EuroMix project deliverables
The page lists 44 deliverables related to the research project "EuroMix".
List of Deliverables
| title and desprition | type | last update |
|---|---|---|
Specific recommendations regarding implementation of a mechanism-based test strategy for liver, developmental and endocrine for OECDThe EuroMix has defined liver, endocrine and developmental immuno toxicological endpoints as test cases and consequently experiments will be performed throughout the whole project addressing these endpoints. Horizontal activity leaders (KI, ICL) will collect information from other WPs and will summarize the findings in line with OECD discussions and test regulation. They will pursued the new guidance developed in task 8.2 on how new mechanism-based testing should be addressed in existing OECD, EFSA, ECHA and/or ECVAM guidelines or proposals to adapt this existing test guidance. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report on the comparative outcome of using new mechanism-based testing and consequences for animal testing and uncertainties in risk assessmentKI will make a proposal of the relevant elements to integrate in a tiered assessment strategy (milestone 8.3). The web-based EuroMix tool developed in WP6 will be used for test runs of case studies (identified in WP2-WP4) to test the proposed criteria. The extensive toxicological testing from a wide range of techniques and experimental models, including e.g. in-silico, in-vitro, in-vivo, and PB-PK/D experiments, conducted by EuroMix will provide an excellent basis to evaluate the outcome of proposed approach as compared with current methods/models for risk assessment, and the pro’s and con’s of different approaches will be discussed. The results will be described in deliverable 8.5 (M45) and will be used in WP9 and WP10. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report of WHO consultation workshop and feasibility studyWHO, with help of RIVM, in its capacity of WHO/FAO collaborating centre for food safety, and Ugent, having global experience based on the EU funded project Veg-i-trade, will define achievable goals for higher tier assessment at the global level. Data at WHO is structured differently from EFSA and different from the USA. WHO and EFSA have made a conversion table for GEMS FOOD and FoodEx and the usability of this table will be tested and when possible implemented in WP6. WHO, Ugent and RIVM will define a will provide instructions how exposure assessment as performed in WP5 can be reproduced in Brazil and Thailand. Brazil and Thailand have been added to the project as associated partners. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Minutes of meetings with External Advisory BoardThe coordinator will also organize three meetings with the External Advisory Board to ensure an optimal fine-tuning with the needs of international risk assessment and risk management institutes. The discussions will be summarised and recommendations will be given n deliverable 1.4. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific paper ready for submission describing the PB-PK/D model approachBiological materials (serum samples and/or leucocytes) from subjects with known exposure to the selected chemicals in the mixture (task 7.2) will be analysed for biomarkers of effects as selected based on the studies in WP3 and WP4 focussing on hepatic, developmental or endocrine endpoints. The exact identification of the biomarkers of effects need to await reporting of the results from the in vivo and in vitro study but might include clinical chemistry endpoints, RNA array profiling data, DNA and/or protein adducts or other biochemical markers associated with the effects observed. Based on the biomarkers selected appropriate laboratories performing these analyses will be selected based on experiences and methods available. Inter-individual variability in the biomarkers of effect will be studied. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific article ready for publication describing the method to identify mixturesANSES, in cooperation with RIVM, will define exposure scenarios. The scenarios will address the cumulative assessment groups defined by EFSA and based on data organized in task 5.1. ANSES, RIVM, CZU, MATIS, Ugent, HSE, NIJZ, URV, BPI and Ministry of Health of the Republic Cyprus will divide the exposure scenarios and chemicals of interest. Exposure calculations will be performed using probabilistic methods already implemented in the ACROPOLIS-IT tool, which is part of the EuroMix web-based model toolbox. Depending on the nature of the risk (acute or chronic), exposure will be estimated at the person-day or person level, respectively. Acute exposure will be calculated by Monte Carlo integration of consumption and concentration distributions. Chronic exposure will be calculated using the Logistic Normal-Normal (LNN) model. NIJZ, BPI and Ministry of Health of the Republic Cyprus will search for processing factors in the open literature and/or Draft Assessment Reports. The calculations will account for processing effects and unit variability as far as practically possible. This will result a scientific article ready for publication (deliverable 5.1). