Respiratory Exposure to Lithium Nickel Manganese Cobalt Oxide Particles: Evidence for Toxicity and Disruption of Metal Homeostasis in Mice

Lithium nickel manganese cobalt oxide (NMC) is a widely used cathode material in lithium-ion batteries. However, its increasing utilization has raised concerns about environmental contamination and potential health risks, underscoring the need for comprehensive toxicological assessments. In this study, we evaluated the tissue distribution and toxicological effects of NMC in adult male C57BL/6J mice following 28-day intratracheal instillation at doses of 32.5, 162.5, and 325 μg/kg/day. Our findings demonstrated that lithium primarily accumulated in the heart, while nickel also showed high accumulation ability in the heart, followed by the liver and epididymis. Cobalt accumulated predominantly in the spleen, kidneys, and epididymis, whereas manganese was mainly concentrated in the epididymis. Notably, exposure to high doses of NMC resulted in a reduction in body weight, elevated levels of systemic inflammation biomarkers, and significant histopathological changes. These histopathological alterations included alveolar fusion and structural damage in the lungs, loss of distinction between red and white pulp in the spleen, renal tubular dilation, and a decrease in spermatogenic cells in the testes and epididymis. Furthermore, NMC exposure disrupted the homeostasis of trace metals (copper, vanadium, molybdenum, strontium, selenium, and stannum) in mice, suggesting their potential roles in NMC-induced toxicity. This study provides a detailed characterization of the distribution and toxic effects of low-dose NMC exposure, contributing valuable data for the toxicology evaluation of NMC materials.