Assessment of in vitro and in vivo Toxicity Induced by Manganese Dioxide Submicron Particles (MnO sub(2)-SMPs)

Abstract

The utilization of manganese dioxide (MnO sub(2)) submicron particles (SMPs) in various industrial and biomedical applications has raised concerns regarding their impact on human health and the environment. This study aimed to assess the toxicological implications of a potential mosquito larvicide: MnO sub(2)-SMPs (200-400 nm size), synthesized via a redox method, in an in vitro model (fish hepatocytes) and in vivo model (Swiss Albino mice). Primary liver cells of Oreochromis mossambicus were cultured and exposed to varying concentrations of MnO sub(2)-SMPs. Cytotoxicity analyzed using the MTT assay, revealed a concentration- and time-dependent decrease in cell viability. In vivo, the SMPs were evaluated after 14 days of repeated oral administration in mice at two different doses (100 mg/kg and 500 mg/kg). The SMPs induced minor but statistically significant alterations in biochemical, antioxidant, and histopathological parameters in mice. The lowest concentration of 100 mg/kg induced alterations in only a few biochemical parameters and this has been proposed as the LOAEL for MnO sub(2)-SMPs in this study. Multivariate PERMANOVA analysis revealed significant differences across dose groups, while traditional univariate tests identified only a subset of these changes, highlighting the importance of comprehensive biomarker evaluations. These findings provide fundamental insights into the hepatotoxic and nephrotoxic potential of MnO sub(2)-SMPs.