Tissue distribution, excretion, and urinary metabolites of dichloroacetic acid in the male Fischer 344 rat
Lin, ELC; Mattox, JK; Daniel, FB
HERO ID
706762
Reference Type
Journal Article
Year
1993
Language
English
PMID
| HERO ID | 706762 |
|---|---|
| In Press | No |
| Year | 1993 |
| Title | Tissue distribution, excretion, and urinary metabolites of dichloroacetic acid in the male Fischer 344 rat |
| Authors | Lin, ELC; Mattox, JK; Daniel, FB |
| Journal | Journal of Toxicology and Environmental Health |
| Volume | 38 |
| Issue | 1 |
| Page Numbers | 19-32 |
| Abstract | 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. |
| Doi | 10.1080/15287399309531697 |
| Pmid | 8421320 |
| Wosid | WOS:A1993KH54200002 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Is Peer Review | Yes |