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Subacute dermal toxicity of perfluoroalkyl carboxylic acids: comparison with different carbon-chain lengths in human skin equivalents and systemic effects of perfluoroheptanoic acid in Sprague Dawley rats.
Archives of Toxicology ( IF 6.1 ) Pub Date : 2019-12-03 , DOI: 10.1007/s00204-019-02634-z
Ji-Seok Han 1, 2 , Sumi Jang 1 , Hwa-Young Son 2 , Yong-Bum Kim 1 , Younhee Kim 1 , Jung-Ho Noh 1 , Mi-Jeong Kim 3 , Byoung-Seok Lee 1
Affiliation  

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are used in various fields but raise concerns regarding human health and environmental consequences. Among PFASs, perfluorooctanoic acid (PFOA) and short-chain perfluoroalkyl carboxylic acids (SC PFCAs) are detectable in skin-contact consumer products and have dermal absorption potential. Here, we investigated the effects of dermal exposure to PFOA and SC PFCAs using in vitro and in vivo models. Human skin equivalents were topically treated with 0.25 mM and 2.5 mM PFOA and SC PFCAs (perfluoropentanoic acid, PFPeA; perfluorohexanoic acid, PFHxA; and perfluoroheptanoic acid, PFHpA) for 6 days, and cell viability, interleukin (IL)-1α, oxidative stress markers (malondialdehyde, MDA; and 8-hydroxydeoxyguanosine, 8-OHdG), and histopathology were examined. MDA levels were significantly higher in the PFASs groups than in controls. Compared with SC PFCAs, 2.5 mM PFOA caused more IL-1α (p < 0.001) release, decreased skin thickness and microscopic abnormalities. To evaluate systemic effects, Sprague Dawley (SD) rats were dermally treated with 250 and 1000 mg/kg PFHpA for 2 weeks and clinical and anatomic pathology were assessed. At 1000 mg/kg, 83% of the rats died, with severe ulcerative dermatitis at the application site. Adverse PFHpA-treated systemic changes were observed in the kidney, liver and testes, and histopathologic lesions such as renal tubular necrosis, hepatocellular necrosis, and germ cell degeneration were seen at 250 and 1000 mg/kg. Our study suggests that SC PFCAs have fewer effects on the skin than PFOA, but SC PFCAs can have adverse effects on major organs with systemic exposure at high concentrations.

中文翻译:

全氟烷基羧酸的亚急性皮肤毒性:与人类皮肤当量中不同碳链长度的比较以及全氟庚酸在Sprague Dawley大鼠中的全身作用。

全氟烷基和多氟烷基物质(PFAS)已用于各个领域,但引起了对人类健康和环境后果的担忧。在全氟辛烷磺酸中,全氟辛酸(PFOA)和短链全氟烷基羧酸(SC PFCA)在与皮肤接触的消费产品中可检测到,并具有皮肤吸收潜力。在这里,我们使用体外和体内模型研究了皮肤暴露于PFOA和SC PFCA的影响。用0.25 mM和2.5 mM PFOA和SC PFCA(全氟戊酸PFPeA;全氟己酸,PFHxA;全氟庚酸,PFHpA)局部处理人体皮肤等效物6天,并测定细胞活力,白介素(IL)-1α,氧化应激检查了标志物(丙二醛,MDA;和8-羟基脱氧鸟苷,8-OHdG)和组织病理学。PFAS组的MDA水平明显高于对照组。与SC PFCA相比,2.5 mM PFOA导致更多的IL-1α释放(p <0.001),皮肤厚度减少和镜下异常。为了评估全身作用,用250和1000 mg / kg PFHpA皮肤处理Sprague Dawley(SD)大鼠2周,并评估临床和解剖病理学。剂量为1000 mg / kg时,有83%的大鼠死亡,其应用部位患有严重的溃疡性皮炎。在肾,肝和睾丸中观察到不良的PFHpA处理的全身性变化,并且以250和1000 mg / kg的剂量观察到组织病理学病变,例如肾小管坏死,肝细胞坏死和生殖细胞变性。我们的研究表明,SC PFCA对皮肤的影响比PFOA少,
更新日期:2019-12-03
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