Citation:

Ramhoej, L., U. Haas, C. Wood, M. Gilbert, D. Usal, J. Boberg, A. Vinggaard, AND M. Axelstad. Developmental Exposure to Perfluorohexane Sulfonate (PFHxS) Induces Hypothyroxinemia in Rat Dams and Offspring: Examination of Thyroid Gland and Behavior. Society of Toxicology, Baltimore, MD, March 12 - 16, 2017.

Impact/Purpose:

Society of Toxicology abstract for a poster presentation on the effects of the perflorinated chemical, perflorohexane sulfonate, on thyroid hormones and brain development

Description:

The developing mammalian central nervous system is dependent on thyroid hormones (TH) to control neurogenesis, differentiation and migration. In humans, low maternal serum thyroxine (T4) levels have been correlated to impaired child brain development. Perfluorinated chemicals are widely distributed xenobiotics with varying effects on TH. In this study, perfluorohexane sulfonate (PFHxS, 0, 0.05, 5 and 25 mg/kg/day, po) was administered to Wistar rat dams (n = 20/dose group) from gestation day (GD) 7 through postnatal day (PND) 22. No signs of overt toxicity were observed in the dams or the pups. Liver weights were not affected in the dams or male pups on PND 16, but mild increases (3-6%) were detected in the female pups on PND 17 at 5 and 25 mg/kg/day. In the 5 and 25 mg/kg/day groups serum T4 was reduced to 80 and 60 % of control as early as GD 15, and at PND 22 dams were down to 60 and 30 % of control. Offspring were assessed at PND16/17 where serum T4 were reduced to 70 and 55 % of control in the 5 and 25 mg/kg/day dose groups. Despite reductions in serum TH, thyroid gland weights were not increased in dams or pups. Neither were the transcriptional levels of Tpo, Nis, Nkx2 or TshR altered in the thyroid gland of pups at PND17 suggesting a lack of activation of the hypothalamic-pituitary-thyroid axis. Motor activity assessed on PND 27 and PND 115 (n=15-19/dose/sex/age) was not dose dependently affected by exposure to PFHxS, but there was a lack of sex difference in the 0.05 mg/kg/day group. The data suggest that the reductions in serum hormone induced by PFHxS do not appear to alter TH via an action on the thyroid gland or by enzyme induction in the liver. Further investigations of the mechanisms whereby PFHxS reduces serum TH, its toxicological profile, and its potential to induce developmental neurotoxicity are warranted. Does not reflect EPA policy

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