Efficacy of Haloxyfop-R-Methyl on Allium cepa: Cyto-Genotoxic and In Silico Docking Studies on the Mechanism of Action.

Haloxyfop-R-methyl (HRM) is extensively employed to control annual and perennial grass weeds. This study aimed to investigate the cyto-genotoxic effects of HRM at concentrations of 1.19, 2.38, and 4.76 mg/L over various time intervals (24, 48, 72, and 96 h) on Allium cepa root. Parameters including root growth, mitotic index (MI), chromosomal aberrations (CAs), and DNA damage were assessed using root growth inhibition, A. cepa ana-telophase, and alkaline comet assays. Moreover, to gain molecular insights into the cyto-genotoxic effects of HRM as well as the active agent haloxyfop-R (HR), molecular docking was performed against two intracellular target receptors: the carboxyltransferase (CT) domain of yeast acetyl-CoA carboxylase (ACC) and a double-stranded DNA dodecamer. The root growth inhibition test revealed a statistically significant reduction in onion root length, from 3.64 ± 0.18 cm at lower concentrations to 0.05 ± 0.02 cm at higher concentrations of HRM. A significant decrease in the MI was observed at all treatment periods, except at 1.19 mg/L after 72 h, along with an increase in CAs during the 24 and 48 h applications, except at 4.76 mg/L after 48 h, in A. cepa root cells treated with HRM, compared to the negative control group. DNA damage increased with HRM exposure and was found to be both concentration-and time-dependent. Docking studies revealed strong binding interactions of HRM and HR with the CT domain of the ACC enzyme, which is a central player in fatty acid biosynthesis, and showed that both HRM and HR bound specifically to DNA minor groove regions rich in GC bases. The current study confirmed the cyto-genotoxic effects of HRM. Its use should be carefully regulated, as it may present ecological risks by negatively impacting the genomes of non-target organisms.