funds by the Portuguese Foundation for Science and Technology (FCT); NanoLegaTox (PTDC/SAU-PUB/29651/2017) project co-financed by COMPETE 2020, Portugal 2020 and European Union, through FEDER; Ministerio de Educación, Cultura y Deporte (BEAGAL18/00142, to V.V.); FCT (SFRH/BD/101060/2014, to F.B.); and CA17140 NANO2CLINIC COST Action ; Xunta de Galicia; ED431B 2019/02 ; Portugal. Fundação para a Ciência e a Tecnologia; PTDC/MED-TOX/31162/2017 ; Portugal. Fundação para a Ciência e a Tecnologia; PTDC/SAU-PUB/29651/2017 ; Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BD/101060/2014
(This article belongs to the Special Issue Toxicity of Nanomaterials and Legacy Contaminants: Risks to the Environment and Human Health) ; Standard toxicity tests might not be fully adequate for evaluating nanomaterials since their unique features are also responsible for unexpected interactions. The in vitro cytokinesis-block micronucleus (CBMN) test is recommended for genotoxicity testing, but cytochalasin-B (Cyt-B) may interfere with nanoparticles (NP), leading to inaccurate results. Our objective was to determine whether Cyt-B could interfere with MN induction by TiO2 NP in human SH-SY5Y cells, as assessed by CBMN test. Cells were treated for 6 or 24 h, according to three treatment options: co-treatment with Cyt-B, post-treatment, and delayed co-treatment. Influence of Cyt-B on TiO2 NP cellular uptake and MN induction as evaluated by flow cytometry (FCMN) were also assessed. TiO2 NP were significantly internalized by cells, both in the absence and presence of Cyt-B, indicating that this chemical does not interfere with NP uptake. Dose-dependent increases in MN rates were observed in CBMN test after co-treatment. However, FCMN assay only showed a positive response when Cyt-B was added simultaneously with TiO2 NP, suggesting that Cyt-B might alter CBMN assay results. No differences were observed in the comparisons between the treatment options assessed, suggesting they are not adequate alternatives to avoid Cyt-B interference in the specific conditions tested. ; This research was funded by Ministerio de Ciencia e Innovación (PID2020-114908GA-I00), Xunta de Galicia (ED431B 2019/02); NanoBioBarriers (PTDC/MED-TOX/31162/2017) funded by Operational Program for Competitiveness and Internationalisation through European Regional Development Funds (FEDER/FNR) and through national funds by the Portuguese Foundation for Science and Technology (FCT); NanoLegaTox (PTDC/SAU-PUB/29651/2017) project co-financed by COMPETE 2020, Portugal 2020 and European Union, through FEDER; Ministerio de Educación, Cultura y Deporte ...
[Abstrac] Titanium dioxide nanoparticles (TiO2 NPs) have a wide variety of applications in many consumer products, including as food additives, increasing the concern about the possible hazards that TiO2 NPs may pose to human health. Although most previous studies have focused on the respiratory system, ingestion must also be considered as an important exposure route. Furthermore, after inhalation or ingestion, TiO2 NPs can reach several organs, such as the liver, brain or lungs. Taking this into consideration, the present study focuses on the uptake and potential genotoxicity (micronuclei induction) of TiO2 NPs on four human cell lines of diverse origin: lung cells (A549), liver cells (HepG2), glial cells (A172) and neurons (SH-SY5Y), using flow cytometry methods. Results showed a concentration-, time- and cell-type- dependent increase in TiO2 NPs uptake but no significant induction of micronuclei in any of the tested conditions. Data obtained reinforce the importance of cell model and testing protocols choice for toxicity assessment. However, some questions remain to be answered, namely on the role of cell culture media components on the agglomeration state and mitigation of TiO2 NPs toxic effects. ; The present work was supported by Xunta de Galicia (reference ED431B 2019/02), NanoBioBarriers (PTDC/MED-TOX/31162/2017) funded by Operational Program for Competitiveness and Internationalisation through European Regional Development Funds (FEDER/FNR) and through national funds by the Portuguese Foundation for Science and Technology (FCT) and NanoLegaTox (PTDC/SAU-PUB/29651/2017) project co-financed by COMPETE 2020, Portugal 2020 and European Union, through FEDER. F.B. are M.J.B. recipients of FCT fellowships (SFRH/BD/101060/2014 and SFRH/BD/12046/2016); V.V. is supported by a Beatriz Galindo Research Fellowship (reference BEAGAL18/00142); and NF-B by a Deputación Provincial da Coruña fellowship (2019000011550) ; Xunta de Galicia; ED431B 2019/02 ; Portugal. Fundação para a Ciência e a Tecnologia; PTDC/MED-TOX/31162/2017 ; Portugal. Fundação para a Ciência e a Tecnologia; PTDC/SAU-PUB/29651/2017 ; Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BD/101060/2014 ; Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BD/12046/2016 ; Deputación Provincial da Coruña; 2019000011550
