Dose-dependent cholinergic, inflammatory, and genotoxic effects of etoxazole in female Wistar rats

Etoxazole is a widely used oxazoline acaricide in agriculture; however, its toxicological profile in mammalian systems remains insufficiently characterized. This study investigated the dose-dependent effects of subchronic etoxazole exposure on serum biochemical, genotoxic, and haematological parameters in female Wistar rats administered 25, 100, 250, 500, or 750 mg/kg by oral gavage for 28 days. Body weight, feed and water consumption were monitored weekly, and acetylcholinesterase (AChE), butyrylcholinesterase (BChE), adenosine deaminase (ADA), myeloperoxidase (MPO), and oxidative DNA damage (8-OHdG) were evaluated as biochemical parameters in serum, liver, and kidney tissues, while haematological indices (WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, and differential counts) were assessed from peripheral blood. AChE and BChE activities decreased in a dose-dependent manner, with significant inhibition observed at doses of 250 mg/kg and above across all three biological compartments ( p < 0.05); notably, serum AChE inhibition was detectable at the lowest dose tested. ADA and MPO activities were significantly elevated at 250 mg/kg and above ( p < 0.05), indicating enhanced inflammatory activity and oxidative stress. DNA damage increased progressively with dose and was particularly pronounced in the ETX500 and ETX750 groups, with renal tissue displaying significant genotoxic effects even at the lowest dose examined. High-dose exposure was further associated with leukocytosis, erythrocytic alterations, and reduced feed and water intake, while body weight gain was maintained across all groups without statistically significant intergroup differences. These findings collectively demonstrate dose-dependent inhibition of cholinesterase activity, consistent with altered cholinergic homeostasis, alongside oxidative-inflammatory and genotoxic effects in rats, identifying the liver and kidney as primary biochemical target compartments — as indicated by enzymatic and genotoxic markers — and highlighting the need for more comprehensive mammalian toxicological assessment of this compound.