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report with recommendation for OECD and other international organisationsBased on the tiered testing strategy proposed by the WHO and the integration of the test results of WP2-4 and WP6 for risk assessment purposes, KI and UoO will set criteria and framework for proceeding to higher-tier testing strategy and will provide guidance on how to use the tiered test and risk assessment strategy (deliverable 8.3, M45). Early communication form Ugent on the attitudes of stakeholders is relevant (milestone 8.2). KI will propose test recommendations (deliverable 8.4, M45) on how new mechanism-based testing should be addressed in relation to existing OECD, EFSA, ECHA and/or ECVAM guidelines (see also task 9.2). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific article describing the PB-PK model for combined exposuresINERIS will develop specific metabolic pathways models for the substances to be studied and will couple them to the PB-PK model of URV. INRA will perform dedicated in-vitro experiments with primary hepatocytes to obtain values for metabolic rate constants (Vmax, Km, etc.) for the substances studied. Other parameter values will be obtained from the literature or QSAR modelling. For mechanistic (systems biology) PD modelling on the basis of specific MoAs for endocrine descriptors and hepatotoxicity, the two models recently published by INERIS on steroidogenesis and nrf2/GSH pathway will be adapted and coupled to the PB-PK + metabolism model just described. The PB-PK-PD models developed will be first aimed to guide in-vivo experiments on selected endpoints and groups of compounds. They will also be used for IVIVE, prediction of cumulative exposures (WP3), potential biomarkers levels in humans (WP7) and will be made available to the toolbox of WP6. (M24). The PB-PK/D modelling exercise and results will be described in deliverable 4.2. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific paper ready for submission describing biomarker studyThe ongoing Human Biomonitoring project, which is a part of the Norwegian Mother and Child Cohort, at NIPH will be used to collect serum (2000 µl), lymphocytes (100 µl) and urine (5 ml) from adults, 70 males and 70 females (in total 140 participants). Serum and urine samples will be used to assess cumulative and aggregated exposure to the selected chemicals in the mixture. A 48 hours diary based on weighing of the consumed food will be performed prior to sample collection, and used together with concentration data in foods for the estimation of exposure. Analytical methods for 3 metabolites of interest in serum and/or urine will be developed to estimate the level of exposure (NIPH). Variability will be studied and estimated exposure will be compared with the levels of biomarkers for exposure in urine or serum. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Final version of EuroMix model toolbox including hazard and PB-PK/D modelsThis task will implement in the probabilistic setting of the EuroMix tool a) PB-PK models to convert external exposure to organ-level exposure; b) extrapolation methods from in-vitro to in-vivo exposure (QIVIVE module). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Other | 2020-04-22 |
PB-PK/D modelling for the index compound of the chosen endpointsINERIS, URV and INRA will take the lead in PB-PK/D modelling for both single chemicals and combined exposures. The generic PB-PK/D model already developed at URV will be extended to include inhalation and dermal exposure components. The PB-PK/D models for the index compounds will be described in deliverable 4.1. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Other | 2020-04-22 |
Minutes of meetings with Scientific Advisory BoardThe coordinator will implement an effective innovation management strategy. RIVM will organize three meetings with the scientific advisory board. The discussions and recommendations of these meetings will be summarised in deliverable 1.3. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific article ready for submission describing the results of the in vitro testing of mixturesThe most pertinent in vitro tests as selected in task 3.1 will be used to test a broader range of chemicals selected within WP2 and WP5. Mixtures of chemicals that are listed in CAG as established by the PPR panel of EFSA for pesticides will be chosen, as well as mixtures of pesticides and non-pesticides, and these will be tested with the battery of in vitro assays as well as with the CAG-specific PCR arrays. The dose-response effects of the individual chemicals (similar and dissimilar MoA) will be compared to those of the mixtures in order to determine whether the mixtures are behaving according to the CA or IA model (WP4). