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. 2022 Oct 11;19(20):12990.
doi: 10.3390/ijerph192012990.

Mixture Risk Assessment of Complex Real-Life Mixtures-The PANORAMIX Project

Beate I Escher  1   2 , Marja Lamoree  3 , Jean-Philippe Antignac  4 , Martin Scholze  5 , Matthias Herzler  6 , Timo Hamers  3 , Tina Kold Jensen  7 , Marc Audebert  8   9 , Francois Busquet  10 , Dieter Maier  11 , Michael Oelgeschläger  6 , Maria João Valente  12 , Henriette Boye  13 , Sebastian Schmeisser  6 , Gaud Dervilly  4 , Matteo Piumatti  10 , Soléne Motteau  4 , Maria König  1   2 , Kostja Renko  6 , Maria Margalef  3 , Ronan Cariou  4 , Yanying Ma  12 , Andreas Frederik Treschow  12 , Andreas Kortenkamp  5 , Anne Marie Vinggaard  12
Affiliations

Mixture Risk Assessment of Complex Real-Life Mixtures-The PANORAMIX Project

Beate I Escher et al. Int J Environ Res Public Health. .

Abstract

Humans are involuntarily exposed to hundreds of chemicals that either contaminate our environment and food or are added intentionally to our daily products. These complex mixtures of chemicals may pose a risk to human health. One of the goals of the European Union's Green Deal and zero-pollution ambition for a toxic-free environment is to tackle the existent gaps in chemical mixture risk assessment by providing scientific grounds that support the implementation of adequate regulatory measures within the EU. We suggest dealing with this challenge by: (1) characterising 'real-life' chemical mixtures and determining to what extent they are transferred from the environment to humans via food and water, and from the mother to the foetus; (2) establishing a high-throughput whole-mixture-based in vitro strategy for screening of real-life complex mixtures of organic chemicals extracted from humans using integrated chemical profiling (suspect screening) together with effect-directed analysis; (3) evaluating which human blood levels of chemical mixtures might be of concern for children's development; and (4) developing a web-based, ready-to-use interface that integrates hazard and exposure data to enable component-based mixture risk estimation. These concepts form the basis of the Green Deal project PANORAMIX, whose ultimate goal is to progress mixture risk assessment of chemicals.

Keywords: PANORAMIX; developmental neurotoxicity; effect-based trigger values; effect-directed analysis; mixture risk assessment; new methodological approaches; real-life mixtures; reproductive toxicity.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the writing of the manuscript; or in the decision to publish the results. The companies had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Current approach on chemical risk assessment and the challenge of mixture risk assessment addressed by PANORAMIX. The letters A–G refer to different compounds (modified from [2]).
Figure 2
Figure 2
Overview of Phases 1 and 2 of the workplan for whole mixture screening based on high-throughput in vitro new methodological approaches. Pooled blood/water/fish/food: samples from a large number of European countries or European individuals are pooled, and thereafter the chemicals are extracted from the pools. ACHE: acetylcholinesterase; TPO: thyroid peroxidase; TTR: transthyretin; TBG: thyroid hormone binding globulin; GH3-TRE-luc: reporter gene bioassay that can measure thyroid hormone receptor mediated activity; ER: estrogen receptor; AR: androgen receptor; hIPSC: human-induced pluripotent stem cells; Nrf2: nuclear factor erythroid 2–related factor 2; AhR: arylhydrocarbon receptor; PPAR: peroxisome proliferator-activated receptor.
Figure 3
Figure 3
Schematic representation of the workflow entailed by the effect-directed analysis approach. EDA: effect-directed analysis; HRMS: high resolution mass spectrometry; LC—liquid chromatography; SPE: solid-phase extraction.
Figure 4
Figure 4
Illustration of the approach for the identification of a potential correlation between whole mixture-based in vitro outcomes and identified chemical mixture drivers in human cord blood samples and reproductive and neuropsychological health outcomes in children. ADHD: attention deficit hyperactivity disorder.
See this image and copyright information in PMC

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