This article belongs to the Special Issue Toxicity and Ecotoxicity Assessment of Nanomaterials by In Vitro Models ; Titanium dioxide nanoparticles (TiO2 NPs) have a wide variety of applications in many consumer products, including as food additives, increasing the concern about the possible hazards that TiO2 NPs may pose to human health. Although most previous studies have focused on the respiratory system, ingestion must also be considered as an important exposure route. Furthermore, after inhalation or ingestion, TiO2 NPs can reach several organs, such as the liver, brain or lungs. Taking this into consideration, the present study focuses on the uptake and potential genotoxicity (micronuclei induction) of TiO2 NPs on four human cell lines of diverse origin: lung cells (A549), liver cells (HepG2), glial cells (A172) and neurons (SH-SY5Y), using flow cytometry methods. Results showed a concentration-, time- and cell-type- dependent increase in TiO2 NPs uptake but no significant induction of micronuclei in any of the tested conditions. Data obtained reinforce the importance of cell model and testing protocols choice for toxicity assessment. However, some questions remain to be answered, namely on the role of cell culture media components on the agglomeration state and mitigation of TiO2 NPs toxic effects. ; The present work was supported by Xunta de Galicia (reference ED431B 2019/02), NanoBioBarriers (PTDC/MED-TOX/31162/2017) funded by Operational Program for Competitiveness and Internationalisation through European Regional Development Funds (FEDER/FNR) and through national funds by the Portuguese Foundation for Science and Technology (FCT) and NanoLegaTox (PTDC/SAU-PUB/29651/2017) project co-financed by COMPETE 2020, Portugal 2020 and European Union, through FEDER. F.B. are M.J.B. recipients of FCT fellowships (SFRH/BD/101060/2014 and SFRH/BD/12046/2016); V.V. is supported by a Beatriz Galindo Research Fellowship (reference BEAGAL18/00142); and NF-B by a Deputación Provincial da Coruña fellowship (2019000011550). ; info:eu-repo/semantics/publishedVersion
Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591668/pdf/10.1177_2042098619854014.pdf ; Background: The European Union (EU)(7)-PIM (potentially inappropriate medication) list presents the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe; however, several country-specific studies have documented lower specificity of this list on pharmaceutical markets of some countries. The aim of our study was to describe approval rates and marketing of PIMs stated by EU(7)-PIM criteria in six EU countries [in comparison with the American Geriatric Society (AGS) Beers 2015 criteria]. Methods: Research teams of six EU countries (Czech Republic, Spain, Portugal, Serbia, Hungary and Turkey) participated in this study conducted by WG1b EU COST Action IS1402 group in the period October 2015-November 2018. Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drug-regulatory institutes and up-to-date drug compendia. The EU(7)-PIM list and AGS Beers 2015 Criteria (Section 1) were applied. Results: PIMs from EU(7)-PIM list were approved for clinical use more often than those from the AGS Beers 2015 criteria (Section 1). Approval rates for EU(7)-PIMs ranged from 42.8% in Serbia to 71.4% in Spain (for AGS criteria only from 36.4% to 65.1%, respectively). Higher percentages of approved PIMs were documented in Spain (71.4%), Portugal (67.1%) and Turkey (67.5%), lower in Hungary (55.5%), Czech Republic (50.2%) and Serbia (42.8%). The majority of approved PIMs were also currently marketed in all countries except in Turkey (19.8-21.7% not marketed PIMs) and less than 20% of PIMs were available as over-the-counter medications (except in Turkey, 46.4-48.1%). Conclusions: The EU(7)-PIM list was created for utilization in European studies; however, applicability of this list is still limited in some countries, particularly in Eastern and Central Europe. The EU project EUROAGEISM H2020 (2017-2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits. ; This