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      Groundwater and the Environment: Applications for the Global Community 

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      CRC Press

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          Clinical pharmacology and toxicology of dichloroacetate.

          Dichloroacetate (DCA) is a xenobiotic of interest to both environmental toxicologists and clinicians. The chemical is a product of water chlorination and of the metabolism of various drugs and industrial chemicals. Its accumulation in groundwater and at certain Superfund sites is considered a potential health hazard. However, concern about DCA toxicity is predicated mainly on data obtained in inbred rodent strains administered DCA at doses thousands of times higher than those to which humans are usually exposed. In these animals, chronic administration of DCA induces hepatotoxicity and neoplasia. Ironically, the DCA doses used in animal toxicology experiments are very similar to those used clinically for the chronic or acute treatment of several acquired or hereditary metabolic or cardiovascular diseases. As a medicinal, DCA is generally well tolerated and stimulates the activity of the mitochondrial pyruvate dehydrogenase enzyme complex, resulting in increased oxidation of glucose and lactate and an amelioration of lactic acidosis. By this mechanism, the drug may also enhance cellular energy metabolism. DCA is dehalogenated in vivo to monochloroacetate and glyoxylate, from which it can be further catabolized to glycolate, glycine, oxalate, and carbon dioxide. It remains to be determined whether important differences in its metabolism and toxicology exist in humans between environmentally and clinically relevant doses. Images Figure 1 Figure 2
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            Environmental ecology of Cryptosporidium and public health implications.

            Cryptosporidium has become the most important contaminant found in drinking water and is associated with a high risk of waterborne disease particularly for the immunocompromised. There have been 12 documented waterborne outbreaks in North America since 1985; in two of these (Milwaukee and Las Vegas) mortality rates in the immunocompromised ranged from 52% to 68%. The immunofluorescence antibody assay (IFA) using epifluorescence microscopy has been used to examine the occurrence of Cryptosporidium in sewage (1 to 120 oocysts/liter), filtered secondary treated wastewater (0.01 to 0.13 oocysts/liter), surface waters (0.001 to 107 oocysts/liter), groundwater (0.004 to 0.922 oocysts/liter) and treated drinking water (0.001 to 0.72 oocysts/liter). New rules are being developed (Information Collection Rule and Enhanced Surface Water Treatment Rule) to obtain more occurrence data for drinking water systems for use with new risk assessment models. Public health officials should consider a communication program to physicians treating the immunocompromised, nursing homes, develop a plan to evaluate cases of cryptosporidiosis in the community, and contribute to the development of public policies that limit contamination of source waters, improve water treatment, and protect public health.
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              Waterborne Outbreak of Viral Gastroenteritis

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                Book Chapter
                June 21 2000
                December 16 2009
                : 163-168
                10.1201/9781420032895.bmatt1
                0368b01e-1f73-4246-bd3f-dc4ed1b69e6d
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