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斯普拉格-道利大鼠吸入全氟辛烷磺酸氟化物(POSF)后的毒理学反应。

Toxicological response of Sprague Dawley rats from inhalation exposure to perfluorooctane sulfonyl fluoride (POSF).

作者信息

Butenhoff John L, Olsen Geary W, Chang Sue

机构信息

3M Company, Medical Department,Building 220-6W-08, St. Paul, MN 55144, USA.

出版信息

Toxicol Lett. 2017 Apr 5;271:38-49. doi: 10.1016/j.toxlet.2017.02.017. Epub 2017 Feb 27.

Abstract

Perfluorooctane sulfonyl fluoride (POSF) was a volatile starting material in the production of perfluorooctane sulfonate (PFOS), a stable surfactant that has been extensively studied due to its ubiquitous environmental distribution and slow clearance in humans. Because the inhalation toxicity of POSF on repeated exposure has not been previously reported, the current study evaluated the inhalation toxicity of POSF at 30, 100, and 300ppm (v/v) in rats for up to 13 weeks with a four-week recovery period. The extent of PFOS formation was also measured because POSF hydrolyzed to form PFOS. In addition, detailed urinalysis and examination of the urinary bladder were included to determine if factors associated with the development of bladder cancer were present. Exposure to POSF at 300ppm was associated with reduction in body weight-gain, necrosis of laryngeal cartilage, increased lung and bronchi weight with septal thickening, and changes in alveolar macrophages. The microscopic observations in larynx and lung are consistent with likely hydrolysis of POSF to form hydrogen fluoride (HF). Exposure to POSF at 100 and 300ppm was associated with increased relative liver weight, hepatocellular hypertrophy (except for females exposed to 100ppm POSF), and lowering of serum cholesterol (male only). After 13 weeks of exposure to 30, 100, or 300ppm POSF, serum PFOS concentration approximated 7, 35, or 100μg/mL, respectively. Approximately 0.1% of inhaled POSF was converted to PFOS. No changes indicative of bladder effects were observed in these rats exposed to POSF at any dose.

摘要

全氟辛烷磺酰氟(POSF)是生产全氟辛烷磺酸(PFOS)的挥发性起始原料,PFOS是一种稳定的表面活性剂,因其在环境中广泛分布且在人体内清除缓慢而受到广泛研究。由于此前尚未报道过重复接触POSF的吸入毒性,本研究评估了大鼠在30、100和300ppm(v/v)浓度下吸入POSF长达13周并伴有4周恢复期时的吸入毒性。由于POSF会水解形成PFOS,因此还测量了PFOS的生成程度。此外,还进行了详细的尿液分析和膀胱检查,以确定是否存在与膀胱癌发生相关的因素。暴露于300ppm的POSF会导致体重增加减少、喉软骨坏死、肺和支气管重量增加并伴有间隔增厚,以及肺泡巨噬细胞发生变化。在喉部和肺部的显微镜观察结果与POSF可能水解形成氟化氢(HF)一致。暴露于100和300ppm的POSF会导致相对肝脏重量增加、肝细胞肥大(暴露于100ppm POSF的雌性大鼠除外),以及血清胆固醇降低(仅雄性)。在暴露于30、100或300ppm POSF 13周后,血清PFOS浓度分别约为7、35或100μg/mL。吸入的POSF约有0.1%转化为PFOS。在这些接受任何剂量POSF暴露的大鼠中,未观察到表明膀胱有影响的变化。

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