Evaluation of Estrogenic Effects of PFAS in Rats in the Rodent Uterotrophic Assay
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Per and polyfluoroalkyl substances (PFAS) are a large class of fluorinated organic chemicals of interest to regulatory agencies due to their prevalence and persistence in the environment. Multiple PFAS have been identified as endocrine disrupting chemicals due to estrogen receptor activation, impacts on puberty timing, impacts on hormonally sensitive endpoints in fish, etc. This study screened multiple PFAS in the immature rat uterotrophic assay to determine potential estrogenic effects of PFAS on the uterus, many of which had EDC activity in separate in vitro or fish screening assays. Briefly, pre-pubertal Sprague Dawley rats were ovariectomiectomized on PND 21. After a 2 week period of recovery, animals are exposed to PFAS for 5 days by oral gavage and uterine weights (with and without fluid) were taken at necropsy. In contrast to the positive control of 17β-estradiol and its typical increased uterine weight, the PFAS tested (4:2, 6:2, and 8:2FTOH; Perfluorooctanesulfonamide (PFOSA), Perfluorononanoic acid (PFNA), Perfluorohexane sulfonate (PFHxS), Nafion byproduct 2 (NBP2), 1H,1H,8H,8H-Perfluorooctane-1,8-diol (FC8-diol) and 1H,1H,10H,10H-Perfluorodecane-1,10-diol (FC10-diol) caused no significant changes in the relative uterine weight. Thus, in vitro estrogen screens and/or impacts in fish may show different responses from direct impacts on mammalian uterine weight as assessed with the uterotrophic assay. The contents of this abstract neither constitute, nor necessarily reflect, US EPA policy.