Investigating Lithium Nickel Manganese Cobalt Oxide's Mechanism of Toxicity in Caenorhabditis elegans

Abstract

In recent years, the demand for lithium-ion batteries (LIB) for electronics has increased. The scientific literature on the toxicity of these lithium compounds is limited, and it relates mainly to measured organismal endpoints rather than mechanisms of toxicity. This master's project investigated a proposed adverse outcome pathway (AOP) for one important lithium compound, LiNi0.33Mn0.33Co0.33O2 (NMC) in the Caenorhabditis elegans model, using more mechanistic methods than have been reported in the literature. The measured endpoints were the estimation of altertions to the oxidized to reduced glutathione ratio as a measure of cellular redox state, ATP levels, and growth, for wild-type worms and worms with knockdowns of the human disease genes frh-1 and gas-1, which encode proteins involved in energy production and redox state regulation. The main results were that several lithium compounds caused growth inhibition only at levels of exposure that appear to be high relative to likely environmental concentration; lithium did not significantly impact the redox state, and there is no substantial evidence that ATP levels were decreased at levels of exposure that caused mild growth inhibition, and growth inhibition was not altered by frh-1 and gas-1 knockdown in a way consistent with the proposed AOP. The main conclusion is that, in C. elegans, growth inhibition is not likely caused by increased redox stress or ATP decrease, suggesting an alternative mechanism of toxicity.