Genotoxic and Carcinogenic Properties of Chlorinated Furanones: Important By-Products of Water Chlorination

摘要

The widespread presence of genotoxins in drinking water can be directly linked to the chlorination stage of drinking water treatment. Recent studies in Finland, the United States and Great Britain have shown that a single compound, 3-chloro-4-(dichlo-romethyl)-5-hydroxy-2(5H)-furanone (MX), is responsible for a substantial fraction of the mutagenicity of chlorinated drinking water. Several other chlorinated furanones that appear to contribute to the mutagenicity have also been identified. The toxicological data available on MX has been limited to its identification as a potent direct-acting mutagen in Salmonella. The results of additional studies aimed at evaluating the potential health effects of MX can be summarized as follows: MX induces DNA strand breaks and chromosomal aberrations in cultured mammalian cells, and forms a single major DNA adduct in both bacterial and mammalian cells; the mutagenic and clastogenic effects are substantially reduced by liver S-9 fraction, which can be partly attributed to conjugation with glutathione via glutathione-S-transferase; MX is inactive as a clastogen in bone marrow and marginally active in gastrointestinal tissue of mice when given by oral gavage; at least 40% of orally administered MX is absorbed, and greater than 80% is excreted via feces and urine within 48 hr; MX appears to induce skin tumors in mice when given orally but not topically. A chronic bioassay in mice is planned to help define the carcinogenic risk associated with exposure to MX in drinking water.