title: Evaluation of the cytotoxic and genotoxic effects of benchmark multi-walled carbon nanotubes in relation to their physicochemical properties.
abstract: To contribute with scientific evidence to the grouping strategy for the safety assessment of multi-walled carbon nanotubes (MWCNTs), this work describes the investigation of the cytotoxic and genotoxic effects of four benchmark MWCNTs in relation to their physicochemical characteristics, using two types of human respiratory cells. The cytotoxic effects were analysed using the clonogenic assay and replication index determination. A 48h-exposure of cells revealed that NM-401 was the only cytotoxic MWCNT in both cell lines, but after 8-days exposure, the clonogenic assay in A549 cells showed cytotoxic effects for all the tested MWCNTs. Correlation analysis suggested an association between the MWCNTs size in cell culture medium and cytotoxicity. No induction of DNA damage was observed after any MWCNTs in any cell line by the comet assay, while the micronucleus assay revealed that both NM-401 and NM-402 were genotoxic in A549 cells. NM-401 and NM-402 are the two longest MWCNTs analyzed in this work, suggesting that length may be determinant for genotoxicity. No induction of micronuclei was observed in BBEAS-2Beas-2B cell line and the different effect in both cell lines is explained in view of the size-distribution of MWCNTs in the cell culture medium, rather than cell's specificities.
authors.affiliation: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal; Toxicogenomics and Human Health (ToxOmics), Nova Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal; PToNANO, Lisbon, Portugal. Electronic address: henriqueta.louro@insa.min-saude.pt.
authors.forename: Henriqueta
authors.initials: H
authors.lastname: Louro
authors.affiliation: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal; Toxicogenomics and Human Health (ToxOmics), Nova Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal; PToNANO, Lisbon, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Pinhão
authors.affiliation: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal; PToNANO, Lisbon, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Santos
authors.affiliation: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Tavares
authors.affiliation: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal; PToNANO, Lisbon, Portugal; ISQ - Instituto de Soldadura e Qualidade, Taguspark, Oeiras, Porto Salvo, Portugal.
authors.forename: Nádia
authors.initials: N
authors.lastname: Vital
authors.affiliation: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal; Toxicogenomics and Human Health (ToxOmics), Nova Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal; PToNANO, Lisbon, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Silva
mesh_terms: D019985:Benchmarking; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D055598:Chemical Phenomena; D020552:Comet Assay; D004249:DNA Damage; D006801:Humans; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size
chemical_list: D009153:Mutagens; D037742:Nanotubes, Carbon
keywords: Carbon nanotubes; Cytotoxicity; Genotoxicity; Physicochemical characteristics