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Use of Normal Human Colon Cells to Assess Toxicities of Unregulated Disinfection By-products and Mixtures
Citation:
DEANGELO, A. B., B. Lyon, J. E. SIMMONS, AND H. S. WEINBERG. Use of Normal Human Colon Cells to Assess Toxicities of Unregulated Disinfection By-products and Mixtures. Presented at Associaiton for Environmental Health and Sciences Foundation, San Diego, CA, March 14 - 17, 2011.
Impact/Purpose:
Report on the continued development of an in vitro/in vivo assay for prioritizing unregulated DBPs and real world mixtures
Description:
The discovery of chlorination and chloramination by-products other than the regulated trihalomethanes and haloacetic acids has created a need for short-term in vitro assays to address toxicities that might be associated with human exposure. Approximately 600 disinfection by-products (DBPs) have been identified and these represent less than half of the total number present in finished water. We are using a mixed culture of human colon cells to test individual DBPs and real-world DBP mixtures for cytotoxicity and transformation capability. This is relevant since epidemiological studies have linked the consumption of disinfected surface waters to an increased risk of colorectal cancer. Cytotoxicity Assay: Approximately 50 regulated and unregulated DBPs have been tested for cytotoxicity (growth inhibition assay). Statistically significant concordances were obtained when the measured potencies (IC50) were compared to those observed in cytotoxicity assays developed for mouse embryo, mammalian stem cell, and Chinese hamster ovary cell cultures. Studies to determine the comparative toxicity of DBPs generated by drinking water treatments involving UV irradiation in combination with chlorination and chloramination are ongoing. Concentrates of natural organic matter from surface water are being prepared by reverse osmosis. The concentrates will be treated with UV and equivalent chlorine/cbloremlne doses, and the DBP profiles and concentrations will be determined. Transformation Assay: Growth of cells in soft agar is a feature of malignant transformation. Bromochloroacetic acid a rat colon carcinogen, dichloroacetic acid a rodent liver carcinogen, dibromonitromethane and tribromonitromethane were shown to induce cell growth in soft agar. Immunocytochemical and genomic analysis demonstrated up-regulation of the Wnt signaling pathway which is activated in >95% of human colon cancers. Validation of the assay for use on DBP mixtures is continuing, and the results will be presented. (This is the abstract of a proposed presentation and does not necessarily reflect the opinion of the US EPA.)