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Toxicologic Pathology, Vol. 29, No. 6, 662-669 (2001)
DOI: 10.1080/019262301753385997

Chronic Toxicity of Bromodichloromethane to the Japanese Medaka (Oryzias latipes)

Margaret W. Toussaint

GEO-CENTERS, Fort Detrick, Maryland, Margaret.Toussaint{at}amedd.arm y.mil

Alan B. Rosencrance

U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland

Linda M. Brennan

GEO-CENTERS, Fort Detrick, Maryland

William E. Dennis

GEO-CENTERS, Fort Detrick, Maryland

Joseph R. Beaman

GEO-CENTERS, Fort Detrick, Maryland

Marilyn J. Wolfe

Experimental Pathology Laboratory, Herndon, Virginia

Florence J. Hoffmann

U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland

Henry S. Gardner, JR

U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland

Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured bromodichloromethan e (BDCM) concentrations of 0.018, 0.143, or 1.424 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic BDCM concentration. BDCM was not hepatocarcinogeni c to medaka at the concentrations tested. Chronic toxicity was evidenced at 6 and 9 months by statistically significant ({alpha} =0.05) levels of gallbladder lesions and bile duct abnormalities in medaka treated with 1.424 mg/L BDCM. Hepatocellular proliferation was assessed after 1, 4, and 20 days of BDCM exposure. Treatment-related increases or decreases in cellular proliferation were not observed at any time point. Hematocrit, leukocrit, cell viability, and cell counts of treated fish after 9 months of BDCM exposure were not significantly different from control fish. Intrahepatic concentrations were evaluated by gas chromatography after 9 months of BDCM exposure. Fish livers from all three BDCM treatments had detectable amounts of BDCM, with median intrahepatic concentrations of 1.02, 2.89, and 21.25 mg BDCM/kg fish liver in the low, middle, and high concentrations, respectively. Medaka chronic toxicity effects of statistically significant gallbladder and bile duct abnormalities occurred at 1.424 mg/L BDCM, well above median drinking water levels.

Key Words: Bromodichloromethane • fish • carcinogenicity • cell proliferation • 5-bromo-2'-deoxyuridine • medaka • aquatic toxicology • Oryzias latipes.


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