Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
German Environment Agency (UBA), Corrensplatz 1, 14195, Berlin, Germany.
Int J Hyg Environ Health. 2022 Aug;245:114010. doi: 10.1016/j.ijheh.2022.114010. Epub 2022 Aug 5.
Nonylphenol (NP) is a high production volume chemical with a wide range of uses, e.g. in NP ethoxylates (NPEO). NP and NPEO have become ubiquitous in the environment and are considered of concern due to their general ecotoxicity and endocrine disrupting properties. However, knowledge on human exposure is scarce. In this study, we analyzed novel NP metabolites (OH-NP and oxo-NP) as robust biomarkers of exposure in 24h-urine samples from the German Environmental Specimen Bank (ESB). This enables us to reliably determine the individual NP body burden and to retrospectively evaluate NP exposure over the past 30 years. We analyzed 660 urine samples from eleven sampling years between 1991 and 2021. All samples were from young German adults between 20 and 29 years of age. OH-NP was quantifiable in all samples until 2017. In 2019 and 2021, the frequency of samples above the LOQ dropped to 90% and 77%, respectively. Median OH-NP concentrations significantly decreased from 4.32 μg/L in 1991 to 0.70 μg/L in 2021. OH-NP and oxo-NP levels correlated strongly, but oxo-NP concentrations and detections were considerably lower, in line with its known lower metabolic conversion. Reverse dosimetry back-calculated daily intakes (DI) of NP, based on OH-NP, decreased by almost a factor of four from medians of 0.16 μg/(kg bwd) in 1991 to 0.04 μg/(kg bwd) in 2021, respectively. The major drop took place only after 2012. This came as a surprise, because strict restrictions had been enacted much earlier in the EU, in 2003. All NP DIs were below the provisional tolerable daily intake of 5 μg/(kg bw*d) from the Danish Environmental Agency. DIs back-calculated from the ESB biomonitoring data agree well with calculations from food. This indicates to contaminated foodstuff as a major source of exposure. The time lag of regulatory restrictions to decreasing human exposure levels, the general lack of knowledge on exposure levels in susceptible populations such as children, and the ongoing worldwide use of NP underline the urgent need to continue monitoring NP exposures in Germany and worldwide. With these novel NP biomarkers, we provide a robust and sensitive tool for exposure and risk assessments, complementing environmental monitoring.
壬基酚（NP）是一种高产量的化学品，用途广泛，例如 NP 乙氧基化物（NPEO）。NP 和 NPEO 已经在环境中无处不在，由于其普遍的生态毒性和内分泌干扰特性而被认为令人担忧。然而，人类接触的知识却很少。在这项研究中，我们分析了新型 NP 代谢物（OH-NP 和 oxo-NP）作为德国环境标本库（ESB）中 24 小时尿液样本中暴露的可靠生物标志物。这使我们能够可靠地确定个体 NP 体负荷，并追溯性地评估过去 30 年的 NP 暴露情况。我们分析了 1991 年至 2021 年 11 个采样年的 660 个尿液样本。所有样本均来自 20 至 29 岁的年轻德国成年人。OH-NP 可在所有样本中定量，直至 2017 年。2019 年和 2021 年，超过 LOQ 的样本频率分别降至 90%和 77%。1991 年的 4.32μg/L 中位数显著下降到 2021 年的 0.70μg/L。OH-NP 和 oxo-NP 水平密切相关，但 oxo-NP 浓度和检测值要低得多，与已知的较低代谢转化率相符。基于 OH-NP 反剂量法推算的 NP 日摄入量（DI），从 1991 年的中位数 0.16μg/（kg bwd）下降近四分之三，至 2021 年的 0.04μg/（kg bwd）。这一主要下降仅发生在 2012 年之后。这令人惊讶，因为欧盟早在 2003 年就对其实施了更严格的限制。所有 NP DI 均低于丹麦环境署规定的暂定可耐受日摄入量 5μg/（kg bw*d）。从 ESB 生物监测数据推算的 DI 与从食物推算的 DI 非常吻合。这表明受污染的食物是暴露的主要来源。监管限制对降低人类暴露水平的时间滞后，以及儿童等易感人群暴露水平的普遍缺乏了解，以及 NP 在全球范围内的持续使用，都突显了继续在德国和全球范围内监测 NP 暴露的迫切需要。有了这些新型 NP 生物标志物，我们为暴露和风险评估提供了一种可靠和敏感的工具，补充了环境监测。
