The disposition of dichloroacetic acid (DCA) was investigated in Fischer 344 rats over the 48 h after oral gavage of 282 mg/kg of 1- or 2-[14C]-DCA (1-DCA or 2-DCA) and 28.2 mg/kg of 2-DCA. DCA was absorbed quickly, and the major route of disposition was through exhalation of carbon dioxide and elimination in the urine. The dispositions of 1- and 2-DCA at 282 mg/kg were similar. With 2-DCA, the disposition differed with dose in that the percentage of the dose expired as carbon dioxide decreased from 34.4% (28.2 mg/kg) to 25.0% (282 mg/kg), while the percentage of the radioactivity excreted in the urine increased from 12.7 to 35.2%. This percentage increase in the urinary excretion was mostly attributable to the presence of unmetabolized DCA, which comprised more than 20% at the higher dose and less than 1% at the lower dose. The major urinary metabolites were glycolic acid, glyoxylic acid, and oxalic acid. DCA and its metabolites accumulated in the tissues and were eliminated slowly. After 48 h, 36.4%, 26.2%, and 20.8% of the dose was retained in the tissues of rats administered 28.2 and 282 mg/kg of 2-DCA and 282 mg/kg of 1-DCA, respectively. Of the organs examined, the liver (4.9-7.9% of dose) and muscle (4.5-9.9%) contained the most radioactivity, followed by skin (3.3-4.5%), blood (1.4-2.6%), and intestines (1.0-1.7%). One metabolite, glyoxylic acid, which is mutagenic, might be responsible for or contribute to the carcinogenicity of DCA.
A synchronous fluorescent spectroscopy (SFS) method was developed to measure pyrene‐type metabolites in the bile of brown bullhead (Ameiurus nebulosus) and to estimate the exposure of fish to PAHs in four Lake Erie tributaries collected in the spring and fall of 1990 and 1991. For comparison, fish biliary benzo[a]pyrene (B[a]P) metabolites were also measured by HPLC/fluorescent detection (HPLC/F). Both methods showed that concentrations of biliary PAH metabolites of fish collected in polluted rivers were significantly higher than those collected from reference rivers. Concentrations of biliary metabolites of fish caught in the Black River were five to 20 times greater than those collected in Old Woman Creek by SFS and three to five times greater by HPLC/F. Fish from the Cuyahoga River had four to 24 times more biliary PAH metabolites than fish from Old Woman Creek, measured by SFS, and five to 10 times more, measured by HPLC/F. Brown bullhead from the Tous‐saint River had fewer PAH metabolites than fish from Old Woman Creek. Correlation analyses of the two sets of data obtained by SFS and HPLC/F showed significance by both Pearson's sample correlation and Spearman's rank correlation. This study indicates that pyrene‐type metabolites determined by SFS can be used to estimate B[a]P‐type metabolites in fish bile. SFS appears to be a highly sensitive method for detecting PAH metabolites and, because of its simplicity, a cost‐efficient method for screening large numbers of samples for exposure to PAHs in fish.
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