Multi-organ toxicity induced by subacute inhalation exposure to rotenone in mice

Rotenone is one of the most widely used botanical insecticides. During spraying and residue formation, it can create aerosols that enter the human body through the respiratory tract, posing significant environmental exposure risks. However, the toxicological mechanisms targeting specific organs after inhalation remain unclear, and research on multi-organ toxicity is currently lacking. This study employed in vivo experimental methods to establish an animal model simulating low-dose inhalation exposure scenarios. Mice were exposed to 0.5 h of daily inhalation of rotenone for 28 d at concentrations of 0.36, 3.6, and 5 mg/m³. Histopathological analysis revealed that rotenone exposure exerted toxic effects in the mice lung, brain, and ovarian tissues. The pro-inflammatory factors, tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-2 (IL-2) were significantly elevated in both the brain and lung. The most significant increase in TNF-α levels was observed in brain tissue from the rotenone-treated group (214.52-381.31%). In addition, rotenone exposure reduced alpha diversity of lung microbiota and significantly (***, p ≤ 0.001) increased secretion of endocrine hormones (estradiol, progesterone, and testosterone). This study provides systematic evidence for rotenone-induced multi-organ toxicity following inhalation exposure, offering a new perspective for assessing the health risks of airborne pesticide residues.