COMPARATIVE MAMMALIAN CELL CHRONIC CYTOTOXICITY OF CYANOGEN HALIDE DRINKING WATER DISINFECTION BYPRODUCTS

摘要

With the U.S. EPA Stage 2 D/DBP Rule the increased use of chloramination in the disinfection of surface waters is predicted. Cyanogen chloride (CICN) and other cyanogen halides are toxic disinfection byproducts (DBPs) commonly found in chloraminated drinking water. Using an in vitro chronic mammalian cell cytotoxicity assay we are analyzing CICN, cyanogen bromide (BrCN), cyanogen iodine (ICN) and N-chloroaminomethanol (CH2(OH)NHCI). The microplate cytotoxicity assay measures the reduction in density of Chinese hamster ovary (CHO) cells as a function of DBP concentration over a 72 h period (three cell generations). Over 65 DBPs have been analyzed with this assay with responses over a concentration range of 6 log orders. CICN, BrCN, ICN and CH2(OH)NHCI are being analyzed in a concentration range from 500 nM to 1 mM. For each agent the cytotoxicity concentration-response curve will be generated with 10 concentrations and 16 replicates per concentration. We will conduct regression analysis and calculate the concentration that induces a cell density that is 50% of the negative control. This value, the %C1/2 value, is analogous to the LC_(50) value. The cytotoxicity data of these agents will be compared to other DBPs analyzed with this assay to determine their relative cytotoxic potency. In addition, a structure function relationship (SAR) analysis of the effect of the halogen on the biological activity will be conducted. These data will add to the database on the mammalian cell toxicity of DBPs.