Baumer Andreas, Jäsch Sandra, Ulrich Nadin, Bechmann Ingo, Landmann Julia, Stöver Andreas, Escher Beate I
Department Cell Toxicology, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
Department Analytical Environmental Chemistry, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
Environ Int. 2021 Dec;157:106867. doi: 10.1016/j.envint.2021.106867. Epub 2021 Sep 16.
Passive equilibrium sampling of chemical mixtures from different human post-mortem tissues (liver, brain (cerebrum and cerebellum), adipose tissue) and blood was combined with instrumental analysis using direct sample introduction (DSI) GC-MS/MS and bioanalytical profiling using in vitro bioassays targeting the activation of the aryl hydrocarbon receptor (AhR-CALUX), the adaptive stress response (AREc32) and cytotoxicity. The tissues stemmed from pathology samples collected in two German cities and covered males and females aged 21 to 100 with a mean age of 67 years. Neutral organic chemicals were extracted using polydimethylsiloxane (PDMS) at mass ratios of tissue to PDMS of approximately 6 for blood, 3 for adipose tissue and 10 for liver and brain. Amounts of chemicals in PDMS were converted to lipid-associated concentrations using previously measured partition constants that were chemical-independent despite covering eight orders of magnitude in hydrophobicity. Up to 35 of 99 targeted chemicals were detected in 6 tissues of 16 individuals (88 samples in total), among them legacy persistent organic pollutants (POP) such as DDT and derivatives and polychlorinated biphenyls (PCB) but also modern pesticides and chemicals present in consumer products. POPs were highest in adipose tissue and lipid-associated concentrations increased with age, while concentrations of fragrance materials such as galaxolide were independent of age. In tissues from the same individual, chemical concentrations mostly increased from similar levels in brain and blood to higher levels in liver and highest in adipose tissue. However, easily degradable chemicals such as phenanthrene were mainly detected in blood and brain, and very hydrophilic chemicals were least abundant in adipose tissue. The passive sampling method allows a direct comparison of chemical burden between different tissues and may have forensic applications, for example to study internal distributions or to use one tissue type as a proxy for others. The sum of concentrations of the detected chemicals was positively correlated with the bioassay responses but mixture modeling showed that the detected chemicals explained less than 2% of the activation of the AhR and less than 0.5% of cytotoxicity. This means that more than 10,000 chemicals would need to be included in an analytical method to capture all the effects with many chemicals potentially being below detection limits but still contributing to mixture effects. Therefore, we propose a smart combination of chemical analysis and bioassays to quantify priority chemicals but use bioassay responses as effect-scaled concentrations to capture the entire exposome in future epidemiological studies.
采用直接进样（DSI）气相色谱-串联质谱（GC-MS/MS）进行仪器分析，并使用针对芳烃受体（AhR-CALUX）激活、适应性应激反应（AREc32）和细胞毒性的体外生物测定进行生物分析谱分析，对来自不同人体尸检组织（肝脏、大脑（大脑和小脑）、脂肪组织）和血液的化学混合物进行被动平衡采样。这些组织来源于在德国两个城市收集的病理样本，涵盖了年龄在21至100岁之间的男性和女性，平均年龄为67岁。使用聚二甲基硅氧烷（PDMS）以组织与PDMS的质量比分别约为血液6、脂肪组织3、肝脏和大脑10来提取中性有机化学物质。尽管所涉及的化学物质疏水性跨越八个数量级，但利用先前测量的与化学物质无关的分配常数，将PDMS中化学物质的量转换为与脂质相关的浓度。在16名个体的6种组织（共88个样本）中检测到了99种目标化学物质中的多达35种，其中包括诸如滴滴涕及其衍生物和多氯联苯（PCB）等遗留持久性有机污染物（POP），还有现代农药和消费品中存在的化学物质。POPs在脂肪组织中含量最高，且与脂质相关的浓度随年龄增加，而诸如佳乐麝香等香料物质的浓度与年龄无关。在同一个体的组织中，化学物质浓度大多从大脑和血液中的相似水平增加到肝脏中的较高水平，在脂肪组织中最高。然而，诸如菲等易降解化学物质主要在血液和大脑中被检测到，而亲水性很强的化学物质在脂肪组织中含量最少。被动采样方法允许直接比较不同组织之间的化学负荷，并且可能具有法医应用，例如用于研究体内分布或使用一种组织类型作为其他组织的替代物。检测到的化学物质浓度总和与生物测定反应呈正相关，但混合物建模表明，检测到的化学物质对AhR激活的解释不到2%，对细胞毒性的解释不到0.5%。这意味着一种分析方法需要纳入超过10,000种化学物质才能捕捉所有效应，许多化学物质可能低于检测限，但仍对混合物效应有贡献。因此，我们建议将化学分析和生物测定巧妙结合，以量化优先化学物质，但使用生物测定反应作为效应缩放浓度，以便在未来的流行病学研究中捕捉整个暴露组。