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report on stakeholder workshop 1The project will only be truly successful if its outcomes are widely used by relevant stakeholders, and survive beyond the end of the project. Therefore, it is important that the project will deliver results that meet the needs of the stakeholders, and that stakeholders are aware of it. This necessitates continued stakeholder involvement throughout the project. To accomplish this a number of stakeholder activities are planned: Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report describing the methodology and results of the refine and retain approachThe combined exposure levels as reported in task 5.2 for the cumulative assessment groups set by EFSA will be used as a starting point. This includes a large number of chemical and a number of chemicals will hardly contribute to the risk. WP3 and WP4 will perform the mixture experiments resulting in more refined information about relative potency factors, dose-addition, mixture endpoints, and information about inclusion or exclusion of chemical in the cumulative assessment groups. Cumulative exposure scenarios will be developed starting from worst-case scenario including all chemicals and working towards including more refined information and addressing only the chemicals significantly contributing to the exposure levels defined in task 5.3. DEFRA will write a report describing the results and how to perform the refine and retain approach. This corresponds to deliverable D5.5, which will be ready in M44. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Demonstration tool cumulative exposure assessmentANSES, in cooperation with RIVM, will define exposure scenarios. The scenarios will address the cumulative assessment groups defined by EFSA and based on data organized in task 5.1. ANSES, RIVM, CZU, MATIS, Ugent, HSE, NIJZ, URV, BPI and Ministry of Health of the Republic Cyprus will divide the exposure scenarios and chemicals of interest. Exposure calculations will be performed using probabilistic methods already implemented in the ACROPOLIS-IT tool, which is part of the EuroMix web-based model toolbox. Depending on the nature of the risk (acute or chronic), exposure will be estimated at the person-day or person level, respectively. Acute exposure will be calculated by Monte Carlo integration of consumption and concentration distributions. Chronic exposure will be calculated using the Logistic Normal-Normal (LNN) model. NIJZ, BPI and Ministry of Health of the Republic Cyprus will search for processing factors in the open literature and/or Draft Assessment Reports. The calculations will account for processing effects and unit variability as far as practically possible. This will result a demonstration tool (deliverable 5.2). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Demonstrators, pilots, prototypes | 2020-04-22 |
Scientific paper ready for submission on models and software for QIVIVE and AOPA functional design will be prepared by INERIS, in collaboration with URV, RIVM, DLO-R and DLO-B, with advice from EPA and ICL (Milestone 6.3, M24). Models to calculate benchmark doses (or similar hazard characterisation measures) for chemicals and/or mixtures of chemicals from omics and/or bioassay data obtained from in-vitro studies (from WP 4), calibrated on similar measurements in animal studies. A method to select predictive gene or metabolite sets will be implemented. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific article ready for submission describing the in vitro testing strategy for immune toxicityThe most pertinent in vitro tests as selected in task 3.1 will be used to test a broader range of chemicals selected within WP2 and WP5. . Mixtures of chemicals that are listed in CAG as established by the PPR panel of EFSA for pesticides will be chosen, as well as mixtures of pesticides and non-pesticides, and these will be tested with the battery of in vitro assays as well as with the CAG-specific PCR arrays. The dose-response effects of the individual chemicals (similar and dissimilar MoA) will be compared to those of the mixtures in order to determine whether the mixtures are behaving according to the CA or IA model (WP4). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Validation of the aggregated model and comparison with USA softwareThe modelling approach for aggregate exposure implemented in WP 6 will be validated by ANSES and DLO-B. Validation of the software for aggregate exposure assessment is important. The new model for aggregate exposure assessment will be validated in two different ways. First, unit tests will be written to assure the proper working of the code at a low level. These unit tests will simulate data with known outcomes, and check that the software performs adequately. DLO-B will set up simulation studies and will compare model outcomes with the true values behind the simulated data. Secondly, the new software is compared to the standard program for the exposure assessment of pesticides in the US by the EPA, which is DEEM-SHEDS. For the aggregated models ANSES, with the help of DLO-B, will compare the EuroMix model with the model used in the EPA (e.g. SHEDS-Multimedia). ANSES and DLO-B will write a validation report (D7.1, M36) Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific article ready for submission describing the case study for aggregated exposure assessmentETHZ and ANSES will make a database with available data of concentrations in consumer products or non-dietary matrix for the selected endpoints (liver, development and endocrine). The level of aggregated exposure will also be determined by individual habits. ETHZ will overview the availability and usability of that data. Priority will be given to substances in the selected mixtures of task 5.3 and to chemicals mainly present in the diet. