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ASSESSING THE EFFECTS OF DICHLOROACETIC ACID (DCA) USING A MULTI-ENDPOINT MEDAKA ASSAY
Citation:
Johnson, R. D., P. K. Schmieder, R. N. Winn, D B. Lothenbach, K. M. Flynn, D E. Hammermeister, R. Whitman, R. Whitman, A Deangelo, AND D C. Wolf. ASSESSING THE EFFECTS OF DICHLOROACETIC ACID (DCA) USING A MULTI-ENDPOINT MEDAKA ASSAY. Presented at 2002 SETAC Annual Meeting, Salt Lake City, UT, November 16-20, 2002.
Description:
In regulating the safety of water, EPA makes decisions on what chemical contaminants to regulate and at what levels. To make these decisions, the EPA needs hazard identification and dose-response information. Current rodent methods for generating required information have limitations for determining the risks of long-term exposure to low chemical concentrations found in drinking-, ground-, or surface-water. Examples include: a) difficulty in delivering an effective toxicant dose through drinking water, b) up to two year exposure times are often required for cancer endpoints; c) large sample sizes for assessing low frequency events (e.g., cancer or developmental anomalies) are costly; and d) assessing the effects of chemical mixtures sometimes requires the costly and difficult preparation of water concentrates. We are developing a multi-endpoint medaka assay to: a) assess reproductive, developmental and carcinogenic effects of chemicals in water; and b) to evaluate the comparability of risk assessment endpoints across rodent and fish species on a dose-dependent basis. The results of a nine-month medaka exposure to dichloroacetic acid, at concentrations up to 10 times lower than used in rodent assays, include dose- and time-dependent increases in mutation frequencies (recorded in transgenic medaka), parallel changes in medaka and rodents with respect to hepatocyte glycogen and liver pathology. Comparison of DCA effects in rodents and medaka support the assertion that data from medaka assays are useful for assessing the effects of long-term exposures to chemicals in water at low concentrations.