Lithium Nickel Manganese Cobalt Oxide Particles Cause Developmental Neurotoxicity in Caenorhabditis elegans

Lithium is increasingly used in rechargeable batteries for mobile devices, electric vehicles, and energy storage, among other applications. One of the common formulations of lithium batteries is lithium nickel manganese cobalt oxide (LiNMC) particles. Increasing utilization of LiNMC batteries would require adequate disposal and/or recycling, and yet the potential disposal of lithium batteries as waste either in or outside of landfills might lead to toxic effects to people and wildlife. However, understanding of the potential toxicity of LiNMC particles is limited. Based on previous literature investigating the mechanisms of toxicity of the constituent metals, as well as lithium cobalt oxide (LCO) nanoparticles, we hypothesized that LiNMCs would cause toxicity via mitochondrial impairment and oxidative stress. We further hypothesized that LiNMC toxicity would be exacerbated by knockdown of frh-1 and gas-1, Caenorhabditis elegans orthologs of human mitochondrial disease genes frataxin and NDUFS2. Finally, we predicted that LiNMC exposure would cause developmental neurotoxicity. We tested these predictions by carrying out LiNMC exposures, and found these did not significantly impact the redox state, steady-state ATP levels, mitochondrial:nuclear DNA ratio, or oxygen consumption in worms exposed developmentally to amounts of LiNMC that caused mild growth inhibition. We discuss possible reasons for the difference between our results and previous publications, including particle size. Furthermore, while knockdown of frh-1 and gas-1 altered several parameters, knockdown of these genes did not increase or decrease the effects of LiNMCs. However, we did find that exposure to LiNMC caused degeneration of dopaminergic, cholinergic, glutamatergic, and GABAergic neurons, but not serotonergic neurons or glial cells. Interestingly, it appears that the developmental neurotoxicity was driven either by a particle-specific effect, or a component other than lithium, because exposure to lithium chloride at the same concentration had no effect.