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report on stakeholder workshop 2The project will only be truly successful if its outcomes are widely used by relevant stakeholders, and survive beyond the end of the project. Therefore, it is important that the project will deliver results that meet the needs of the stakeholders, and that stakeholders are aware of it. This necessitates continued stakeholder involvement throughout the project. To accomplish this a number of stakeholder activities are planned: Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Guidance on the use of the new strategy for tiered testing and assessmentKI will perform a literature review of the currently used and proposed approaches to evidence- and risk-based health risk assessment of chemical mixtures. Part of the review will be addressing this framework will be tested for Risk Assessment and Management of Combined Exposure to Multiple Chemicals in Drinking Water and Source Water using available measurement data of relevant substances in tap water (KI and RIVM). CZU, ANSES, URV and MATIS, having access to total diet studies from several countries, will perform an exposure case study in addition to include data from a total diet study (TDS) based on the experience of the EU project Total Diet Study Exposure. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Plan for the dissemination and exploitation of the results from EuroMixThe Plan defines a clear set of actions for the 4 years including purpose, target group, method, vehicle, timing and success criteria. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific article ready for publication balancing risk of mixtures against benefitsPositive health effects of food will be evaluated by using the Qalibra tool. The BRAFO test strategy for risk-benefit analyses will be applied for balancing the risk of mixtures against beneficial components in the same food. MATIS, UGent, URV and DEFRA will address this issue in a case study to be selected one year into the project. The selected case study will be one of the following: 1) the benefit of consuming fruits and vegetables vs. the combined risk of pesticides present in the same food stuffs on the effects of concern studied in WP3 and 4. The case study will be reported in a draft scientific paper as deliverable 8.2 (M36). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Proceedings and training material from first training session for stakeholdersTo maximise implementation of the new risk assessment strategies developed in the project, training will be given for the stakeholders who will use the new integrated models. The aim of the training sessions is that the stakeholders will gain understanding of the scientific basis behind the new risk assessment strategies, be able to use the developed tools and to interpret and assess the output as well as implement the strategies in their own context. The training will be developed with input from the Scientific Advisory Board and from user groups from industry and authorities, which will test the tools. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Demonstrators, pilots, prototypes | 2020-04-22 |
Scientific article ready for publication describing the in vivo studiesFor the selected toxicological apical endpoints (liver, developmental, endocrine and immuno toxicity) animal experiments will be designed to validate the molecular signatures against toxicological findings in animals, and to verify the CAGs created on the basis of the in-vitro models laid out in WP3 and PB-PK/D models (Task 4.2.). Selection of mixtures will be done in close cooperation with WP3and with WP7, which will validate the overall approach of the EuroMix test strategy. The index compounds will be tested in a benchmark design, with a dose-range, covering both human exposure levels and effect levels (e.g. between the NOAEL and the LOAEL). Other compounds included in the same CAG blased on toxicological consideration will be tested alone or in combination and the dose response curves will be compared with those expected based on the modelling (BMD and/or PB-PK-PD). The choice of the CAG compounds to be tested will be based on several considerations: e.g.: mode of action, target organ/system effect, pesticides contributing most to exposure (as identified in WP5), non-pesticide chemicals that appear to provide the most relevant exposure levels for humans, and other chemicals that may prove useful to serve in a case study for proof-of-principle. Relevant organs and tissues of the treated animals will be examined for morphological, histological, and molecular alterations, as suggested by the in-vitro studies conducted under WP3. The outcome of this analysis will be compared with the predictions made based on the in-vitro studies conducted under WP3. The design of the animal studies will be tailored on the question to be asked, taking advantage of the existing OECD Guidelines for a 28-day study (OECD 407) for liver toxicity, for developmental toxicity (OECD 414), and endocrine and (limited) immuno toxicity (Extended One Generation Reproduction Toxicity, OECD 442). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific paper ready for submission on the EuroMix toolbox and softwareDLO-B, together with ICL, ANSES, DEFRA, URV and others, will optimize and implement models for compound prioritization based on Margin of Exposure (MoE) in a ‘refine and retain’ setting. This will provide a practical implementation of the RISK21 matrix approach in a fully probabilistic setting. The QALIBRA model will be linked into the EuroMix tool, in collaboration between DLO-B and DEFRA. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
