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Assessing the Toxicities of Regulated and Unregulated Disinfection By-products in Normal Human Colon Cells.
Citation:
Krishna, K. AND A. B. DEANGELO. Assessing the Toxicities of Regulated and Unregulated Disinfection By-products in Normal Human Colon Cells. Presented at Genetics Environmental Mutagenesis Society (GEMS) Fall Meeting, Chapel Hill, NC, November 08, 2011.
Impact/Purpose:
Report on the continued development of an in vitro/invivo assay for prioritizing unregulated DBPs and real world mixtures
Description:
The presence of over six hundred disinfection by-products (DBPs) and less than half of the total organic halides present in finished water has created a need for short-term in vitro assays to address toxicities that might be associated with human exposure. . We are using a normal human colon cell culture to test individual DBPs and real-world DBP mixtures for cytotoxicity and genotoxicity capability. Test System: NCM460 cells, a mixed culture of human colon mucosal cells stained positive for the epithelial cell markers and negative for endothelial cell and lymphocyte markers. The cells grew attached and in suspension and possessed the capability for differentiation, which indicated a stem cell component. The cells exhibited cytochrome P450 and GSTT1-1 activities comparable to those measured in the rat large intestine. Cytotoxicity Assay Approximately 50 regulated and unregulated DBPs from the chemical classes trihalomethanes, haloacetic acids, halonitromethanes, haloacetonitriles, haloacetamides, N-nitrosamines were tested for cytotoxicity in the growth inhibition assay (GIA). General findings: For any halogenated DBP class, iodinated species and monohalogenated DBPs were the most potent. The regulated trihalomethanes and haloacetic acids, (~70% of DBPs in chlorinated water) were less cytotoxic than the corresponding nitrogen containing DBPs, which occur at higher levels in chloraminated waters. The N-nitrosamines displayed a relatively low order of cytotoxicity. Statistically significant concordances were obtained when potencies (IC50) were ,. compared to those observed in cytotoxicity assays for mouse embryo, mammalian stem cell, and Chinese hamster ovary cell cultures. (This is an abstract of a proposed presentation and does not necessarily reflect the opinion of the US EPA.)