Van Rafelghem M J, Inhorn S L, Peterson R E
Toxicol Appl Pharmacol. 1987 Mar 15;87(3):430-9. doi: 10.1016/0041-008x(87)90248-1.
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.
用毒性剂量的全氟癸酸（PFDA）处理大鼠会导致采食量、体重、血清甲状腺素（T4）和三碘甲状腺原氨酸（T3）浓度、静息心率以及体温降低。其中一些效应类似于甲状腺功能减退的特征性变化。因此，研究了PFDA对甲状腺功能状态的影响，以将甲状腺状态的变化与PFDA毒性体征联系起来。在本研究中，研究了PFDA对血浆甲状腺激素浓度和一些甲状腺状态指标的剂量相关效应，并与PFDA毒性体征进行了比较。给年轻成年雄性Sprague-Dawley大鼠单次腹腔注射PFDA（20、40或80mg/kg），给药7天后评估后续变化。体重和采食量的降低被用作PFDA毒性的指标，范围从轻微到严重。所有剂量下血浆T4浓度和游离甲状腺素指数均大幅降低，仅在高剂量PFDA（80mg/kg）下通过配对喂食可模拟这些变化。PFDA处理未影响血浆T3浓度，而高剂量水平（80mg PFDA/kg）的配对喂食导致T3显著降低（比无限制喂食对照组降低约50%）。尽管PFDA导致甲状腺重量呈剂量依赖性降低，但配对喂食并未完全与之平行，甲状腺组织学未见明显异常。PFDA处理导致基础代谢率略有降低（80mg PFDA/kg时降低8%）。在与80mg PFDA/kg剂量组大鼠配对喂食的溶媒处理对照组中，观察到基础代谢率有更大幅度的降低（约18%）。通过耗氧量和体核温度测量的产热不受PFDA处理的显著影响，这些变化与配对喂食平行。低剂量PFDA（20mg/kg）时血浆T4浓度和游离甲状腺素指数的降低表明，PFDA诱导的甲状腺素血症可与其在较高剂量下观察到的明显毒性效应（即严重摄食减少和体重减轻）相分离。此处获得的结果表明，尽管血浆甲状腺激素水平发生了改变，但对甲状腺功能状态并没有一致的影响模式可以解释PFDA的明显毒性。
