On assessing the potential risk of dose-dependent hepatotoxic effects of selenium oxide nanoparticles

Selenium nanoparticles (Se NPs) have found wide application in many human economic activities. Therefore, it is necessary to predict and assess emerging potential health risks. Nanotoxicants can affect the body causing negative effects that have a non-linear dependence on the dose of a toxic substance. There is no consensus on the LD50 of Se NPs. Recent data on the dose-dependent liver response to different exposures of selenium nanoparticles are contradictory. The aim is to study and characterize potentially adverse dose-dependent effects in the liver under exposure to selenium oxide nanoparticles in a subchronic experiment using mathematical models. Exposure was modeled on male rats aged 3 to 4 months, 12 animals in each group. We used three levels of selenium nanoxide doses for subchronic exposure: 3.6, 18, and 36 mg/kg. The research was approved by the Local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (Protocol No. 2 of April 20, 2021). We observed an atypical dose-response relationship between selenium nanooxide exposure and hepatic changes. The negative effects included pronounced changes in mitochondria of liver cells as well as an imbalance of blood enzymes and cellular composition of the liver, which may indicate damage to the organ and impaired secretory functions following the exposure to low and moderate concentrations of SeO nanoparticles. Our findings can be used for determining chemical safety standards for selenium oxide nanoparticles and assessing their health risks.