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MECHANISTIC INFORMATION ON DISINFECTION BY-PRODUCTS FOR RISK ASSESSMENT
Citation:
Demarini, D M. MECHANISTIC INFORMATION ON DISINFECTION BY-PRODUCTS FOR RISK ASSESSMENT. Presented at Genotoxicity and Immunotoxicity: Health Effects in Aquatic Systems, Koblenz, Germany, April 22-24/2004.
Description:
Colon cancer is the second most common cancer in people from developed countries, and populations exposed t o 50?g/L or more of trihalomethanes for at 1east 35 years have been estimated to be 1.5 times more likely to develop colon cancer. Trihalomethanes are one of the classes of carcinogenic disinfection by-products in drinking water that are regulated currently in the U.S. Alternative disinfection methods, such as chloramination and ozonation rather than chlorination, are currently being encouraged in the U.S. to reduce the levels of trihalomethanes. However, a recent survey in the U.S. has shown that these alternative disinfectants resulted in increased levels of other, potentially carcinogenic disinfection by-products, such as brominated halonitromethanes, MX and brominated MXs, and iodohalomethanes. This was especially the case if the source waters contained high levels of bromine. Thus, further assessment of these alternative disinfection methods is needed to see if the drinking water produced by such methods is necessarily less mutagenic than that produced by chlorine alone. Considering evidence in human and rodents, it is possible that the human epidemiology linking colorectal cancer and bladder cancer to consumption of chlorinated drinking water may, in fact, reflect dermal (and inhalation) rather than oral exposure. Dermal adsorption permits disinfection by-products to enter directly into the blood stream, bypass the liver, and be transported without significant metabolism to the colon and bladder. The relative proportion of GSTT1-1 activity, which activates brominated trihalomethanes, to the activities of P450s is greater in the colon than in other potential target tissues, such as the liver. Thus, the disinfection by-products obtained through dermal exposure may be more likely to be activated to mutagens by GSTT1-1 rather than inactivated by P450 activities in the colon and bladder, resulting in the observed increased cancer risk for these organs. Current risk assessments do not include the newly discovered halonitromethanes, which may be present in water disinfected with chloramine at levels similar to those of the halomethanes in water disinfected by chlorine. The halonitromethanes are 10-100 times more cytotoxic and mutagenic than the halomethanes, although they are not activated by GSTT1-1. Mutation spectra studies of drinking water extracts and disinfection byproducts have been performed in Salmonella. However, no molecular epidemiology studies of drinking water have been performed to see if there are mutation patterns in tumors that would reflect exposure to disinfection by-products. Further studies need to be conducted in rodents and humans to clarify whether dermal and inhalation exposure to disinfection by-products may result in a greater risk for colorectal and bladder cancer than oral exposures. [Abstract does not necessarily reflect the policy of the US EPA.]