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 ∼ 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 *Corresponding author: Hans-Joachim Lehmler, 100 Oakdale Campus, #221 IREH, Iowa City, IA, Phone: +1-319-335-4211, Fax: +1-319-335-4290, hans-joachim-lehmler@uiowa.edu. Conflict of interest:The authors declare that they have no conflict of interest. NIH Public AccessAuthor Manuscript Arch Toxicol. Author manuscript; available in PMC 2010 October 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 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.

Perfluorooctane sulfonate: A review of human exposure, biomonitoring and the environmental forensics utility of its chirality and isomer distribution

“…Some PFOS-precursors like N-Et-FOSA and N-Et-FOSE, have shown low conversion factors b1% in rats and trout (Xu et al, 2004;Tomy et al, 2004) or have not yet been studied. However, in 2003, Seacat et al reported a conversion factor to PFOS of up to 20% in a study where rats were exposed long term to N-Et-FOSE; an observation confirmed subsequently by Xie et al (2009). Although the reported levels of PFOS-precursors are generally lower and their physicochemical properties differ from those of PFOS, a variety of them have been detected in water (Ahrens et al, 2009), in indoor and outdoor air (Shoeib et al, 2005;Jahnke et al, 2007), in packaged food (Tittlemier et al, 2006), and in live organisms (from mussels to bald eagles) and waterbird eggs Wang et al, 2008).…”

Effects of exposure to BDE-99 on oxidative status of liver and kidney in adult rats

“…A decrease in SOD and CAT hepatic activities was reported by Banudevi et al (2006) in a study with male rats exposed to PCBs. Notwithstanding, in female rats treated with perfluorooctane sulfonate (PFOS), a higher activity was observed in hepatic SOD, whereas CAT activity remained unchanged (Xie et al, 2009). In the present study, alterations in SOD and CAT activities were observed in agreement with the previously mentioned studies.…”

Children's exposure to perfluoroalkyl acids – a modelling approach

“…An accurate assessment of the indirect exposure to PFCAs and PFSAs is currently unfeasible due to largely unknown values for the absorption efficiencies and PK parameters of most PFCA and PFSA precursors. 8,46 Estimations for biotransformation factors of PFAA precursors and absorption efficiencies are usually determined in rodent experiments, [47][48][49] which can hamper extrapolation to human metabolism. 7,48,50 Trudel et al (2008) proposed absorption efficiencies for PFOA and PFOS in humans being 0.66, 0.8 and 0.91, which were estimated from a study in rodents.…”