Organochlorine pesticide acetofenate and its hydrolytic metabolite in rabbits: Enantioselective metabolism and cytotoxicity

Abstract Acetofenate (AF) is a chiral organochlorine pesticide used for controlling hygiene pests. In this study, the metabolism of AF in rabbits in vivo and in vitro was investigated and the primary chiral metabolite acetofenate-alcohol (AF-A) was analyzed. The cytotoxicity of AF and AF-A was also determined. AF in rabbits in vivo was eliminated so rapidly that AF could not be detected within 10 min after intravenous administration at 20 mg/kg (body weight), and AF-A was quickly formed. In vitro metabolism assay, using plasma and liver microsomes, showed that AF was also quickly metabolized to AF-A and the metabolic process was significantly enantioselective with preferential degradation of (-)-AF and formation of (-)-AF-A. The cytotoxicity of AF and AF-A were investigated by assessing cell proliferation, apoptosis and generation of reactive oxygen species. The results showed that AF and AF-A induce enantioselective cytotoxicity. This study will be helpful for improving knowledge about the metabolism and toxicity of AF on an enantiomeric level and providing evidence to understand the potential environmental risk.