Abstract
BackgroundLi-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2 (LCO), one of the most used cathode material, induces inflammatory and fibrotic lung responses in mice. LCO also stabilizes hypoxia-inducible factor (HIF) -1α, a factor implicated in inflammation, fibrosis and carcinogenicity. Here, we investigated the role of cobalt, nickel and HIF-1α as determinants of toxicity, and evaluated their predictive value for the lung toxicity of LIB particles in in vitro assays.ResultsBy testing a set of 5 selected LIB particles (LCO, LiNiMnCoO2, LiNiCoAlO2) with different cobalt and nickel contents, we found a positive correlation between their in vivo lung inflammatory activity, and (i) Co and Ni particle content and their bioaccessibility and (ii) the stabilization of HIF-1α in the lung. Inhibition of HIF-1α with chetomin or PX-478 blunted the lung inflammatory response to LCO in mice. In IL-1β deficient mice, HIF-1α was the upstream signal of the inflammatory lung response to LCO. In vitro, the level of HIF-1α stabilization induced by LIB particles in BEAS-2B cells correlated with the intensity of lung inflammation induced by the same particles in vivo.ConclusionsWe conclude that HIF-1α, stabilized in lung cells by released Co and Ni ions, is a mechanism-based biomarker of lung inflammatory responses induced by LIB particles containing Co/Ni. Documenting the Co/Ni content of LIB particles, their bioaccessibility and their capacity to stabilize HIF-1α in vitro can be used to predict the lung inflammatory potential of LIB particles.
Highlights
Li-ion batteries (LIB) are increasingly used worldwide
Contrasting lung toxicity of LIB particles We first documented the dose-responses for lung inflammatory and fibrotic responses induced by LCO
hypoxia-inducible factor (HIF)-1α mediates lung inflammation induced by LCO We evaluated the implication of HIF-1α in the toxic activity of LIB particles by inhibiting its activity with chetomin, a disrupter of HIF binding to its transcriptional co-activator P300 [16]
Summary
Li-ion batteries (LIB) are increasingly used worldwide. They are made of low solubility micrometric particles, implying a potential for inhalation toxicity in occupational settings and possibly for consumers. LiCoO2 (LCO), one of the most used cathode material, induces inflammatory and fibrotic lung responses in mice. LCO stabilizes hypoxia-inducible factor (HIF) -1α, a factor implicated in inflammation, fibrosis and carcinogenicity. We previously assessed the lung toxicity of three commonly used LIB particles, lithium iron phosphate (LiFePO4/LFP), lithium titanium oxide (Li4Ti5O12/LTO) and lithium cobalt oxide (LiCoO2/LCO), and concluded that they represent a respiratory hazard independently of their Li content [5]. Long-term inflammation was maintained after LFP and LCO, and only LCO induced fibrotic responses. Increased hypoxia-inducible factor (HIF)-1α was recorded in the lung of mice exposed to LCO.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have