A pan-European infrastructure for quality in nanomaterials safety testing

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Fibrous shape underlies the mutagenic and carcinogenic potential of nanosilver while surface chemistry affects the biosafety of iron oxide nanoparticles

Publication . Gábelová, A.; El Yamani, N.; Alonso, T.I.; Buliaková, B.; Srančíková, A.; Bábelová, A.; Pran, E.R.; Fjellsbø, L.M.; Elje, E.; Yazdani, M.; Silva, M.J.; Dušinská, M.

Nowadays engineered nanomaterials (ENMs) are increasingly used in a wide range of commercial products and biomedical applications. Despite this, the knowledge of human potential health risk as well as comprehensive biological and toxicological information is still limited. We have investigated the capacity of two frequently used metallic ENMs, nanosilver and magnetite nanoparticles (MNPs), to induce thymidine kinase (Tk+/−) mutations in L5178Y mouse lymphoma cells and transformed foci in Bhas 42 cells. Two types of nanosilver, spherical nanoparticles (AgNM300) and fibrous (AgNM302) nanorods/wires, and MNPs differing in surface modifications [MNPs coated with sodium oleate (SO-MNPs), MNPs coated with SO + polyethylene glycol (SO-PEG-MNPs) and MNPs coated with SO + PEG + poly(lactide-co-glycolic acid) SO-PEG-PLGA-MNPs] were included in this study. Spherical AgNM300 showed neither mutagenic nor carcinogenic potential. In contrast, silver nanorods/wires (AgNM302) increased significantly the number of both gene mutations and transformed foci compared with the control (untreated) cells. Under the same treatment conditions, neither SO-MNPs nor SO-PEG-PLGA-MNPs increased the mutant frequency compared with control cells though an equivocal mutagenic effect was estimated for SOPEG- MNPs. Although SO-MNPs and SO-PEG-MNPs did not show any carcinogenic potential, SO-PEG-PLGA-MNPs increased concentration dependently the number of transformed foci in Bhas 42 cells compared with the control cells. Our results revealed that fibrous shape underlies the mutagenic and carcinogenic potential of nanosilver while surface chemistry affects the biosafety of MNPs. Considering that both nanosilver and MNPs are prospective ENMs for biomedical applications, further toxicological evaluations are warranted to assess comprehensively the biosafety of these nanomaterials.

2016-09-22Journal article

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Contribution to the hazard assessment of benchmark metallic nanomaterials through a set of in vitro genotoxicity assays

Publication . Vital, Nádia; El Yamani, Naouale; Pinhão, Mariana; Rúden-Pra, Elise; Louro, Henriqueta; Dušinská, Maria; Silva, Maria João

Background and Aim: Metall-based nanomaterials (NMs) are among the most commonly applied manufactured nanomaterials (NM). Regardless of the considerable efforts to assess their safety, the presently available data do not allow for general and consistent conclusions. Moreover, the validity of the classical in vitro testing systems for NMs hazard assessment has been questioned and needs confirmation. The present study aimed at evaluating the toxicity of three benchmark metallic NMs - titanium dioxide (NM-100),cerium dioxide (NM-212) and nanosilver - with different physicochemical properties, using a battery of in vitro genotoxicity assays, in an attempt to characterize their toxicity profile.

2018-03-19Conference object

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Hazard Assessment of Benchmark Metal-Based Nanomaterials Through a Set of In Vitro Genotoxicity Assays

Publication . Vital, Nádia; Pinhão, Mariana; Yamani, Naouale El; Rundén-Pran, Elise; Louro, Henriqueta; Dušinská, Maria; Silva, Maria João

For safety assessment of nanomaterials (NMs), in vitro genotoxicity data based on welldesigned experiments is required. Metal-based NMs are amongst the most used in consumer products. In this chapter, we report results for three metal-based NMs, titanium dioxide (NM- 100), cerium dioxide (NM-212) and silver (NM-302) in V79 cells, using a set of in vitro genotoxicity assays covering different endpoints: the medium-throughput comet assay and its modified version (with the enzyme formamidopyrimidine DNA glycosylase, Fpg), measuring DNA strand beaks (SBs) and oxidized purines, respectively; the micronucleus (MN) assay, assessing chromosomal damage; and the Hprt gene mutation test. The results generated by this test battery showed that all NMs displayed genotoxic potential. NM-100 induced DNA breaks, DNA oxidation damage and point mutations but not chromosome instability. NM-212 increased the level of DNA oxidation damage, point mutations and increased the MN frequency at the highest concentration tested. NM-302 was moderately cytotoxic and induced gene mutations, but not DNA or chromosome damage. In conclusion, the presented in vitro genotoxicity testing strategy allowed the identification of genotoxic effects caused by three different metal-based NMs, raising concern as to their impact on human health. The results support the use of this in vitro test battery for the genotoxicity assessment of NMs, reducing the use of more expensive, time-consuming and ethically demanding in vivo assays, in compliance with the 3 R’s.

2022Book part

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Contribution to the hazard assessment of benchmark metallic nanomaterials through a set of in vitro genotoxicity assays

Publication . Vital, Nádia; El Yamani, Naouale; Pinhão, Mariana; Rúden-Pra, Elise; Louro, Henriqueta; Dušinská, Maria; Silva, Maria João

Metallic nanomaterials are among the most commonly applied manufactured nanomaterials (NM). Regardless of the considerable efforts to assess their safety, the presently available data do not allow for general and consistent conclusions. Moreover, the validity of the classical in vitro testing systems for NMs hazard assessment has been questioned and needs confirmation. In the present study, the toxicity of three benchmark metallic NMs, including two insoluble NMs - titanium (NM-100) and cerium (NM-212) dioxides - and soluble silver nanorods/wires (NM-302) was investigated. A panel of in vitro genotoxicity tests that analyze different endpoints was applied and the physico-chemical properties of each NM were considered.

2018-03-20Conference object

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