Periodic Reporting for period 1 - PANORAMIX (Providing risk assessments of complex real-life mixtures for the protection of Europe?s citizens and the environment)
Période du rapport: 2021-11-01 au 2023-04-30
Humans are exposed to a large number of different chemicals on a daily basis in the form of chemical mixtures from food, consumer products and the environment, some of which will show mixture effects. These complex chemical mixtures may pose a risk to human health, but chemical legislation is still not implemented to take this issue into account. PANORAMIX is a public-private consortium formed in line with the EU’s Green Deal and zero-pollution ambition for a toxic-free environment, whose ultimate goal is to tackle the existent gaps in chemical mixture risk assessment, by providing scientific grounds that support the implementation of adequate regulatory measures. Thus, PANORAMIX aims to contribute to close critical gaps in the mixture risk assessment of chemicals throughout the environment-food-human continuum.
The objectives of PANORAMIX are:
• to characterize chemical mixtures and to what extent they are transferred from the environment to humans via food and water, and from the mother to her foetus
• to establish a strategy for screening of real-life complex mixtures of chemicals extracted from human blood, food and environmental samples based on whole-mixture assessment in bioassays
• to identify mixture effects and their drivers in humans using integrated chemical profiling together with effects obtained in bioassays (i.e. effect-directed analysis)
• to evaluate which human blood levels of chemical mixtures might be of concern for reproductive and neuropsychological health in children
• to develop a pragmatic web-based interface to enable component-based mixture risk estimation
The objectives of PANORAMIX are:
• to characterize chemical mixtures and to what extent they are transferred from the environment to humans via food and water, and from the mother to her foetus
• to establish a strategy for screening of real-life complex mixtures of chemicals extracted from human blood, food and environmental samples based on whole-mixture assessment in bioassays
• to identify mixture effects and their drivers in humans using integrated chemical profiling together with effects obtained in bioassays (i.e. effect-directed analysis)
• to evaluate which human blood levels of chemical mixtures might be of concern for reproductive and neuropsychological health in children
• to develop a pragmatic web-based interface to enable component-based mixture risk estimation
During the first 1½ year of PANORAMIX, planning and execution of several experimental and theoretical activities have been performed. In phase I of the project, we investigate how many and which chemicals drive the mixture effects in human, environmental, water and food samples and may pose a threat to human health. Partners have been collecting water, fish, milk, and human blood samples from a diverse range of ‘suppliers’ from their country and transferred to the lab in charge of pooling and extracting chemicals from the samples. Our intention was to get close to ‘an average European chemical mixture’ for most matrices. These 16 extracts of ‘real-life’ mixtures have been tested in 20 bioassays in five labs. With this work on enriched extracts across the environment-human continuum, we have observed effects representing a high diversity of biological endpoints. Chemical identification of the extracts is in progress.
To determine the chemical drivers of the mixture effects, we need an initial filter to focus on chemicals of potential concern. Therefore, we are combining bioassay effects of extracts with chemical identification (so-called effect-directed analysis) with the goal of identifying chemical mixture drivers in the phase I mixtures. Water, food and human milk and blood extracts have been fractionated and each fraction tested in five selected bioassays. Currently, analytical determination of chemicals in the fractions is in progress.
In phase II of the project, we focus on children’s health by investigating associations between chemicals detected in human cord blood and reproductive and neuropsychological health in the children. We have selected 750 human cord blood samples from children in the Odense Child Cohort with relevant health information. The cord blood samples were selected based on available information on biomarkers for reproductive health and neuropsychological development (IQ, language development, ADHD) in the children. The chemical mixtures in these blood samples will be tested in seven bioassays, selected and based on phase I results.
On the theoretical side, we have started designing the user interface for calculation of mixture effects - Chemical Mixture Calculator 2.0. The intention is to develop a platform that allows for an initial, preliminary assessment of risk to a specific chemical mixture. We prioritize to have data on a large number of chemicals included in the system and to base the calculation of risk quotients on in vitro data linked to adverse outcomes and predicted human exposure data.
Moreover, we have started planning for four theoretical case studies (two on neurotoxicity and two on reproductive toxicity) on mixture risk assessment. The aim is to evaluate current safety margins and to provide input for the discussion of applying a mixture allocation factor in chemical risk assessment.
The project is progressing as expected and according to the deadlines with 19 submitted deliverables submitted and all milestones achieved.
To determine the chemical drivers of the mixture effects, we need an initial filter to focus on chemicals of potential concern. Therefore, we are combining bioassay effects of extracts with chemical identification (so-called effect-directed analysis) with the goal of identifying chemical mixture drivers in the phase I mixtures. Water, food and human milk and blood extracts have been fractionated and each fraction tested in five selected bioassays. Currently, analytical determination of chemicals in the fractions is in progress.
In phase II of the project, we focus on children’s health by investigating associations between chemicals detected in human cord blood and reproductive and neuropsychological health in the children. We have selected 750 human cord blood samples from children in the Odense Child Cohort with relevant health information. The cord blood samples were selected based on available information on biomarkers for reproductive health and neuropsychological development (IQ, language development, ADHD) in the children. The chemical mixtures in these blood samples will be tested in seven bioassays, selected and based on phase I results.
On the theoretical side, we have started designing the user interface for calculation of mixture effects - Chemical Mixture Calculator 2.0. The intention is to develop a platform that allows for an initial, preliminary assessment of risk to a specific chemical mixture. We prioritize to have data on a large number of chemicals included in the system and to base the calculation of risk quotients on in vitro data linked to adverse outcomes and predicted human exposure data.
Moreover, we have started planning for four theoretical case studies (two on neurotoxicity and two on reproductive toxicity) on mixture risk assessment. The aim is to evaluate current safety margins and to provide input for the discussion of applying a mixture allocation factor in chemical risk assessment.
The project is progressing as expected and according to the deadlines with 19 submitted deliverables submitted and all milestones achieved.
We thrive to contribute to a scientific foundation for a sound chemical mixture risk assessment in the future that can be used by scientists, risk assessors, and regulators to implement mixture risk assessment across regulatory boundaries. The PANORAMIX outcomes will support the implementation of existing risk assessment and risk management approaches to reduce the most critical exposures, ultimately contributing to the EU’s zero-pollution ambition for a toxic free environment in the future.