National Food Institute, Technical University of Denmark, Kemitorvet Building 202, 2800 Kgs. Lyngby, Denmark.
Centre for Arctic Health & Molecular Epidemiology, Department of Public Health, Aarhus University, Denmark; Greenland's Centre for Health Research, University of Greenland, Nuuk, Greenland.
Environ Int. 2021 Jan;146:106191. doi: 10.1016/j.envint.2020.106191. Epub 2020 Oct 14.
Humans are exposed to a large number of chemicals from sources such as the environment, food, and consumer products. There is growing concern that human exposure to chemical mixtures, especially during critical periods of development, increases the risk of adverse health effects in newborns or later in life. Historically, the one-chemical-at-a-time approach has been applied both for exposure assessment and hazard characterisation, leading to insufficient knowledge about human health effects caused by exposure to mixtures of chemicals that have the same target. To circumvent this challenge researchers can apply in vitro assays to analyse both exposure to and human health effects of chemical mixtures in biological samples. The advantages of using in vitro assays are: (i) that an integrated effect is measured, taking combined mixture effects into account and (ii) that in vitro assays can reduce complexity in identification of Chemicals of Emerging Concern (CECs) in human tissues. We have reviewed the state-of-the-art on the use of receptor-based in vitro assays to assess human exposure to chemical mixtures and related health impacts. A total of 43 studies were identified, in which endpoints for the arylhydrocarbon receptor (AhR), the estrogen receptor (ER), and the androgen receptor (AR) were used. The majority of studies reported biological activities that could be associated with breast cancer incidence, male reproductive health effects, developmental toxicities, human demographic characteristics or lifestyle factors such as dietary patterns. A few studies used the bioactivities to check the coverage of the chemical analyses of the human samples, whereas in vitro assays have so far not regularly been used for identifying CECs in human samples, but rather in environmental matrices or food packaging materials. A huge field of novel applications using receptor-based in vitro assays for mixture toxicity assessment on human samples and effect-directed analysis (EDA) using high resolution mass spectrometry (HRMS) for identification of toxic compounds waits for exploration. In the future this could lead to a paradigm shift in the way we unravel adverse human health effects caused by chemical mixtures.
人类会从环境、食物和消费产品等各种来源接触到大量的化学物质。越来越多的人担心，人类接触化学混合物（尤其是在发育关键期）会增加新生儿或以后生活中出现不良健康影响的风险。从历史上看，人们在进行暴露评估和危害特征描述时，一直采用逐个化学物质的方法，这导致人们对因接触具有相同靶标的化学混合物而导致的人类健康影响了解不足。为了应对这一挑战，研究人员可以应用体外检测方法来分析生物样本中的化学混合物暴露和对人类健康的影响。使用体外检测方法具有以下优势：（i）可以测量综合效应，考虑到混合物的综合效应；（ii）可以减少鉴定人类组织中新兴关注化学物质（CECs）的复杂性。我们综述了基于受体的体外检测方法在评估人类接触化学混合物和相关健康影响中的最新应用。共确定了 43 项研究，其中使用了芳香烃受体 (AhR)、雌激素受体 (ER) 和雄激素受体 (AR) 作为终点。大多数研究报告了与乳腺癌发病率、男性生殖健康影响、发育毒性、人类人口统计学特征或生活方式因素（如饮食模式）相关的生物活性。少数研究使用生物活性来检查人体样本的化学分析的覆盖范围，而到目前为止，体外检测方法尚未被常规用于鉴定人体样本中的 CECs，而是更多地用于环境基质或食品包装材料中。使用基于受体的体外检测方法评估人体样本的混合物毒性和使用高分辨率质谱 (HRMS) 进行基于效应的分析 (EDA) 以鉴定有毒化合物的新应用领域广阔，等待探索。未来，这可能会改变我们揭示化学混合物引起的不良人类健康影响的方式。