The use of QSAR and TTC approaches to prioritise chemicals for mixturesThe predictive value of individual QSAR models has been discussed in several publications. It has been shown repeatedly that appropriate combined use of QSAR models in an Integrated Testing Strategy, or in a statistical (Bayesian) Weight of Evidence procedure allows the user to select substances for which the prediction of toxicity has sufficiently high reliability. On the basis of the experiences obtained in the preceding tasks, Fera and RIVM, with support of all other WP1 partners, will set up a strategy for the integrated use of QSAR and TTC approaches in the testing of mixtures. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Scientific article ready for submission describing the in vitro testing strategy for developmental/endocrine toxicityThe most pertinent in vitro tests as selected in task 3.1 will be used to test a broader range of chemicals selected within WP2 and WP5. . Mixtures of chemicals that are listed in CAG as established by the PPR panel of EFSA for pesticides will be chosen, as well as mixtures of pesticides and non-pesticides, and these will be tested with the battery of in vitro assays as well as with the CAG-specific PCR arrays. The dose-response effects of the individual chemicals (similar and dissimilar MoA) will be compared to those of the mixtures in order to determine whether the mixtures are behaving according to the CA or IA model (WP4). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Minutes of meetings discussing harmonisation between Europe, EPA and WHOThe EuroMix has defined liver, endocrine and developmental immuno toxicological endpoints as test cases and consequently experiments will be performed throughout the whole project addressing these endpoints. Horizontal activity leaders (KI, ICL) will collect information from other WPs and will summarize the findings in line with OECD discussions and test regulation. They will pursued the new guidance developed in task 8.2 on how new mechanism-based testing should be addressed in existing OECD, EFSA, ECHA and/or ECVAM guidelines or proposals to adapt this existing test guidance. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Proceedings and training material from second training session for stakeholdersTo maximise implementation of the new risk assessment strategies developed in the project, training will be given for the stakeholders who will use the new integrated models. The aim of the training sessions is that the stakeholders will gain understanding of the scientific basis behind the new risk assessment strategies, be able to use the developed tools and to interpret and assess the output as well as implement the strategies in their own context. The training will be developed with input from the Scientific Advisory Board and from user groups from industry and authorities, which will test the tools. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Demonstrators, pilots, prototypes | 2020-04-22 |
Scientific article rady for submission on cumulative assessment of mixtures of several chemical classesANSES, in cooperation with RIVM, will define exposure scenarios. The scenarios will address the cumulative assessment groups defined by EFSA and based on data organized in task 5.1. ANSES, RIVM, CZU, MATIS, Ugent, HSE, NIJZ, URV, BPI and Ministry of Health of the Republic Cyprus will divide the exposure scenarios and chemicals of interest. Exposure calculations will be performed using probabilistic methods already implemented in the ACROPOLIS-IT tool, which is part of the EuroMix web-based model toolbox. Depending on the nature of the risk (acute or chronic), exposure will be estimated at the person-day or person level, respectively. Acute exposure will be calculated by Monte Carlo integration of consumption and concentration distributions. Chronic exposure will be calculated using the Logistic Normal-Normal (LNN) model. NIJZ, BPI and Ministry of Health of the Republic Cyprus will search for processing factors in the open literature and/or Draft Assessment Reports. The calculations will account for processing effects and unit variability as far as practically possible. This will result in a scientific article ready for submission on cumulative assessment of mixtures of several chemical classes (deliverable 5.3). