Water reuse is receiving unprecedented attention as many areas around the globe attempt to better-manage their fresh water resources. Wastewaters in coastal regions may contain elevated levels of bromide (Br-) and iodide (I-) from seawater intrusion or high mineral content in the source waters. Disinfection of such wastewater is essential to prevent the spread of pathogens; however, little is known about the toxicity of the treated wastewater. In this study, we evaluated the genotoxicity to Chinese hamster ovary (CHO) cells induced by municipal secondary wastewater effluent amended with elevated Br- and I- after disinfection by chlorine, chloramines, or ozone. We calibrated and applied an N-acetylcysteine (NAC) thiol reactivity assay as a surrogate for thiol reactivity with biological proteins (glutathione) of wastewater samples. Chlorination of wastewaters produced CHO cell genotoxicity comparable to chloramination, 3.9 times more genotoxic than the nondisinfected controls. Ozonated wastewater was at least 3 times less genotoxic than the samples treated with chlorine-based disinfectants and was not significantly different compared with the nondisinfected controls. Positive and significant correlations were observed among genotoxicity, cytotoxicity, and NAC thiol reactivity for all disinfected samples. These results indicate that the ozonation of wastewater with high Br- and I- levels may yield organics with lower genotoxicity to CHO cells than chlorine-based disinfection. NAC thiol reactivity, although excluding the possible effect of bromate from ozonation in this work, could be used as a rapid in chemico screen for potential genotoxicity and cytotoxicity in mammalian cells exposed to disinfected wastewaters.