Receptor-based in vitro activities to assess human exposure to chemical mixtures and related health impacts

• Published in: Environment international 2021-01, Vol.146, p.106191-18, Article 106191
• Main Authors: Vinggaard, Anne Marie, Bonefeld-Jørgensen, Eva Cecilie, Jensen, Tina Kold, Fernandez, Mariana F., Rosenmai, Anna Kjerstine, Taxvig, Camilla, Rodriguez-Carrillo, Andrea, Wielsøe, Maria, Long, Manhai, Olea, Nicolas, Antignac, Jean-Philippe, Hamers, Timo, Lamoree, Marja
• Format: Article
• Language: English
• Subjects: Biomarker; Ecology, environment; Effect-directed analysis; Environmental Exposure; Environmental Pollutants - toxicity; Human diseases; Human health; Humans; In vitro assays; Life Sciences; Mixtures; Receptors, Cytoplasmic and Nuclear
• ISSN: 0160-4120; 1873-6750
• DOI: 10.1016/j.envint.2020.106191

•Human exposure to chemical cocktails demands new technologies to assess this combined exposure.•Receptor-based in vitro assays can be used as biomarkers of effect in human tissue.•In vitro biomarkers of effect take mixture effects of chemicals into account.•AhR, ER and AR activities have been linked to various disease outcomes in humans.•The potential of true effect-directed analysis on human tissues remains to be explored. 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 c