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report on the needs and attitudes of stakeholders to the test strategyThe project will identify and interview international consumer groups, non-governmental organizations, retailers, regulators, quality managers of multiples food suppliers and consumers regarding their needs and resources in terms of performing risk assessment. Besides assessing potential opportunities, threats, strength and weaknesses from the stakeholders’ perspective, the level of understanding and acceptability of different developed concepts and perceived information needs will also be explored. The current task includes drafting of the study protocol and interview guides, execution and transcription of the interviews. To identify and select appropriate stakeholders, UGent will rely on FOOD2Know, a food research platform with multiple stakeholders and various ongoing international partnerships with stakeholders in food safety around the world in particular. The results will be reported in draft scientific publications ready for submission as deliverable 8.1. (M24). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Position paper on gaps to be filled in existing legislationBfR and BPI will prepare an overview of how mixture testing and higher tier modelling are addressed in current regulatory toxicology and how it should be addressed ideally in the future. This will be complementary to task 8.2. The focus will be on general aspects related to EFSA and DG SANCO discussion, the need to reduce animal testing and to specific aspects related to the chemicals selected in the EuroMix. BfR, BPI and ICL will identify potential gaps in legislation and will provide recommendations on how the EuroMix test approaches and assessment strategies including non-testing approaches should be placed in the context of OECD, EFSA, ECHA and ECVAM guidelines or guidance documents. They will produce a position paper (Deliverable 9.1) that can be discussed with the DG SANCO, DG ENV, EFSA and ECHA and can be used in the stakeholder conference (see WP10). D9.1 will be ready in M18. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Demonstration prototype of EuroMix model toolbox (module priority setting).In an early stage, ANSES will provide a method for identification of major mixtures in terms of exposure, based on the model developed in the PERICLES programme (Béchaux et al. 2013). DLO-B with the help of ANSES will implement a module to select the appropriate combinations of chemicals for mixture experiments of combined exposure to multiple food-related toxic substances, based on exposure patterns, possibly weighted by relative potency factors (Milestone 6.1, M6). The chemicals contributing most to the exposure will be identified, and will be the basis for mixture testing in WP3 and WP4. These models will be tested using data gathered in Task 5.1 (M7-9). DLO-B will provide a demonstration prototype of the EuroMix model toolbox to integrate exposure assessment of selected and unselected chemicals based on a ‘Retain and refine’ concept (Deliverable 6.1, M18). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Demonstrators, pilots, prototypes | 2020-04-22 |
Informative posters and booklets/brochures•Templates for presentations; Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Websites, patent fillings, videos etc. | 2020-04-22 |
CAG-specific PCR arraysTranscriptomic analysis will be conducted in order to obtain information on the level of gene regulation in the different cellular models. Rat/human primary hepatocytes (INRA) and HepaRG cells/HepG2 cells (liver; BfR, INRA, RIKILT), MCF7 breast cells (endocrine effects; RIKILT), zebrafish embryos/stem cells (development; RIVM/KI) and JURKAT cells (immunotox; RIKILT) will be treated with the training compounds, total RNA will be extracted from the cells and subjected to hybridisation with whole genome arrays. The array data of all partners will be imported into a central database managed by DLO-B and (upon publication of the data) submitted to the ArrayExpress Database of EMBL-EBI (see also WP6 Task 6.3). Bioinformatics will be employed by using software tools to generate molecular networks based on the microarray data yielding molecular signalling, toxicity and/or metabolic pathways being deregulated (e. g. Ingenuity Pathway Analysis, BfR; RIKILT). Within this analysis, we will also refer to a number of databases of expression profiles of toxicants that are currently becoming available. These are, e.g., the “Connectivity Mapâ€, which is a resource of 6100 arrays with expression profiles of more than 1300 compounds mainly used for exposure of MCF7 cells and which has recently been expanded and is now containing data of more than 5500 perturbations and 18 cell lines (http://lincscloud.org/). Other relevant databases considered are “Drugmatrix†(https://ntp.niehs.nih.gov/drugmatrix/index.html), “Dixa†(http://wwwdev.ebi.ac.uk/fg/dixa/index.html), and “TG Gates†(http://toxico.nibio.go.jp/open-tggates/english/search.html. Specific target areas of the embryo (UMIL) will be examined for specific gene expression related to retinoic acid metabolism, that is involved in malformations. Based on the bio-informatic analysis, similar and dissimilar MoA will be defined among the tested compounds crucial for grouping these compounds into CAGs. The results of the transcriptomic analysis will also be used for model building within WP6 (Task 6.4). The molecular signatures obtained by the transcriptomic approach, as well as the information generated by the models developed in WP6, will be used for the selection of sets of commonly modulated genes in order to develop CAG-specific PCR arrays as a deliverable (D3.1, M24), that will subsequently be used for testing and grouping of additional chemicals and for mixtures (see below). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Other | 2020-04-22 |
