RT Journal Article T1 Receptor-based in vitro activities to assess human exposure to chemical mixtures and related health impacts. A1 Vinggaard, Anne Marie A1 Bonefeld-Jørgensen, Eva Cecilie A1 Jensen, Tina Kold A1 Fernandez, Mariana F A1 Rosenmai, Anna Kjerstine A1 Taxvig, Camilla A1 Rodriguez-Carrillo, Andrea A1 Wielsøe, Maria A1 Long, Manhai A1 Olea, Nicolas A1 Antignac, Jean-Philippe A1 Hamers, Timo A1 Lamoree, Marja K1 Biomarker K1 Effect-directed analysis K1 Human diseases K1 Human health K1 In vitro assays K1 Mixtures AB 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. YR 2020 FD 2020-10-14 LK http://hdl.handle.net/10668/16439 UL http://hdl.handle.net/10668/16439 LA en DS RISalud RD Apr 8, 2025