During the first 3 years 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 have been performed and a publication is submitted.
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. Analytical determination of chemicals in the fractions has been performed and confirmation of activities is being planned.
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 have been tested in seven bioassays, selected and based on phase I results and chemical profiling of pooled samples have been performed. At the moment we are doing statistical analysis of the bioassay outcomes and the chemical profiling data in relation to adverse health outcomes.
On the theoretical side, we have designed a prototype of a 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 planned 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 makes progress with most deliverables and milestones reached as planned, although a few deliverables are delayed because of delay of the complex experimental studies.
