title: Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats.
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.
authors: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, 100 Oakdale Campus, #221 IREH, Iowa City, IA 52242, USA.
authors: Wei
authors: W
authors: Xie
authors: Qian
authors: Q
authors: Wu
authors: Izabela
authors: I
authors: Kania-Korwel
authors: Job C
authors: JC
authors: Tharappel
authors: Sanjay
authors: S
authors: Telu
authors: Mitchell C
authors: MC
authors: Coleman
authors: Howard P
authors: HP
authors: Glauert
authors: Kurunthachalam
authors: K
authors: Kannan
authors: S V S
authors: SV
authors: Mariappan
authors: Douglas R
authors: DR
authors: Spitz
authors: Jamie
authors: J
authors: Weydert
authors: Hans-Joachim
authors: HJ
authors: Lehmler
mesh_terms: D042962:Acyl-CoA Oxidase; D017738:Alkanesulfonic Acids / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000097:blood; D004785:Environmental Pollutants / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D058607:Fibric Acids; D005466:Fluorocarbons / Q000737:chemistry / Q000378:metabolism*; D006845:Hydrocarbons, Fluorinated / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000097:blood / Q000737:chemistry / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism*; D018675:Toxicity Tests; D014599:Uterus / Q000378:metabolism
chemical_list: C435127:2-(N-ethylperfluorooctanesulfonamido)ethyl alcohol; D017738:Alkanesulfonic Acids; D015415:Biomarkers; D004785:Environmental Pollutants; D058607:Fibric Acids; D005466:Fluorocarbons; D006845:Hydrocarbons, Fluorinated; D013449:Sulfonamides; D002995:Clofibric Acid; C076994:perfluorooctane sulfonic acid; D010088:Oxidoreductases; D013482:Superoxide Dismutase; C107176:peroxisomal acyl-CoA oxidase; D042962:Acyl-CoA Oxidase; C019304:ciprofibrate