Repeated-Dose Gavage Studies on Polychlorotrifluoroethylene Acids

Abstract

C8 polychlorotrifluoroethylene (pCTFE) oligomers accumulate preferentially in the liver during long-term oral exposure and appear to be more hepatotoxic than C6 oligomers. A repeated-dose gavage study was initiated to determine the relative contributions of the corresponding C6 (trimer) and C8 (tetramer) acid metabolites to the toxicity of pCTFE in the male Fischer 344 rat. Test animals were dosed once per week for various time periods up to one year. A depression (p < 0.05) in mean body weight occurred in the highest dose tetramer acid (2.16 mg/kg) group. An increase in hepatic peroxisomal β-oxidation activity was found in the 2.16 mg pCTFE tetramer acid/kg dose group at the 3-, 6-, and 9-month sacrifice periods. An increase in relative liver weight was seen at all sacrifice periods in this dose group. Hepatocellular cytomegaly was a common finding in the higher dose tetramer acid groups but not in the trimer-treated rat groups.

Get full access to this article

View all access options for this article.

References

Barcikowski, R.S. , ed. (1983). Computer Packages and Research Design, Vol. 1: BMDP, University Press of America , Lanham, Maryland.

Dixon, W.J. (1985). BMDP Statistical Software. University of California Press, Berkeley, California .

George, M.E. and Andersen, M.E. (1986). Toxic effects of nonadecafluoro-n-decanoic acid in rats. Toxicol. Appl. Pharmacol. 85:169-180.

Kinkead, E.R. , Gaworski, C.L. , Horton, J.R. and Boosinger, T.R. (1987). Chlorotrifluoroethylene Oligomer: Evaluation of Acute, Delayed Neurotoxicity in Hens, and Study of Absorption and Metabolism in Fats following Oral, Dermal, and Inhalation Exposure. AAMRL-TR-87-044 (AD 187611), Harry G. Armstrong Aerospace Medical Research Laboratory , Wright-Patterson Air Force Base, Ohio.

Kinkead, E.R. , Kimmel, E.C. , Wall, H.G. , Conolly, R.B. , Kutzman, R.S. , Whitmire, R.E. and Mattie, D.R. (1990a). Subchronic inhalation studies on polychlorotrifluoroethylene (3.1 Oil). Inhalation Toxicology 2:431-449.

Kinkead, E.R. , Culpepper, B.T. , Henry, S.S. , Szotak, P.S. , Flemming, C.D. , Kutzman, R.S. , Bruner, R.H. , Wyman, J.F. and Mattie, D.R. (1990b). The determination of the repeated oral toxicity of halocarbon oil, series 27-s. Toxicol. Indust. Health 6:17-32.

Olson, C.T. and Andersen, M.E. (1983). The acute toxicity of perfluorooctanoic and perfluorodecanoic acids in male rats and effects on tissue fatty acids. Toxicol. Appl. Pharmacol. 70:362-372.

Sas Institute, Inc. (1985). SAS User's Guide: Statistics, Version 5 Edition. SAS Institute, Inc., Cary, North Carolina.

Van Rafelghem, M.J. , Mattie, D.R. , Bruner, R.H. and Andersen. M.E. (1987). Pathological and hepatic ultrastructural effects of a single dose of perfluoron-decanoic acid in the rat, hamster, mouse, and guinea pig. Fund. Appl. Toxicol. 9:522-540.

10.

Vinegar, A. , Seckel, C.S. , Pollard, D.L. , Kinkead, E.R. , Conolly, R.B. , and Andersen, M.E. (1991). Physiologically based model of polychlorotrifluoroethylene oligomer pharmacokinetics in Fischer 344 rats. Fund. Appl. Toxicol. (submitted).

11.

Zar, J.R. (1974). Biostatistical Analysis, pp. 105-106. Prentice Hall, Englewood Cliffs, New Jersey.