Hepatotoxicity of the drinking water disinfection by-product, dichloroacetic acid, in the medaka small fish model

Toxicology Letters
J McHugh LawA B DeAngelo

Abstract

Recent studies have shown that dichloroacetic acid (DCA), a by-product of chlorination of public water supplies, is carcinogenic to both rats and mice. However, conflicting data have left the mechanism of DCA carcinogenicity, vital to assessment of human health risk, unclear. Elucidation of this mechanism in another animal model at a different phyletic level than rodents would advance the risk assessment process for government agencies concerned with regulation and provision of safe drinking water. The Japanese medaka (Oryzias latipes), a well characterized small fish model, is being used increasingly for carcinogenicity testing because of its low cost, ease of maintenance and carcinogen sensitivity. In this study, 6-week-old medaka were exposed to diethylnitrosamine (DEN, a known initiator), followed by continuous exposure to 0.5 or 2.0 g/l DCA in the ambient water, over a 4 week period. At both exposure concentrations, changes in the liver included marked hepatocellular cytoplasmic vacuolation, cytomegaly, karyomegaly, nuclear atypia and multifocal areas of hepatocellular necrosis and loss as early as week two of DCA exposure. The majority of the hepatocellular cytoplasmic vacuoles were shown by periodic acid Schiff (PAS) sta...Continue Reading

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References

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Citations

Mar 20, 2003·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·David R GeterWilliam E Hawkins
Nov 15, 2006·Journal of Clinical Pharmacology·Minghong JiaPeter W Stacpoole

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