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首页> 外文会议>Annual conference of the International Society of Exposure Science >Prenatal and Early Childhood Exposure to Multi-class Organic Chemicals Using Tooth-Matrix Biomarkers
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Prenatal and Early Childhood Exposure to Multi-class Organic Chemicals Using Tooth-Matrix Biomarkers

机译：产前和幼儿期使用牙基质生物标记物接触多种有机化学品

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The exposome concept proposes a comprehensive assessment of environmental exposures from the prenatal period onwards. For decades, teeth have been used to estimate long-term cumulative exposure to metals. Recently developed high-dimensional analytical methods that combine sophisticated histological and chemical analysis to precisely sample tooth layers that correspond to specific life stages have the potential to reconstruct the exposome in the second and third trimesters of prenatal development and during early childhood. We reconstructed the prenatal and early childhood exposure to multiple organic chemical classes using teeth. We performed global screening of small molecules in trimester-specific formed dentine layers from deciduous teeth using liquid chromatography coupled quadrupole time-of-flight mass spectrometry (QTOF-LC/MS) metabolomics approach. QTOF-LC/MS analyses showed unique and differential chemical signatures of environmental exposure that are individual and development-stage dependent. The results of this study (a) revealed more than 12,000 unique chemical signatures in trimester-specific dentine layers, (b) indicate high inter- and intra-child variability in screened chemical profiles, (c) show novel 'known unknowns' and 'suspected unknowns' compounds, (d) demonstrate exposure misclassification error that can cause misleading inferences about causality, and (e) most importantly, the reconstruction of exposure was done 7 to 10 years after prenatal and early childhood exposure. The chemicals detected included phenols (BPA, BPS, BPF), phthalate metabolites, parabens, tobacco markers (cotinine and nicotine). Validation of key signatures is underway. Specifically, phthalate monsters detected in children's deciduous teeth are being compared to levels in maternal urine during pregnancy. Similarly, analysis are also underway for perfluorinated compounds. A retrospective temporal exposomic approach that precisely measures exposure intensity and timing during prenatal and early childhood development would substantially aid epidemiologic investigations, particularly case-control studies of rare health outcomes.
机译：暴露概念提出了从产前开始的环境暴露的综合评估。几十年来，人们一直在使用牙齿来估计长期累积的金属暴露量。最近开发的将复杂的组织学和化学分析相结合的高维分析方法，可以精确地采样与特定生命阶段相对应的牙齿层，从而有可能在产前和孕中期和幼儿期重建外露体。我们使用牙齿重建了产前和儿童早期接触多种有机化学物质的类别。我们使用液相色谱-四极杆飞行时间质谱（QTOF-LC / MS）代谢组学方法对从乳牙中的三个月特定形成的牙本质层中的小分子进行了全局筛选。 QTOF-LC / MS分析显示了环境暴露的独特和差异化学特征，这些特征是独立的，且与开发阶段有关。这项研究的结果（a）显示了三个月以上的特定牙本质层中有超过12,000个独特的化学特征，（b）表明筛选出的化学特征中儿童之间和儿童内部的高度变异性，（c）显示了新颖的“已知未知物”和“可疑未知化合物，（d）显示暴露分类错误，可能引起对因果关系的误导性推论，（e）最重要的是，在产前和儿童早期暴露后7至10年进行暴露的重建。检测到的化学物质包括苯酚（BPA，BPS，BPF），邻苯二甲酸酯代谢物，对羟基苯甲酸酯，烟草标记（可卡因和尼古丁）。密钥签名的验证正在进行中。具体来说，正在对儿童乳牙中检测到的邻苯二甲酸酯怪物与孕妇孕期尿液中的水平进行比较。同样，全氟化合物的分析也在进行中。回顾性的时间暴露组学方法可精确测量产前和儿童早期发育过程中的暴露强度和时间安排，将大大有助于流行病学调查，尤其是对罕见健康结局​​的病例对照研究。

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