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Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats
Journal article   Open access   Peer reviewed

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

Wei Xie, Qian Wu, Izabela Kania-Korwel, Job C Tharappel, Sanjay Telu, Mitchell C Coleman, Howard P Glauert, Kurunthachalam Kannan, S V S Mariappan, Douglas R Spitz, …
Archives of toxicology, Vol.83(10), pp.909-924
10/2009
DOI: 10.1007/s00204-009-0450-y
PMCID: PMC2755535
PMID: 19544052
url
http://doi.org/10.1007/s00204-009-0450-yView
Open Access

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 approximately 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.
Fluorocarbons - chemistry Uterus - metabolism Fluorocarbons - metabolism Hydrocarbons, Fluorinated - blood Environmental Pollutants - blood Sulfonamides - blood Clofibric Acid - blood Clofibric Acid - analogs & derivatives Female Fibric Acids Environmental Pollutants - toxicity Alkanesulfonic Acids - metabolism Superoxide Dismutase - metabolism Biomarkers - metabolism Oxidoreductases - metabolism Sulfonamides - chemistry Liver - metabolism Rats Hydrocarbons, Fluorinated - chemistry Rats, Sprague-Dawley Superoxide Dismutase - drug effects Hydrocarbons, Fluorinated - toxicity Animals Environmental Pollutants - chemistry Sulfonamides - toxicity Toxicity Tests Alkanesulfonic Acids - chemistry

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