Genotoxicity and Occurrence Assessment of Disinfection By-Product Mixtures in Drinking WaterEPA Grant Number: R825956
Title: Genotoxicity and Occurrence Assessment of Disinfection By-Product Mixtures in Drinking Water
Investigators: Minear, Roger A. , Plewa, Michael J.
Institution: University of Illinois at Urbana-Champaign
EPA Project Officer: Nolt-Helms, Cynthia
Project Period: September 1, 1997 through August 31, 2000 (Extended to November 16, 2001)
Project Amount: $378,088
RFA: Drinking Water (1997) RFA Text | Recipients Lists
Research Category: Water , Drinking Water
The general hypothesis asks if the single cell gel electrophoresis (SCG COMET) assay using transgenic mammalian cells can predict human risks from drinking water disinfection by-products (DBPs) rather than bacterial genotoxicity tests and is it sufficiently responsive to evaluate DBPs produced from different disinfection processes and under different conditions? The hypothesis is founded on the premise that mammalian cells may be more representative of direct cytotoxic and genotoxic affects from DBPs on humans than the "traditional" bacterial assays. The objectives of the proposed research are to: (i) calibrate S. typhimurium and transgenic mammalian cells genotoxicity assays using regulated DBPs; (ii) compare the relative genotoxicities of chlorinated versus brominated DBPs; (iii) compare the relative genotoxicities of chlorination by-products (CBPs) versus brominated ozonation by-products (OBPs); (iv) compare the relative genotoxicities of DBPs derived from singular versus combination (sequential) use of ozonation and chlorination; and (v) provide a DBP occurrence data base for extrapolating genotoxicity results to current disinfection practice.
Representative DBPs will be produced from organic matter isolated from a series of representative source waters used for drinking water supplies using both chlorination and ozonation in laboratory reactors under a range of disinfection conditions. Selective conditions will allow differential evaluation of brominated DBPs via ozonation of bromide containing waters and also provide information on the relationship of toxicity to DBP molecular weight. Bulk DBPs will be analyzed for toxicity and mutation induction in S. typhimurium using a suspension test ? S9 (mammalian microsomal metabolic activation). The same DBPs will be analyzed with transgenic Chinese hamster lung cells ? S9 using the single cell gel electrophoresis (SCG) method to detect direct genomic DNA damage. The cytotoxicity of each sample will be determined using a microtiter well technique. The relative genetic damage per unit mass of each DBP sample will be calculated and rank ordered. The level of correlation of the DBP-induced genetic damage will be correlated both qualitatively and quantitatively with the Salmonella mutation assay and the mammalian cell SCG COMET assay. The relative genotoxic risk for specific DBPs or DBP samples will be determined.
The results from this project will establish the relative toxic potencies among DBPs and their rank order within bacterial and mammalian cell assays. A relative level of genotoxic risk will be calculated for each DBP mixture as compared to the individual standard compounds used in the calibration study. Of importance is the comparison of the genotoxic responses of the S. typhimurium and CHL mammalian assays to the standard compounds. The former provides a comparative link to the literature and the latter provide an endpoint in a mammalian system that may be relevant to the human condition.