European Monitoring of Congenital Anomalies: JRC-EUROCAT Report on Statistical Monitoring of Congenital Anomalies (2006 – 2015)

Worldwide, congenital anomalies are a leading cause of fetal death, infant mortality and morbidity in childhood. Of the 5.2 million births in the European Union (EU) each year, approximately 104,000 (2.5%) will be born with congenital anomalies. EUROCAT is a European network of population-based registries whose objectives are to provide essential epidemiologic information on congenital anomalies in Europe, to facilitate the early warning of new teratogenic exposures and to evaluate the effectiveness of primary prevention. Each year, EUROCAT performs statistical monitoring for both trends and clusters in time on 82 anomaly subgroups. Statistical monitoring relates to two of EUROCAT’s objectives: to provide essential epidemiologic information on congenital anomalies in Europe and to co-ordinate the detection of, and response to, clusters and early warning of teratogenic exposures. The results of the statistical monitoring are the basis for possible further investigations at the local registry level. In 2015 the Central Registry of EUROCAT was transferred from the University of Ulster to the JRC, and became part of the European Platform on Rare Diseases Registration. This is the first time the statistical monitoring has been performed by the JRC-EUROCAT Central registry. We report here the results of the monitoring performed on data for the birth years 2006-2015. Cases of congenital anomaly among livebirths, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly (TOPFA) at any gestation were included. We report both the statistical results and, where available, the outcome of preliminary investigations conducted by registries. For each anomaly, the trends in prevalence in each registry are shown and in addition the overall pan-European prevalence by single year of birth. Some congenital anomalies take a while to be reported; therefore the prevalence in the latest data is often underreported. Presenting the overall pan-European prevalence by single year allows for the influence of the most recent data (2015) to be evaluated.JRC.F.1-Health in Societ

EUROCAT - Surveillance of congenital anomalies in Europe: epidemiology of Down syndrome 1990 - 2014

Down syndrome accounts for 8% of all congenital anomalies. It is related to maternal age, which generally increased in Europe during the study period, with large differences in European regions. The analysis of data from the JRC-EUROCAT Central registry shows that the total prevalence of Down syndrome for 10 000 births increased from 16 in 1990 to 23 in 2015. The prenatal detection increased from 49% in 2005 to about 70 % in 2015, but territorial differences between countries and regions exist.JRC.F.1-Health in Societ

Surveillance of Cerebral Palsy in Europe: Development of the JRC-SCPE Central Database and Public Health Indicators

The Surveillance of Cerebral Palsy in Europe (SCPE) network was established in 1998, bringing together professionals and researchers working in population-based registries of children with Cerebral Palsy (CP) across Europe. The aims of the network are to collect population data on CP to inform and improve understanding of the disease, to raise standards of care for children with CP, disseminate knowledge for patients, health care professionals and key stakeholders, and to provide a framework for collaborative research. In 2016, to provide sustainability for this very important network, the SCPE Central Registry and European level coordination activities were transferred to the JRC and became part of the European Platform for Rare Diseases Registration. The SCPE Central Database is annually updated with new cases submitted by the SCPE Registries. In line with the mission of the JRC for providing evidence-based policy support, and in order to extend the use of the SCPE Central database to public health relevant outputs, the JRC-SCPE Central Registry launched the initiative of developing public health indicators. The public health indicators have been developed by based on collaboration between the JRC and the University Hospital of Toulouse. The input for the calculations of these indicators is based on data included in the standard SCPE dataset and collected annually by the registries in the JRC-SCPE Central Database. The current report describes the development of the JRC-SCPE Central Database after the transfer from the University of Grenoble, and the definition of a first set of key health indicators.JRC.F.1-Health in Societ

European Monitoring of Congenital Anomalies: JRC-EUROCAT Report on Statistical Monitoring of Congenital Anomalies (2008 - 2017)

Worldwide, congenital anomalies are a leading cause of fetal death, infant mortality and morbidity in childhood. According to the EUROCAT estimates, of the 5.1 million births in the European Union (EU) each year approximately 127,000 (2.5%) have a congenital anomaly. EUROCAT is a European network of population-based registries whose objectives are to provide essential epidemiologic information on congenital anomalies in Europe, to facilitate the early warning of new teratogenic exposures and to evaluate the effectiveness of primary prevention. Each year, EUROCAT performs statistical monitoring for both trends and clusters in time on 84 anomaly subgroups. The results of the statistical monitoring are the basis for instigating possible further investigations at the local registry level. The present report shows the results of the monitoring performed on data for the birth years 2008-2017 by the JRC-EUROCAT Central Registry. Cases of congenital anomaly among livebirths, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly following prenatal diagnosis at any gestational age were included. We report both the statistical results and, where available, the outcome of the preliminary investigations conducted by registries.JRC.F.1-Health in Societ

Physicochemical characterisation of gold, silica and silver nanoparticles in water and in serum-containing cell culture media