Pan for managing and releasing open dataThe coordinator will made a plan for the management of open data before month 6 and will discuss the plan during the second consortium meeting. The plan, deliverable 1.2, will be submitted to DG Research according to the new requirements in Horizon2020 in month 6. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Open Research Data Pilot | 2020-04-22 |
Report usefulness of the TTC concept for risk assessment of mixturesThis task, to be performed by ICL, BPI, NIPH and HSE aims to use the TTC concept for excluding chemicals from the list of substances initially identified in Task 2.1 (and further adjusted by the in-silico analyses of Task 2.2). More generally, the outcome of this task will also be used to assess the applicability of the TTC approach in a tiered testing strategy for mixtures (in Task 2.4 and WP8). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Gender PlanRIVM is responsible for the implementation of a gender management strategy and promote gender equality. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report describing cumulative assessment groups for a broad range of chemicals, based on information extracted from (literature) databasesThis task will be performed by RIKILT, BPI, SGL, UMIL and KI provide a list of chemicals that serve as a basis for the other tasks in this WP (Milestone 2.1, M4). This list will not only contain pesticides that are classified in cumulative assessment groups as recently established by EFSA’s PPR panel. EuroMix partners UMIL, ANSES and RIVM have provided EFSA with an approach for grouping pesticides and the basic toxicological data required for this. In this task, a similar strategy will be set up and used for the grouping of non-pesticide chemicals. The following chemical classes will be considered: Environmental pollutants (e.g. dioxins, PAHs), food contaminants (e.g. mycotoxins), chemical migrants from food package materials (NIAS), known and suspected endocrine active chemicals, biocides, and bioactive alkaloids (e.g. pyrrolizidine alkaloids). To that end, publicly available data sources and (literature) databases, such as e-ChemPortal, GEMS/Food Program, and EFSA databases, will be exploited. The final list of this task will consist of chemicals with known and suspected toxicity with focus on the endpoints selected for the EuroMix project, i.e. liver toxicity, developmental toxicity, endocrine effects and immunotoxicity. The literature review and database searches will result in in a report (Deliverable 2.1, M18). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Report on the use of in-silico methods for the prioritisation of mixtures thereofIn this Task DEFRA, RIVM and UMIL will explore the use of in-silico approaches for the identification/prioritisation of compounds and mixtures in relation to assessment of effects associated with the selected endpoints. In-silico methods will include (Q)SARs, toxicity expert systems, and read-across approaches. DEFRA scientists participating in this task have longstanding expertise in data mining and in-silico modelling. RIVM is project management group member OECD QSAR ToolBox and advisory board member for the Danish (Q)SAR Database. Furthermore, UMIL has expertise with in-silico tools/computational models particularly for Endocrine Active Substances. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |
Website for EuroMix projectMATIS will develop the project website: development of a multifaceted website with; 1) A public platform with general information about the project’s approach, objectives, results, and methodology 2) A private platform for the partners, where the relevant project documents, drafts, etc. can be presented for consultation and discussion 3) The project web site will be used to support the community of users of the final software for exposure-driven mixture testing e.g. with a glossary of list of terms used on the website and in the tool, explaining the general framework. Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Websites, patent fillings, videos etc. | 2020-04-22 |
Scientific article ready for submission describing the in vitro testing strategy for liver toxicityThe most pertinent in vitro tests as selected in task 3.1 will be used to test a broader range of chemicals selected within WP2 and WP5. . Mixtures of chemicals that are listed in CAG as established by the PPR panel of EFSA for pesticides will be chosen, as well as mixtures of pesticides and non-pesticides, and these will be tested with the battery of in vitro assays as well as with the CAG-specific PCR arrays. The dose-response effects of the individual chemicals (similar and dissimilar MoA) will be compared to those of the mixtures in order to determine whether the mixtures are behaving according to the CA or IA model (WP4). Programme: H2020-EU.3.2. - Topic(s): SFS-12-2014 |
Documents, reports | 2020-04-22 |