Archives of Toxicology

, Volume 83, Issue 10, pp 909–924

Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats

Authors

  • Wei Xie
    • Department of Occupational and Environmental Health, College of Public HealthThe University of Iowa
  • Qian Wu
    • Wadsworth Center, New York State Department of Health and Department of Environmental Health SciencesState University of New York
  • Izabela Kania-Korwel
    • Department of Occupational and Environmental Health, College of Public HealthThe University of Iowa
  • Job C. Tharappel
    • Graduate Center for Nutritional SciencesUniversity of Kentucky
  • Sanjay Telu
    • Department of Occupational and Environmental Health, College of Public HealthThe University of Iowa
  • Mitchell C. Coleman
    • Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer CenterThe University of Iowa
  • Howard P. Glauert
    • Graduate Center for Nutritional SciencesUniversity of Kentucky
    • Graduate Center for ToxicologyUniversity of Kentucky
  • Kurunthachalam Kannan
    • Wadsworth Center, New York State Department of Health and Department of Environmental Health SciencesState University of New York
  • S. V. S.  Mariappan
    • Department of Chemistry, College of Liberal Arts and SciencesThe University of Iowa
  • Douglas R. Spitz
    • Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer CenterThe University of Iowa
  • Jamie Weydert
    • Department of Pathology, Carver College of MedicineThe University of Iowa
    • Department of Occupational and Environmental Health, College of Public HealthThe University of Iowa
Toxicokinetics and Metabolism

DOI: 10.1007/s00204-009-0450-y

Cite this article as:
Xie, W., Wu, Q., Kania-Korwel, I. et al. Arch Toxicol (2009) 83: 909. doi:10.1007/s00204-009-0450-y

Abstract

Perfluorooctanesulfonamides, such as N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE), are large scale industrial chemicals but their disposition and toxicity are poorly understood despite significant human exposure. The hypothesis that subacute exposure to N-EtFOSE, a weak peroxisome proliferator, causes a redox imbalance in vivo was tested using the known peroxisome proliferator, ciprofibrate, as a positive control. Female Sprague–Dawley rats were treated orally with N-EtFOSE, ciprofibrate or corn oil (vehicle) for 21 days, and levels of N-EtFOSE and its metabolites as well as markers of peroxisome proliferation and oxidative stress were assessed in serum, liver and/or uterus. The N-EtFOSE metabolite profile in liver and serum was in good agreement with reported in vitro biotransformation pathways in rats and the metabolite levels decreasing in the order perfluorooctanesulfonate ≫ perfluorooctanesulfonamide ~ N-ethyl perfluorooctanesulfonamidoacetate ≫ perfluorooctanesulfonamidoethanol ~ N-EtFOSE. Although N-EtFOSE treatment significantly decreased the growth rate, increased relative liver weight and activity of superoxide dismutases (SOD) in liver and uterus (total SOD, CuZnSOD and MnSOD), a metabolic study revealed no differences in the metabolome in serum from N-EtFOSE-treated and control animals. Ciprofibrate treatment increased liver weight and peroxisomal acyl Co-A oxidase activity in the liver and altered antioxidant enzyme activities in the uterus and liver. According to NMR metabolomic studies, ciprofibrate treated animals had altered serum lipid profiles compared to N-EtFOSE-treated and control animals, whereas putative markers of peroxisome proliferation in serum were not affected. Overall, this study demonstrates the biotransformation of N-EtFOSE to PFOS in rats that is accompanied by N-EtFOSE-induced alterations in antioxidant enzyme activity.

Keywords

MetabolomicsPerfluorooctanesulfonamidesPerfluorooctanesulfonatePeroxisomal acyl Co-A oxidaseSuperoxide dismutase

Supplementary material

204_2009_450_MOESM1_ESM.docx (269 kb)
Supplementary material 1 (DOCX 268 kb)

Copyright information

© Springer-Verlag 2009