Effects of perfluorodecanoic acid on thyroid status in rats

Treatment of rats with toxic doses of perfluorodecanoic acid (PFDA) results in reduction in feed intake, body weight, serum thyroxine (T4) and triiodothyronine (T3) concentrations, resting heart rates, and body temperatures. Some of these effects resemble changes characteristic of hypothyroidism. Therefore the effects of PFDA on functional thyroid status were examined to relate changes in thyroid status with signs of PFDA toxicity. In the present study, the dose-related effects of PFDA on plasma thyroid hormone concentrations and a number of indices of thyroid status were investigated and compared with signs of PFDA toxicity. Young adult male Sprague-Dawley rats were given single intraperitoneal doses of PFDA (20, 40, or 80 mg/kg), and subsequent changes were evaluated 7 days after dosing. Decreases in body weight and feed intake were used as measures of PFDA toxicity and ranged from minimal to severe. Plasma T4 concentrations and free thyroxine index were drastically reduced at all doses, and these changes were mimicked by pair feeding only at the high dose of PFDA (80 mg/kg). Plasma T3 concentrations were not affected by PFDA treatment, whereas pair feeding at the high-dose level (80 mg PFDA/kg) resulted in a significant reduction (ca. 50% from unlimited-fed control) in T3. Although PFDA caused a dose-dependent decrease in thyroid gland weight which was not completely paralleled by pair feeding, thyroid histology was unremarkable. PFDA treatment resulted in a small decrease in basal metabolic rate (8% at 80 mg PFDA/kg). A greater reduction (ca. 18%) in basal metabolic rate was observed in vehicle-treated controls pair-fed to rats of the 80 mg PFDA/kg dose group. Thermogenesis, as measured by oxygen consumption and body core temperatures, was not greatly affected by PFDA treatment, and these changes were paralleled by pair feeding. Reductions in plasma T4 concentration and free thyroxine index at a low dose of PFDA (20 mg/kg) indicate that PFDA-induced hypothyroxinemia can be dissociated from its overtly toxic effects (i.e., severe hypophagia and body weight loss) observed at higher doses. The results obtained here suggest that despite alterations in plasma thyroid hormone levels there is no consistent pattern of effects on functional thyroid status which could explain the overt toxicity of PFDA.