Superfund Research Program
Studies Examine Cardiac Teratogenicity of a Common Drinking Water Contaminant
Trichloroethylene (TCE) is the country's most frequently detected contaminant in groundwater, where the compound poses some particular problems. Once TCE makes its way into subterranean conduits of water, it can take years to degrade. Because many private and municipal water supplies tap these underground water sources for human consumption, significant exposures often occur. Sometimes these water supplies even show average TCE levels above current U.S. drinking water quality standards. TCE's persistent presence in groundwater is disconcerting as the compound's toxicity becomes better understood and people continue to rely on groundwater as a source of drinking water.
Several epidemiological studies have found an association between TCE and an increased incidence of congenital cardiac disease in the children of mothers exposed to contaminated water during pregnancy. Laboratory studies in animals have further implicated TCE, and other halogenated hydrocarbon compounds, as teratogens that interfere with the normal development of the embryonic heart. In response to increasing public health concern, researchers at the University of Arizona have initiated a series of investigations to elucidate the doses of compound, as well as the cellular and molecular mechanisms, that lead to TCE-induced cardiac teratogenicity.
In a dose response study, drinking water containing levels of TCE (2.5 ppb to 1100 ppm) relevant to human exposures was administered to pregnant Sprague-Dawley rats. This specific strain of rat was used because of similar gestational stages and congenital heart malformation rates to that of humans. The findings of this experiment demonstrate significantly increased rates of congenital heart malformation in the offspring of high level TCE maternal exposure, in comparison with controls. The results also showed an apparent statistical trend in increasing dose response.
In addition, several mammalian metabolites of TCE and dichloroethylene (DCE) were tested in the pregnant rat model to assess the specific compounds responsible for TCE-induced cardiac teratogenicity. Only one TCE metabolite, trichloracetic acid (TCAA), showed any cardiac teratogenic effects. The other metabolites tested in the animal model did not show increased rates of congenital heart malformations in offspring. These results suggest that TCAA may be the TCE metabolite responsible for producing heart defects in the rat and are consistent with dosage and results found by other researchers.
Further studies of drinking water exposure are proceeding. Research is currently being carried out to elucidate the mechanisms of the effects that TCE, DCE, and TCAA produce on previously identified critical determinants in heart formation. Scientists are looking for evidence of specific perturbations in gene expression during cardiac organogenesis. These studies will lead to the identification of the cellular targets of the teratogenic compounds and to the elucidation of the processes of TCE-induced malformation that result in cardiac defects. With this information the scientists will then be able to correlate the results of the animal studies to humans.
In recent years it has become clear that some environmental chemicals can cause risks to the developing embryo and fetus. Evaluating the developmental toxicity of environmental chemicals is now a prominent public health concern. The suspected association between TCE and congenital cardiac malformations - first noted in epidemiological studies - warrants special attention because TCE is a common drinking water contaminant that is detected in water supplies throughout the U.S. and the world. These studies are significant for addressing an important public health concern and advancing our basic knowledge and understanding of the role that TCE may play in disrupting normal heart development.
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