As an organochlorine insecticide, endosulfan has been widely banned or 
restricted, but it is still largely used in many developing countries. Previous 
studies have shown multiple adverse health effects of endosulfan. However, the 
neurotoxicity of endosulfan has not been fully elucidated. In this study, 
endosulfan isomers (α-/β-endosulfan) and their major metabolites (endosulfan 
sulfate, endosulfan diol, and endosulfan lactone) were, respectively, exposed to 
human neuroblastoma SH-SY5Y cells. Results showed that both α-endosulfan and 
β-endosulfan caused decrease of cell viability and morphological damages in a 
dose-dependent manner. Their median effective concentrations (EC50s) were 
respectively 79.6 μM (α-endosulfan) and 50.37 μM (β-endosulfan) for 72 h 
exposure. EC50s of α/β-endosulfan mixture were lower than that of the single 
isomer. However, EC50s of its metabolites were higher than that of technical 
endosulfan. Endosulfan and its metabolites caused increases of reactive oxygen 
species and the lipid peroxidation, but decrease of superoxide dismutase in a 
dose-dependent manner. These results indicate that α-endosulfan exhibits higher 
neurotoxicity than β-endosulfan. Mixture of endosulfan isomers shows stronger 
cytotoxicity than the single isomer. After endosulfan is degraded, cytotoxicity 
of its metabolites decreases gradually. The neurotoxicity of endosulfan and its 
metabolites is closely related to oxidative damage and antioxidative deficit.