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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101 名健康 1 岁儿童体内全氟烷基物质 (PFAS) 和生物标记物的暴露：全氟辛酸 (PFOA) 水平与疫苗反应之间的关联。

 抽象的

全氟烷基物质（PFAS）是一组复杂的人造化学品，具有高稳定性和流动性，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 (PFOS) 是主要化合物。它们对实验动物具有免疫毒性，流行病学研究提供了幼儿疫苗抗体产生减少的证据。然而，关于一岁儿童的信息缺失但相关，因为如果母乳喂养，他们的暴露程度相对较高，并且随着他们的免疫系统的发育，可能具有更高的易感性。 20 世纪 90 年代末，一项针对 101 名健康 1 岁儿童的横断面研究对持久性有机污染物的内部水平和广泛的生物参数进行了调查。对 PFAS 的进一步分析得出，21 名配方奶喂养儿童的 PFOA 和 PFOS 血浆水平（平均值±标准差）分别为 3.8 ± 1.1 和 6.8 ± 3.4 µg/L，以及 16.8 ± 6.6 和 15.2 ± 6.9 µg/L。 L 是 80 名纯母乳喂养至少 4 个月的儿童。该研究揭示了 PFOA 水平（而非 PFOS）与 B 型流感嗜血杆菌(Hib， r = 0.32)、破伤风 ( r = 0.25) 和白喉 ( r = 0.23) 疫苗抗体调整水平之间存在显着相关性，且没有相关性。观察到的不良反应浓度 (NOAEC) 通过拟合“膝”函数分别确定为 12.2、16.9 和 16.2 µg/L。效应大小（PFOA 五分位数 Q1 与 Q5 的平均值）分别量化为 - 86、- 54 和 - 53%。 此外，PFOA 水平与破伤风和白喉类毒素刺激后离体淋巴细胞的干扰素 γ (IFNɣ) 产生呈负相关，效应大小分别为 - 64% 和 - 59%（平均 Q1 与 Q5）。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的负相关关系，对于所研究的三种疫苗抗体（但仅针对 PFOA）具有高度一致性以及可比较的 NOAEC 和效应大小。由于过去 20 年来 PFAS 背景水平有所下降，目前长期母乳喂养的德国儿童在母乳喂养期结束时预计大部分 PFOA 水平不会高于确定的 NOAEC。