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Toxicologic Pathology
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Histopathology of Japanese Medaka (Oryzias latipes) Chronically Exposed to a Complex Environmental Mixture

Margaret W. Toussaint

GEO-CENTERS, INC., Fort Detrick, Maryland 21702-5010

Marilyn J. Wolfe

Experimental Pathology Laboratory, Herndon, Virginia 20172

Dennis T. Burton

University of Maryland, Wye Research and Education Center, Queenstown, Maryland 21658-0169

Florence J. Hoffmann

U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702-5010

Tommy R. Shedd

U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702-5010

Henry S. Gardner, JR

U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland 21702-5010

Japanese medaka (Oryzias latipes) were used to evaluate the carcinogenicity of a complex groundwater that contained 5 U.S. Environmental Protection Agency priority pollutant heavy metals and 13 chlorinated aliphatic hydrocarbons. A test protocol that used 10 mg/L diethylnitrosamine (DEN) prior to groundwater exposure was designed to assess both initiation and promotion. The fish were exposed continuously for 9 mo with 0, 1, 5, or 25% groundwater, by volume, with either West Branch of Canal Creek water (Aberdeen Proving Ground-Edgewood Area, Aberdeen Proving Ground, MD) or dechlorinated tap water as the diluent, while concurrent controls were run in the laboratory. Incidental findings included various neoplasms in the nares, ovary, skeletal muscle, skin, swim bladder, testis, thymus, and thyroid. Factors evaluated during statistical analyses of fish neoplasm prevalence included diluent type, groundwater percentage, fish gender, and DEN initiation. Liver neoplasm prevalence was higher in DEN-initiated fish and was frequently higher in males. Concentrations of up to 25% groundwater, by volume, showed no evidence of being a complete carcinogen and showed no consistent, conclusive evidence of being a promoter.

Key Words: Carcinogenesis • fish • Japanese medaka • liver neoplasms • chemical mixture • groundwater • heavy metals • chlorinated aliphatic hydrocarbons

Toxicologic Pathology, Vol. 27, No. 6, 652-663 (1999)
DOI: 10.1177/019262339902700607


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