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HEPATOTOXIC EVALUATION OF THE BINARY INTERACTIONS OF BROMODICHLOROMETHANE WITH CHLOROFORM, CHLORODIBROMOMETHANE AND BROMOFORM
Citation:
Sey, Y M., C. Gennings, A McDonald, L K. Teuschler, AND J E. Simmons. HEPATOTOXIC EVALUATION OF THE BINARY INTERACTIONS OF BROMODICHLOROMETHANE WITH CHLOROFORM, CHLORODIBROMOMETHANE AND BROMOFORM. Presented at SOT, San Francisco, CA, March 25 - 29, 2001.
Description:
HEPATOTOXIC EVALUATION OF THE BINARY INTERACTIONS OF BROMODICHLOROMETHANE (BDCM) WITH CHLOROFORM (CHC13), CHLORODIBROMOMETHANE (CDBM) AND BROMOFORM (CHBr3). Y M Se'', C Gennings2, A McDonald', L K Teuschler3, A Hamm2and J E Simmons .'NHEERL, ORD, U.S. EPA, RTP, NC; 2MCV, VCU, Richmond, VA; 3NCEA, ORD, U.S. EPA, Cincinnati, OH.
Trihalomethanes (THMs) result from chlorination or chloramination of water. Acute and chronic exposures to individual THMs have been associated with target organ toxicity and tumorigenesis. Since humans are exposed to multiple rather than single chemicals, information on mixtures of THMs is needed. Three experiments were conducted to meet the objective of examining the binary interactions of BDCM, the most prevalent brominated THM, with the other 3 THMs. Each experiment consisted of: an aqueous control group; BDCM alone at 0.1, 1.0 or 3.0 mmol/kg/day; either CDBM alone, CHC13 alone or CHBr3 alone at 0.1, 1.0 or 3.0 mmol/kg/day; 3 mixture groups at a 1:1 mixing ratio and total dosages of 0.1, 1.0 or 3.0 mmol/kg/day; and, 2 mixture groups at total dosages of 1.0 or 3.0 mmol/kg/day and varied mixing ratios (2.7:1 CHCl3:BDCM; 2.4:1 BDCM:CDBM; 24:1 BDCM:CHBr3) based on the average seasonal proportions of the THMs at 35 water treatment facilities (Krasner et al., 1989). Female CD-1 mice were gavaged daily for 14 days. Hepatotoxicity was assessed by serum SDH. Data were analyzed with a threshold dose-additivity model (Gennings et al., 1998). For BDCM:CHC13, the closeness of the predicted and observed values indicated no deviation from dose additivity. For BDCM:CHBr3, significant deviation (antagonism) from dose additivity was detected only at 3.0 mmol/kg/day of the 1:1 mixture. For BDCM:CDBM, borderline statistical significance was observed (p=0.056); with a possible trend of nonadditivity (antagonism) at the 1:1 mixing ratio. This and the small sample size due to mortality indicate further evaluation of BDCM:CDBM is needed. In summary, the present data indicate that the binary interactions among the THMs at these mixture dosages and mixing ratios are either additive or antagonistic but not synergistic. (This abstract does not reflect EPA policy.)