This report presents the results from a study organised under the coordination of JRC as part of a project aiming at the adaptation of the in vitro micronucleus test (Test Guideline 487) for the assessment of manufactured NMs. The aim of the first step of the project was to evaluate the physicochemical characterisation of selected representative nanomaterials (5 nm gold, 30 nm gold, 22 nm silica, 30 nm citrate and 30 nm PVP stabilised silver nanoparticles) in pure water and in different complete culture media. The results of the study show that using a combination of different characterisation techniques is important to providing reliable information about the agglomeration behaviour of the tested nanoparticles in complete cell culture media (CCM). Most of the materials exhibited mild agglomeration in serum containing CCM. Only the PVP functionalised silver nanoparticles showed a size distribution change in all of the culture media that is so small that it could be attributed to solely protein adsorption without notable agglomeration. Silica nanoparticles were found to be the most sensitive to interaction with serum containing CCM, showing massive concentration and time dependent agglomeration strongly affected by the CCM composition. Extensive agglomeration might lead also to the accelerated sedimentation of the particles changing drastically the true, effective dose that the cells will receive under in vitro conditions1, 2. Thus, it has to be investigated in more detail and taken in account when designing in vitro experiments in the next phase of the project.JRC.F.2-Consumer Products Safet

Dispersion Behaviour of Silica Nanoparticles in Biological Media and Its Influence on Cellular Uptake

Given the increasing variety of manufactured nanomaterials, suitable, robust, standardized in vitro screening methods are needed to study the mechanisms by which they can interact with biological systems. The in vitro evaluation of interactions of nanoparticles (NPs) with living cells is challenging due to the complex behaviour of NPs, which may involve dissolution, aggregation, sedimentation and formation of a protein corona. These variable parameters have an influence on the surface properties and the stability of NPs in the biological environment and therefore also on the interaction of NPs with cells. We present here a study using 30 nm and 80 nm fluorescently-labelled silicon dioxide NPs (Rubipy-SiO2 NPs) to evaluate the NPs dispersion behaviour up to 48 hours in two different cellular media either supplemented with 10% of serum or in serum-free conditions. Size-dependent differences in dispersion behaviour were observed and the influence of the living cells on NPs stability and deposition was determined. Using flow cytometry and fluorescence microscopy techniques we studied the kinetics of the cellular uptake of Rubipy-SiO2 NPs by A549 and CaCo-2 cells and we found a correlation between the NPs characteristics in cell media and the amount of cellular uptake. Our results emphasize how relevant and important it is to evaluate and to monitor the size and agglomeration state of nanoparticles in the biological medium, in order to interpret correctly the results of the in vitro toxicological assays.JRC.I.4-Nanobioscience

Modulation of surface bio-functionality by using gold nanostructures on protein repellent surfaces

The integration of gold nanoparticles (Au NPs) or nanostructures with special optical properties on solid surfaces has become a major research topic in the field of nanobiotechnology in particular for the development of new generation of multifunctional bioanalytical platforms. This has led to considerable research efforts for developing quick and direct nanofabrication methods capable of producing well-ordered 2D nanostructured arrays with tunable morphological, chemical and optical properties. In this paper, we propose a simple and fast nanofabrication method enabling the creation of Au NPs patterns on a non-adhesive and cell repellent plasma-deposited poly(ethyleneoxide) (PEO-like) coating. The immobilization of Au NPs on PEO-like coatings does not require any prior chemical modifications and is achieved by a straightforward and stable self-assembly technique. By varying the size and the concentration of the Au NPs it is possible to control the Au NPs density and spatial distribution on the PEO-like coated surface with direct effects on the bio-functionality of the surface. These nanostructured surfaces have been tested for protein bio-recognition analysis and as a cell culture platform. The developed nanostructured platform has many potential applications in the field of protein-nanoparticle and cell-nanoparticle interaction studies, nanotoxicology and bioengineering.JRC.I.4-Nanobioscience

ECVAM Technical Report on the Status of Alternative Methods for Cosmetics Testing (2008-2009)

The ECVAM technical report presents the progress made in the development and validation of alternative methods for the human health effects relevant to the Cosmetics Directive. It provides an update on the activities described by ECVAM in 2005 , 2006 and 2007 . The report intends to present the latest scientific and technical developments in the field during 2008-2009. As required by Directive 2003/15/EC, the seventh amendment to Directive 76/768/EEC, developments in refinement and reduction methods are also described (EU, 2003). Most successes in the development of alternative methods are in acute local toxicity and short-term testing, such as e.g. skin and eye irritation/corrosion, phototoxicity and skin penetration The test methods consuming a high number of animals, however, are in long-term testing and systemic toxicity, such as e.g. reproductive toxicity and repeated dose toxicity. In these complex fields, several research initiatives are ongoing. However full replacement approaches are still lacking.JRC.DG.I.3-In-vitro method

The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD(50)>2000mg/kg b.w.).Peer Reviewe