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MUTAGENICITY IN SALMONELLA OF HALONITROMETHANES: A RECENTLY RECOGNIZED CLASS OF DISINFECTION BY-PRODUCTS IN DRINKING WATER
Citation:
Kundu, B., S. D. Richardson, P. D. Swartz, P. P. Mathews, A. M. Richard, AND D M. DeMarini. MUTAGENICITY IN SALMONELLA OF HALONITROMETHANES: A RECENTLY RECOGNIZED CLASS OF DISINFECTION BY-PRODUCTS IN DRINKING WATER. MUTATION RESEARCH 562(1-2):39-65, (2004).
Impact/Purpose:
To evaluate the mutagenicity of 9 halonitromethanes
Description:
Halonitromethanes (HNMs) are a recently identified class of disinfection by-products in drinking water. They include chloronitromethane (CHN), dichloronitromethane (DCNM), trichloronitromethane (TCNM), bromonitromethane (BNM), dibromonitromethane (DBNM), tribromonitromethane (TBNM), bromochloronitromethane (BCNM),dibromochloronitromethane (DBCNM), and bromodichloronitromethane (BDCNM). Previous studies of TCNM, DCNM, CNM, and TBNM found that all 4 were mutagenic in bacteria, and a recent study showed that all 9 induced DNA damage in CHO cells. Here, all 9 HNMs were evaluated in the Salmonella plate-incorporation assay +/- S9 using strains TA98, TA100, TA104, TPT100, and RSJ100, which expresses rat GSTT1-1. All but DBCNM were mutagenic in TA 100, most with and without S9. Approximately half were mutagenic in TA98, only a few were positive in TA104, and all but BNM, which was negative, were weakly mutagenic in RSJ100. Thus, the HNMs induced primarily base-substitutions presumptively at GC sites, and, unlike the halomethanes, the HNMs were not activated to mutagens by GSTT1-1. The rank order of the mutagenic potencies in TA100 +S9 was (BCNM > DBNM) > (TBNM ? CNM > BNM ? BDCNM ? DCNM) > (TCNM > DBCNM), with mean rev/?mole values of 1622, 571, and <50 in the 3 major activity groupings. The dependence of TCNM and TBNM mutagenicity on S9 is likely due to required dehalogenation, whereas further reaction of the dihalo and monohalo HNMs with endogenous GSH, in this case not mediated by GSTT1-1, has been proposed as a likely mechanism for formation of ultimate mutagenic products. Because the HNMs are mutagenic in Salmonella (present study) and potent clastogens in mammalian cells (Environ. Sci. Technol., in press, 2004), their presence in drinking water warrants further research on their potential health effects.