project received funding from the EU COST Action IS1402 initiative 'Ageism: a multi-national, interdisciplinary perspective' (2015–2018), and from the European Union's Horizon 2020 research and innovation program EUROAGEISM H2020 under the Marie Sklodowska-Curie grant agreement no. 764632 (2017–2021). It was also supported by the project INOMED (reg. no. CZ. 02.1.01/0.0/0.0/18_069/0010046): the pre-application research into innovative medicines and medical technologies, cofunded by the EU, by SVV 260 417 and the scientific program PROGRESS Q42 at the Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic. ; info:eu-repo/semantics/publishedVersion
[Abstract] Background: The European Union (EU)(7)-PIM (potentially inappropriate medication) list presents the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe; however, several country-specific studies have documented lower specificity of this list on pharmaceutical markets of some countries. The aim of our study was to describe approval rates and marketing of PIMs stated by EU(7)-PIM criteria in six EU countries [in comparison with the American Geriatric Society (AGS) Beers 2015 criteria]. Methods: Research teams of six EU countries (Czech Republic, Spain, Portugal, Serbia, Hungary and Turkey) participated in this study conducted by WG1b EU COST Action IS1402 group in the period October 2015–November 2018. Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drugregulatory institutes and up-to-date drug compendia. The EU(7)-PIM list and AGS Beers 2015 Criteria (Section 1) were applied. Results: PIMs from EU(7)-PIM list were approved for clinical use more often than those from the AGS Beers 2015 criteria (Section 1). Approval rates for EU(7)-PIMs ranged from 42.8% in Serbia to 71.4% in Spain (for AGS criteria only from 36.4% to 65.1%, respectively). Higher percentages of approved PIMs were documented in Spain (71.4%), Portugal (67.1%) and Turkey (67.5%), lower in Hungary (55.5%), Czech Republic (50.2%) and Serbia (42.8%). The majority of approved PIMs were also currently marketed in all countries except in Turkey (19.8–21.7% not marketed PIMs) and less than 20% of PIMs were available as over-thecounter medications (except in Turkey, 46.4–48.1%). Conclusions: The EU(7)-PIM list was created for utilization in European studies; however, applicability of this list is still limited in some countries, particularly in Eastern and Central Europe. The EU project EUROAGEISM H2020 (2017–2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits. ; European Commision; project INOMED CZ.02.1.01/0.0/0.0/18_069/0010046
Background: The European Union (EU)(7)-PIM (potentially inappropriate medication) list presents the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe; however, several country-specific studies have documented lower specificity of this list on pharmaceutical markets of some countries. The aim of our study was to describe approval rates and marketing of PIMs stated by EU(7)-PIM criteria in six EU countries [in comparison with the American Geriatric Society (AGS) Beers 2015 criteria]. Methods: Research teams of six EU countries (Czech Republic, Spain, Portugal, Serbia, Hungary and Turkey) participated in this study conducted by WG1b EU COST Action IS1402 group in the period October 2015-November 2018. Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drug-regulatory institutes and up-to-date drug compendia. The EU(7)-PIM list and AGS Beers 2015 Criteria (Section 1) were applied. Results: PIMs from EU(7)-PIM list were approved for clinical use more often than those from the AGS Beers 2015 criteria (Section 1). Approval rates for EU(7)-PIMs ranged from 42.8% in Serbia to 71.4% in Spain (for AGS criteria only from 36.4% to 65.1%, respectively). Higher percentages of approved PIMs were documented in Spain (71.4%), Portugal (67.1%) and Turkey (67.5%), lower in Hungary (55.5%), Czech Republic (50.2%) and Serbia (42.8%). The majority of approved PIMs were also currently marketed in all countries except in Turkey (19.8-21.7% not marketed PIMs) and less than 20% of PIMs were available as over-the-counter medications (except in Turkey, 46.4-48.1%). Conclusions: The EU(7)-PIM list was created for utilization in European studies; however, applicability of this list is still limited in some countries, particularly in Eastern and Central Europe. The EU project EUROAGEISM H2020 (2017-2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits.
