Environmental factors contribute to the risk for adverse health outcomes against a background of genetic predisposition. Among these factors, chemical exposures may substantially contribute to disease risk and adverse outcomes. In fact, epidemiological cohort studies have established associations between exposure against individual chemicals and adverse health effects. Yet, in daily life individuals are exposed to complex mixtures in varying compositions. To capture the totality of environmental exposures the concept of the exposome has been developed. Here, we undertake an overview of major exposome projects, which pioneered the field of exposomics and explored the links between chemical exposure and health outcomes using cohort studies. We seek to reflect their achievements with regard to (i) capturing a comprehensive picture of the environmental chemical exposome, (ii) aggregating internal exposures using chemical and bioanalytical means of detection, and (iii) identifying associations that provide novel options for risk assessment and intervention. Various complementary approaches can be distinguished in addressing relevant exposure routes and it emerges that individual exposure histories may not easily be grouped. The number of chemicals for which human exposure can be detected is substantial and highlights the reality of mixture exposures. Yet, to a large extent it depends on targeted chemical analysis with the specific challenges to capture all relevant exposure routes and assess the chemical concentrations occurring in humans. The currently used approaches imply prior knowledge or hypotheses about relevant exposures. Typically, the number of chemicals considered in exposome projects is counted in dozens—in contrast to the several thousands of chemicals for which occurrence have been reported in human serum and urine. Furthermore, health outcomes are often still compared to single chemicals only. Moreover, explicit consideration of mixture effects and the interrelations between different outcomes to support causal relationships and identify risk drivers in complex mixtures remain underdeveloped and call for specifically designed exposome-cohort studies.

在遗传倾向的背景下，环境因素会增加不良健康结果的风险。在这些因素中，化学品暴露可能会极大地增加疾病风险和不良后果。事实上，流行病学队列研究已经确定了接触个别化学物质与不良健康影响之间的关联。然而，在日常生活中，人们会接触到不同成分的复杂混合物。为了捕获环境暴露的总体情况，开发了暴露组的概念。在这里，我们对主要的暴露组项目进行了概述，这些项目开创了暴露组学领域，并利用队列研究探索了化学品暴露与健康结果之间的联系。我们力求反映他们在以下方面取得的成就：(i) 捕获环境化学暴露的全面情况，(ii) 使用化学和生物分析检测手段汇总内部暴露，以及 (iii) 识别为风险评估和风险评估提供新选择的关联。干涉。在解决相关暴露途径时可以区分各种互补方法，并且个体暴露历史可能不容易分组。可检测到人体接触的化学物质数量巨大，凸显了混合物接触的现实。然而，在很大程度上，这取决于有针对性的化学分析，以及捕获所有相关暴露途径并评估人体中发生的化学浓度的具体挑战。当前使用的方法意味着有关相关暴露的先验知识或假设。 通常，暴露组项目中考虑的化学物质数量为数十种，相比之下，人类血清和尿液中报告的化学物质数量为数千种。此外，健康结果通常仍仅与单一化学品进行比较。此外，明确考虑混合物效应和不同结果之间的相互关系以支持因果关系并识别复杂混合物中的风险驱动因素仍然不发达，需要专门设计的暴露组研究。