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Repeated-dose gavage studies on polychlorotrifluoroethylene acids
E R Kinkead1, S K Bunger, R E Wolfe
1NSI Technology Services Corporation/Mantech Environmental Technology, Inc., Dayton, Ohio 45431-0009.
Toxicology and Industrial Health
|July 1, 1991
Summary
Polychlorotrifluoroethylene (pCTFE) C8 oligomers are more hepatotoxic than C6, causing liver damage and weight loss in rats. C8 acid metabolites, not C6, were linked to these toxic effects in a long-term study.
Area of Science:
- Environmental toxicology
- Hepatotoxicity research
- Chemical safety assessment
Background:
- Polychlorotrifluoroethylene (pCTFE) oligomers are environmental contaminants.
- Previous studies suggest C8 pCTFE oligomers accumulate in the liver and exhibit higher toxicity than C6 oligomers.
Purpose of the Study:
- To investigate the specific toxicity of C6 (trimer) and C8 (tetramer) acid metabolites of pCTFE.
- To determine the dose-dependent effects and target organs of these metabolites in male Fischer 344 rats.
Main Methods:
- A repeated-dose gavage study was conducted in male Fischer 344 rats.
- Animals were administered weekly doses of C6 or C8 pCTFE acid metabolites for up to one year.
- Body weight, liver weight, hepatic peroxisomal beta-oxidation, and histopathology were assessed at various time points.
Main Results:
- The highest dose of C8 tetramer acid (2.16 mg/kg) led to a significant depression in mean body weight.
- Increased hepatic peroxisomal beta-oxidation and relative liver weight were observed in the high-dose C8 tetramer acid group.
- Hepatocellular cytomegaly was prevalent in rats exposed to higher doses of C8 tetramer acid, but not C6 trimer acid.
Conclusions:
- C8 pCTFE acid metabolites are more hepatotoxic than C6 metabolites.
- The observed liver toxicity, including cytomegaly and altered metabolic activity, is primarily attributed to C8 tetramer acid exposure.
- These findings highlight the differential toxicity of pCTFE oligomer chain lengths and their metabolites.