Neurobehavioral and Systemic Toxicity of Sub-Chronic Transfluthrin Exposure in Rats: An Exploratory In Vivo Study

Abstract Background: Transfluthrin,a fast-acting synthetic pyrethroid widely used in household insecticides, associated with potential neurotoxic and systemic health effects. Objective: This study aimed to evaluate the sub-chronic effects of transfluthrin exposure via oral and inhalation routes on neurobehavior, systemic toxicity, and muscarinic acetylcholine receptor (mAchR) gene expression in rats. Methods: Adult male Sprague Dawley rats were exposed to transfluthrin for 90 days either orally (500 ppm in chow) or via inhalation (0.88% transfluthrin vaporizers, 12 h/day). Neurobehavioral assessments were performed using the Elevated Plus Maze (EPM), Open Field Test (OFT), and Morris Water Maze (MWM). Hematological and biochemical parameters were measured, and histopathological analysis of lung and liver tissues was conducted. mAchR gene expression was evaluated via quantitative RT-PCR, and blood transfluthrin levels were quantified using gas chromatography-mass spectrometry (GC-MS). Results: Transfluthrin-exposed rats exhibited significantly increased anxiety-like behavior (p=0.003), hyperactivity (p=0.04), and impaired spatial learning and memory (p=0.04). Elevated levels of liver enzymes alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and renal markers (urea, creatinine) indicated systemic toxicity. Histopathological findings included hepatic dysplastic foci and pulmonary inflammation.Additionally, a non-significant downward trend in mAChR gene expression was observed in exposed groups.Transfluthrin was detected in the bloodstream following both exposure routes, with significantly higher concentrations in orally exposed rats. Conclusion: Sub-chronic transfluthrin exposure induces neurobehavioral impairments, systemic toxicity, and organ damage in rats. While mAChR downregulation may contribute to cognitive deficits, further mechanistic studies are needed. Considering the widespread domestic use of transfluthrin, these findings underscore the need for comprehensive toxicological evaluations to inform public health policies.