[Abstract] The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations. ; This article is based upon work from COST Action hCOMET CA15132, supported by COST (European Cooperation in Science and Technology www.cost.eu) - STSM fellowships for Mirta Milić (IMROH, EU 19); IMROH, Zagreb, Croatia, Institute for Medical Research and Occupational Health (IMROH), Zagreb, Croatia, and the Ministry of Science, Education and Sports of the Republic of Croatia (Grant No. 022-0222148-2125) (EU4); Cancer Plan for PestiBG; Grant number: no ENV201401(EU 8, EU9); Italian Ministry of Education, University and Research PRIN 2005, prot. 2005058197 and Cariplo Foundation (Milan, Italy), Rif. Pratica 2007-5810 and Rif. Pratica 2010.2303 (EU 18); Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG 2015/17564). (EU19); European Union Integrated Projects New Generis, 6th Framework Programme, Priority 5: Food Quality and Safety; Newborns and Genotoxic Exposure Risks, FOOD-CT-2005-016320 (EU22); ACT project No. 036APy/09 and No. 005DBB/12 (EU 24); FCT-SFRH/BPD/96196/2013, SFRH/BPD/100948/2014, Portugal (EU 26); MZ 2012/8-UKBA-8; VEGA 1/0703/13, APVV 15-0063 (EU30); Xunta de Galicia (XUGA 10605B98; INCITE08PXIB106155PR; ED481B2016/190-0; Grants ED431B2019/02), Spain (EU 32); Grant 01 173034, Ministry of Education, Science and Technological Development of the Republic of Serbia (EU 42); The Centre for Industrial and Technological Development within National Strategic Consortia for Techical Research (Industrial Research diets and food with specific characteristics for elderly, SENIFOOD); University of Navarra LE/97; Physiopathology of Obesity and Nutrition (CIBER Obn); Carlos III Health Research Institute (CB12/03/30002); Ministerio de Economia y Compatitividad ('Ramón y Cajal' Programme, RYC-2013-14370) of the Spanish Government for personal support (EU 45); the Ministry of Education, Youth and Sports of the Czech Republic project Healthy Aging in Industrial Environment HAIE (CZ.02.1.01/0.0/0.0/16_019/0000798) which is co-financed by the European Union (European Structural and Investment funds; Operation Programme Research, Development and Education); MYES LO 1508 (EU 46); MICRODIAB Study; ClinicalTrials.org (#NCT02231736) (EU 52); The study was funded by the Italian Ministry for Education, University and Scientific Research (MIUR) - Research No. 2005-062547 (EU14, EU53); Projects financed from Serbian Ministry of Education, Science and Technological Development #11146002, #175035, #173034 (EU 54); Mehr foundation organisation, UK (EU 55); MCTI/CNPQ No. 01/2016-Universal; FAPESC No. 09/2015; MEC/MCTI/CAPES/CNPQ/FAPS/ No. 09/2014, Brazil (CSA 6); the National Nuclear Energy Agency of Indonesia (Badan Tenaga Nuklir Nasional) with contract number 080.01.06 3447.001 001.052.A (AS4); Slovak Grant Agency (APVT-21 013202, APVT-21- 017704); Ministry of Health, Slovak Republic (2005/43-SZU-21, 2006/07- SZU-02 MZ SR, 2005/42-SZU-20