SUBACUTE EXPOSURE TO A COMMERCIAL S-METOLACHLOR/FLUMIOXAZIN FORMULATION INDUCES SYSTEMIC, GENOTOXIC, AND REDOX ALTERATIONS IN WISTAR RATS.

Abstract

This study investigated the systemic, genotoxic, and brain redox effects of subacute exposure to a commercial herbicide formulation containing S-metolachlor and flumioxazin (Apresa®) in male and female Wistar rats using a repeated-dose design based on OECD Test Guideline 407. Animals received oral doses of 250, 500, or 1,000 mg/kg/day for 28 consecutive days. Sialorrhea was observed in both sexes at all tested doses, whereas reduced body weight gain occurred in males receiving 500 and 1,000 mg/kg. Treatment-related increases in relative liver and kidney weights were also observed, although their morphological basis and toxicological significance could not be established in the absence of histopathological evaluation. Bone marrow micronucleus frequency increased in males exposed to 1,000 mg/kg, indicating a sex-dependent genotoxic response at the highest tested dose. Repeated exposure also altered oxidative damage markers and antioxidant enzyme activities in the cerebral cortex, striatum, and hippocampus, providing evidence of disrupted redox homeostasis across the evaluated brain regions. However, because behavioral, functional, and brain histopathological endpoints were not assessed, these biochemical alterations should not be interpreted as direct evidence of neurotoxicity. Overall, repeated exposure to the commercial formulation elicited systemic and genotoxic effects and disrupted redox homeostasis under the tested experimental conditions. Because the complete formulation was administered, the observed effects cannot be attributed specifically to S-metolachlor, flumioxazin, co-formulants, or interactions among formulation components.