Evaluation of hepatic and thyroid responses in male Sprague Dawley rats for up to eighty-four days following seven days of dietary exposure to potassium perfluorooctanesulfonate

Clifford R. Elcombe, Barbara M. Elcombe, John R. Foster, Shu-Ching Chang, David J. Ehresman, Patricia E. Noker, John L. Butenhoff

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)


    In a prior 28-day dietary study in rats with 20 and 100 ppm K+PFOS, activation of PPAR alpha and CAR/PXR were concluded to be etiological factors in K+PFOS-induced hepatomegaly and hepatic tumorigenesis. The objective of this study was to evaluate persistence/resolution of K+PFOS-induced, liver-related effects in male Sprague Dawley rats following a 7-day dietary exposure to K+PFOS at 20 or 100 ppm. Groups of 10 rats per treatment were observed on recovery Day(s) 1, 28, 56, and 84 following treatment. Changes consistent with hepatic PPAR alpha and CAR/PXR activation noted on recovery Day 1 included: increased liver weight; decreased plasma cholesterol, alanine aminotransferase, and triglycerides; decreased liver DNA concentration and increased hepatocellular cytosolic CYP450 concentration; increased liver activity of acyl CoA oxidase, CYP4A, CYP2B. and CYP3A; increased liver proliferative index and decreased liver apoptotic index; decreased hepatocellular glycogen-induced vacuoles; increased centrilobular hepatocellular hypertrophy. Most effects resolved to control levels during recovery. Effects on plasma cholesterol, hepatocellular cytosolic CYP450 concentrations, liver apoptotic index, CYP3A, and centrilobular hepatocellular hypertrophy persisted through the end of the recovery period. Thyroid parameters (histology, apoptosis, and proliferation) were unaffected at all time points. Mean serum PFOS concentrations on recovery Day 1 were 39 and 140 mu g/mL (20 ppm and 100 ppm K+PFOS, respectively), decreasing to 4 and 26 mu g/mL by recovery Day 84. Thus, hepatic effects in male rats resulting from K+PFOS-induced activation of PPAR alpha and CAR/PXR resolved slowly or were still present after 84-days following a 7-day dietary treatment, consistent with the slow elimination rate of PFOS. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)30-40
    Number of pages11
    Issue number1-3
    Publication statusPublished - 11 Mar 2012

    Cite this