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MAMMALIAN CELL CYTOTOXICITY AND GENOTOXICITY OF NEW DRINKING WATER DISINFECTION BY-PRODUCTS
Citation:
Plewa, M. J., E. D. Wagner, A. C. Kim, R. Nelson, AND S D. Richardson. MAMMALIAN CELL CYTOTOXICITY AND GENOTOXICITY OF NEW DRINKING WATER DISINFECTION BY-PRODUCTS. Presented at 2003 Environmental Mutagen Society Conference, Miami, FL, May 10-14, 2003.
Impact/Purpose:
(1) Use toxicity-based approach to identify DBPs that show the greatest toxic response. (2) Comprehensively identify DBPs formed by different disinfectant regimes for the 'Four Lab Study'. (3) Determine the mechanisms of formation for potentially hazardous bromonitromethane DBPs.
Description:
The disinfection of drinking water continues to protect the public health against acute disease. Drinking water disinfection by-products (DBPs) are formed by the reaction of a disinfectant with naturally occurring organic matter. Many DBPs are genotoxic and are implicated as human carcinogens and teratogens. Two new DBPs, 2,3,5-tribromopyrrole (TBP) and iodoacetic acid (IA) were isolated and chemically characterized. TBP was isolated from chlorine dioxide-chlorine and chlorine dioxide-chloramine treated water from the Sea of Galilee, Israel, that contained bromide levels of approximately 2 mg/L. This is the first time a halopyrrole has been identified as a DBP. Using a microplate-based chronic cytotoxicity assay, TBP was a strong cytotoxin in Chinese hamster ovary (CHO) cells. The concentration of TBP that reduced the CHO cell density by 50% (%C?) after 72 h exposure was 60.6 microM. At concentrations above 150 microM, TBP induced genomic DNA damage in CHO cells treated for 4 h using the single cell gel electrophoresis (SCGE comet) assay. IA was identified in chloramine-treated drinking water from Texas, U.S.A. that contained bromide levels of 0.25 mg/L. IA is a very potent CHO cell chronic cytotoxin with a %C? value of 2.9 microM. IA is also the strongest genotoxic agent of the 22 DBPs we have analyzed. IA at concentrations of 5 microM and above after 4 h exposure induced genomic DNA damage in CHO cells. For the monohalogenated acetic acids the rank order, from high to low toxicity, for both CHO cell chronic cytotoxicity and acute genotoxicity was iodoacetic acid > bromoacetic acid >> chloroacetic acid.