Abstract

Perfluoroalkyl substances (PFASs) are a complex group of man-made chemicals with high stability and mobility leading to ubiquitous environmental contamination and accumulation in the food chain. In human serum/plasma samples, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are the lead compounds. They are immunotoxic in experimental animals, and epidemiological studies provided evidence of a diminished production of vaccine antibodies in young children. However, information on children of the first year of age is missing but relevant, as they have a relatively high exposure if breastfed, and may have a higher susceptibility as their immune system is developing. In a cross-sectional study with 101 healthy 1-year-old children, internal levels of persistent organic pollutants and a broad panel of biological parameters were investigated at the end of the 1990s. Additional analysis of PFASs resulted in plasma levels (mean ± SD) of PFOA and PFOS of 3.8 ± 1.1 and 6.8 ± 3.4 µg/L, respectively, in the 21 formula-fed children, and of 16.8 ± 6.6 and 15.2 ± 6.9 µg/L in the 80 children exclusively breastfed for at least 4 months. The study revealed significant associations between levels of PFOA, but not of PFOS, and adjusted levels of vaccine antibodies against Haemophilus influenza type b (Hib, r = 0.32), tetanus (r = 0.25) and diphtheria (r = 0.23), with no observed adverse effect concentrations (NOAECs) determined by fitting a ‘knee’ function of 12.2, 16.9 and 16.2 µg/L, respectively. The effect size (means for PFOA quintiles Q1 vs. Q5) was quantified to be − 86, − 54 and − 53%, respectively. Furthermore, levels of PFOA were inversely associated with the interferon gamma (IFNɣ) production of ex-vivo lymphocytes after stimulation with tetanus and diphtheria toxoid, with an effect size of − 64 and − 59% (means Q1 vs. Q5), respectively. The study revealed no influence of PFOA and PFOS on infections during the first year of life and on levels of cholesterol. Our results confirmed the negative associations of PFAS levels and parameters of immune response observed in other epidemiological studies, with high consistency as well as comparable NOAECs and effects sizes for the three vaccine antibodies investigated, but for PFOA only. Due to reduction of background levels of PFASs during the last 20 years, children in Germany nowadays breastfed for a long duration are for the most part not expected to reach PFOA levels at the end of the breastfeeding period above the NOAECs determined.

中文翻译：

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内部暴露于101名1岁健康儿童的全氟烷基物质（PFAS）和生物学标志物：全氟辛酸（PFOA）水平与疫苗反应之间的关联。

摘要

全氟烷基物质（PFAS）是一组复杂的人造化学品，具有高度的稳定性和移动性，导致普遍存在的环境污染和食物链中的积累。在人血清/血浆样品中，全氟辛酸（PFOA）和全氟辛烷磺酸盐（PFOS）是主要化合物。它们在实验动物中具有免疫毒性，流行病学研究提供了在幼儿中减少疫苗抗体产生的证据。但是，关于第一岁儿童的信息却缺少但很相关，因为如果母乳喂养，他们的暴露量相对较高，并且随着他们免疫系统的发展，他们的敏感性更高。在对101名1岁健康儿童的横断面研究中，在1990年代末对持久性有机污染物的内部水平和广泛的生物学参数进行了调查。对PFAS进行进一步分析后，在21名配方奶粉喂养的儿童中，PFOA和PFOS的血浆水平（平均值±SD）分别为3.8±1.1和6.8±3.4μg/ L，分别为16.8±6.6和15.2±6.9​​μg/ L在80个孩子中，有L个仅用母乳喂养了至少4个月。该研究表明PFOA水平（而非PFOS水平）与针对乙型流感嗜血杆菌（Hib，r  = 0.32），破伤风（r  = 0.25）和白喉（r = 0.23），而没有通过分别设置12.2、16.9和16.2 µg / L的“膝盖”功能确定的观察到的不良反应浓度（NOAEC）。影响大小（PFOA五分位数Q1与Q5的平均值）被量化为分别为-86％，-54％和-53％。此外，在破伤风和白喉类毒素刺激后，PFOA的水平与体外淋巴细胞的干扰素γ（IFNɣ）产生呈负相关，影响大小分别为-64％和-59％（分别为Q1与Q5）。该研究表明PFOA和PFOS对生命第一年的感染和胆固醇水平没有影响。我们的结果证实了其他流行病学研究中观察到的PFAS水平与免疫反应参数之间存在负相关关系，对三种被研究的疫苗抗体具有很高的一致性以及可比的NOAEC和效应大小，但仅限于PFOA。由于近20年来PFAS的本底水平降低，如今，在德国，长期进行母乳喂养的儿童在母乳喂养期结束时绝大部分都不会超过确定的NOAEC达到PFOA水平。