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Toxicol Sci


Title:Perfluorohexane Sulfonate (PFHxS) and a Mixture of Endocrine Disrupters Reduce Thyroxine Levels and Cause Antiandrogenic Effects in Rats
Author(s):Ramhoj L; Hass U; Boberg J; Scholze M; Christiansen S; Nielsen F; Axelstad M;
Address:"Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, DK-2800 Lyngby, Denmark. Institute of Environment, Health and Societies, Brunel University London, Uxbridge UB8 3PH, UK. Environmental Medicine, Institute of Public Health, University of Southern Denmark, DK-5000 Odense, Denmark"
Journal Title:Toxicol Sci
Year:2018
Volume:163
Issue:2
Page Number:579 - 591
DOI: 10.1093/toxsci/kfy055
ISSN/ISBN:1096-0929 (Electronic) 1096-0929 (Linking)
Abstract:"The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk. To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of 12 environmentally relevant endocrine disrupting chemicals (EDmix). Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS, and two doses of PFHxS + EDmix (n = 5-7). Study 2 included control, 0.05, 5, or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5, or 25 mg PFHxS/kg plus EDmix (n = 13-20). PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused antiandrogenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate, and vesicular seminalis. PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account"
Keywords:"Androgen Antagonists/*toxicity Animals Animals, Newborn Dose-Response Relationship, Drug Endocrine Disruptors/*toxicity Female Fluorocarbons Male Pregnancy Prenatal Exposure Delayed Effects/blood/*chemically induced/physiopathology Rats Reproduction/drug;"
Notes:"MedlineRamhoj, Louise Hass, Ulla Boberg, Julie Scholze, Martin Christiansen, Sofie Nielsen, Flemming Axelstad, Marta eng Research Support, Non-U.S. Gov't 2018/03/09 Toxicol Sci. 2018 Jun 1; 163(2):579-591. doi: 10.1093/toxsci/kfy055"

 
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