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首页> 外文期刊>Journal of immunotoxicology. >Immunotoxic and hepatotoxic effects of perfluoro- n -decanoic acid (PFDA) on female Harlan Sprague–Dawley rats and B6C3F1/N mice when administered by oral gavage for 28 days
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Immunotoxic and hepatotoxic effects of perfluoro- n -decanoic acid (PFDA) on female Harlan Sprague–Dawley rats and B6C3F1/N mice when administered by oral gavage for 28 days

机译：全氟正癸酸（PFDA）对雌性Harlan Sprague–Dawley大鼠和B 6 C 3 F 1 /的免疫毒性和肝毒性作用N小鼠经口灌胃给药28天

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Abstract Poly- and perfluoroalkyl substances (PFAS) are chemically and thermally stable, hydrophobic, lipophobic compounds used in stain repellants and water and oil surfactants, and associated with immunosuppression and peroxisome proliferator activity. Perfluoro-n-decanoic acid (PFDA, (CF3(CF2)8COOH), a fluorinated straight chain fatty acid compound, is reported to induce thymic atrophy and reversible bone marrow hypocellularity in rodent models. The objective of this study was to assess potential immunotoxicity of PFDA, due to its structural similarity to other immunosuppressive PFASs. Female Harlan Sprague–Dawley rats were exposed to 0–2.0?mg PFDA/kg by oral gavage daily for 28?d. Female B6C3F1/N mice were exposed once/week to 0–5.0?mg PFDA/kg by gavage for 4?weeks. Animals were evaluated for effects on immune cell populations in spleen and bone marrow, and innate, humoral-, and cell-mediated immunity. Mice were also evaluated for resistance to Influenza virus. Treatment-related hepatocyte necrosis and hepatomegaly were observed in rats treated with 0.5?mg PFDA/kg/d. In mice, hepatomegaly (26–89%) was observed following exposure to ≥0.625?mg PFDA/kg/week, while splenic atrophy (20%) was observed at 5.0?mg PFDA/kg/week. At 5.0?mg PFDA/kg/week, total spleen cells, and Ig?+?and NK?+?cells were decreased (17.6–27%). At ≥ 1.25?mg PFDA/kg/week the numbers of splenic CD3+, CD4+, CD8+, and Mac3+ cells were decreased (10.5–39%). No changes were observed in leukocyte subpopulations in PFDA-exposed rats. Phagocytosis by fixed-tissue macrophages was decreased in liver (specific activity, 24–39%) at ≥0.25?mg PFDA/kg/d in rats. PFDA-induced effects on humoral- and cell-mediated immunity, host resistance, and bone marrow progenitor cells were limited. These data suggest that exposure to PFDA may induce adverse effects in rat liver in a manner consistent with the PFAS class, and may also alter the balance of immune cell populations in lymphoid tissues in mice.
机译：摘要聚全氟烷基物质（PFAS）是化学和热稳定的疏水性疏脂化合物，用于防污剂，水和油表面活性剂，并具有免疫抑制作用和过氧化物酶体增殖物活性。全氟正癸酸（PFDA，（CF 3 （CF 2 ） 8 COOH）是一种氟化的直链脂肪酸化合物，据报道，在啮齿类动物模型中，胸腺萎缩和可逆性骨髓细胞功能低下，本研究的目的是评估PFDA与其他免疫抑制PFAS结构相似的潜在免疫毒性，雌性Harlan Sprague–Dawley大鼠暴露于0–2.0？每天经口灌胃每天一次200 mg PFDA / kg，每天对雌性B 6 C 3 F 1 / N小鼠暴露一次。连续灌胃4周，每次0-5.0 mg PFDA / kg，评估动物对脾脏和骨髓中免疫细胞群以及先天，体液和细胞介导的免疫的影响，还评估了小鼠对流感的抵抗力用0.5？mg PFDA / kg / d治疗的大鼠中观察到治疗相关的肝细胞坏死和肝肿大;暴露于≥0.625？mg PFDA / kg /周的小鼠中观察到肝肿大（26–89％），而锦绣以5.0？mg PFDA / kg /周观察到IC萎缩（20％）。 PFDA为5.0？mg / kg /周时，总脾细胞以及Ig ++和NK ++细胞减少（17.6–27％）。 PFDA≥1.25 mg / kg /周时，脾脏CD3 + ，CD4 + ，CD8 + 和Mac3 + 细胞减少（10.5–39％）。在暴露于PFDA的大鼠中，白细胞亚群未见变化。在大鼠中，≥0.25？mg PFDA / kg / d时，肝脏中固定组织巨噬细胞的吞噬作用降低（比活性，24-39％）。 PFDA诱导的对体液和细胞介导的免疫，宿主抗性以及骨髓祖细胞的作用是有限的。这些数据表明，暴露于PFDA可能以与PFAS分类一致的方式在大鼠肝脏中引起不良反应，并且还可能改变小鼠淋巴组织中免疫细胞群的平衡。

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