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LiCoO2 Particles Used In Li-ion Batteries Induce Primary Mutagenicity In Lung Cells Via Their Capacity To Generate Hydroxyl Radicals

Violaine Sironval, Vittoria Scagliarini, Sivakumar Murugadoss, Maura Tomatis, Yousof Yakoub, Francesco Turci, Peter Hoet, Dominique Lison, Sybille van den Brule

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Abstract Background Li-ion batteries (LIB) are used in most portable electronics. Among a wide variety of materials, LiCoO2 (LCO) is one of the most used for the cathode of LIB. LCO particles induce oxidative stress in mouse lungs due to their Co content, and have a strong inflammatory potential. In this study, we assessed the mutagenic potential of LCO particles in lung cells in comparison to another particulate material used in LIB, LTO (Li4Ti5O12), which has a low inflammatory potential compared to LCO particles. Results We assessed the mutagenic potential of LCO and LTO particles in vitro by performing a cytokinesis-block micronucleus (MN) assay with rat lung epithelial cells (RLE), as well as in vivo in alveolar type II epithelial (AT-II) cells. LCO particles induced MN in vitro at non-cytotoxic concentrations and in vivo at non-inflammatory doses, indicating a primary genotoxic mechanism. LTO particles did not induce MN. Electron paramagnetic resonance and terephthalate assays showed that LCO particles produce hydroxyl radicals (•OH). Catalase inhibits this •OH production. In an alkaline comet assay with the oxidative DNA damage repair enzyme human 8-oxoguanine DNA glycosylase 1, LCO particles induced DNA strand breaks and oxidative lesions. The addition of catalase reduced the frequency of MN induced by LCO particles in vitro. Conclusions We report the mutagenic activity of LCO particles used in LIB in vitro and in vivo. Our data support the role of Co(II) ions released from these particles in their primary genotoxic activity which includes the formation of •OH by a Fenton-like reaction, oxidative DNA lesions and strand breaks, thus leading to chromosomal breaks and the formation of MN. Documenting the genotoxic potential of the other LIB particles, especially those containing Co and/or Ni, is therefore needed to guarantee a safe and sustainable development of LIB.