Ingredients for a Dutch radon action plan, based on a national survey in more than 2500 dwellings.

A new Euratom directive demands that Member States establish a national action plan for indoor radon. Important requirements are a national reference level for the radon concentration in dwellings, actions to identify dwellings with radon concentrations that might exceed this reference level and the encouragement of appropriate measures to reduce the radon concentrations in dwellings where these are high. This paper provides ingredients and recommendations for a national action plan for radon in dwellings, applicable to the Netherlands. The approach presented here, which may serve as a model for other countries or regions with a comparatively favourable indoor radon situation, is based on the analysis of radon data from a national survey in more than 2500 Dutch dwellings, built since 1930. The annual average activity concentration of radon in dwellings in the Netherlands equals 15.6 ± 0.3 Bq m-3. The 50th and 95th percentiles were found to be 12.2 and 38.0 Bq m-3, respectively. In 0.4 per cent of the dwellings we found values above 100 Bq m-3. Radon concentrations showed correlations with type of dwelling, year of construction, ventilation system, soil type and smoking behaviour of inhabitants. The survey data suggest that it is feasible for the Netherlands to adopt a national reference level for radon in dwellings of 100 Bq m-3, in line with recommendations by WHO and ICRP. We were able to predict dwellings with a moderate probability for radon concentrations above 100 Bq m-3 by applying a combination of three selection criteria: location, type of dwelling and manner of ventilation. Of the existing 6.2 million dwellings in the Netherlands (built since 1930), approximately 23-24 thousand are suspected to exceed this level. Some 80% of these are found in the group of naturally ventilated single-family dwellings in either the southern part of Limburg (approx. 13 thousand) or the Meuse-Rhine-Waal river delta (approx. six thousand). This selected group of dwellings represents 7% of the housing stock. In contrast to many other countries in Europe and elsewhere, radon concentrations in dwellings above 200 Bq m-3 are very rare in the Netherlands. As a result, relatively simple and inexpensive measures in existing Dutch single-family dwellings will be sufficient to reduce indoor radon concentrations above the proposed national reference level of 100 Bq m-3 to values well below.

Design and synthesis of novel small molecule CCR2 antagonists: evaluation of 4-aminopiperidine derivatives.

A novel N-(2-oxo-2-(piperidin-4-ylamino)ethyl)-3-(trifluoromethyl)benzamide series of human CCR2 chemokine receptor antagonists was identified. With a pharmacophore model based on known CCR2 antagonists a new core scaffold was designed, analogues of it synthesized and structure­affinity relationship studies derived yielding a new high affinity CCR2 antagonist N-(2-((1-(4-(3-methoxyphenyl)cyclohexyl)piperidin-4-yl)amino)-2-oxoethyl)-3-(trifluoromethyl)benzamide.

Climate change and food safety: an emerging issue with special focus on Europe.

According to general consensus, the global climate is changing, which may also affect agricultural and livestock production. The potential impact of climate change on food security is a widely debated and investigated issue. Nonetheless, the specific impact on safety of food and feed for consumers has remained a less studied topic. This review therefore identifies the various food safety issues that are likely to be affected by changes in climate, particularly in Europe. Amongst the issues identified are mycotoxins formed on plant products in the field or during storage; residues of pesticides in plant products affected by changes in pest pressure; trace elements and/or heavy metals in plant products depending on changes in their abundance and availability in soils; polycyclic aromatic hydrocarbons in foods following changes in long-range atmospheric transport and deposition into the environment; marine biotoxins in seafood following production of phycotoxins by harmful algal blooms; and the presence of pathogenic bacteria in foods following more frequent extreme weather conditions, such as flooding and heat waves. Research topics that are amenable to further research are highlighted.

Early identification systems for emerging foodborne hazards.

This paper provides a non-exhausting overview of early warning systems for emerging foodborne hazards that are operating in the various places in the world. Special attention is given to endpoint-focussed early warning systems (i.e. ECDC, ISIS and GPHIN) and hazard-focussed early warning systems (i.e. FVO, RASFF and OIE) and their merit to successfully identify a food safety problem in an early stage is discussed. Besides these early warning systems which are based on monitoring of either disease symptoms or hazards, also early warning systems and/or activities that intend to predict the occurrence of a food safety hazard in its very beginning of development or before that are described. Examples are trend analysis, horizon scanning, early warning systems for mycotoxins in maize and/or wheat and information exchange networks (e.g. OIE and GIEWS). Furthermore, recent initiatives that aim to develop predictive early warning systems based on the holistic principle are discussed. The assumption of the researchers applying this principle is that developments outside the food production chain that are either directly or indirectly related to the development of a particular food safety hazard may also provide valuable information to predict the development of this hazard.

Development of a QSAR for worst case estimates of acute toxicity of chemically reactive compounds.

Future EU legislations enforce a fast hazard and risk assessment of thousands of existing chemicals. If conducted by means of present data requirements, this assessment will use a huge number of test animals and will be neither cost nor time effective. The purpose of the current research was to develop methods to increase the acceptability of in vitro data for classification and labelling regarding acute toxicity. For this purpose, a large existing database containing in vitro and in vivo data was analysed. For more than 300 compounds in the database, relations between in vitro cytotoxicity and rat or mouse intravenous and oral in vivo LD50 values were re-evaluated and the possibilities for definition of mechanism based chemical subclasses were investigated. A high in vitro-in vivo correlation was found for chemicals classified as irritants. This can be explained by a shared unspecific cytotoxicity of these compounds which will act as the predominant mode of action for both endpoints, irritation and acute toxicity. For this subclass, which covered almost 40% of all compounds in the database, the LD50 values after intravenous dosing could be predicted with high accuracy. A somewhat lower accuracy was found for the prediction of oral LD50 values based on in vitro cytotoxicity data. Based on this successful correlation, a classification and labelling scheme was developed, that includes a hazard based definition of the applicability domain (irritants) and a prediction of the labelling of compounds for their acute iv and oral toxicity. The scheme was tested by an external validation.

Critical effect sizes in toxicological risk assessment: a comprehensive and critical evaluation.

A key issue in toxicological risk assessment is determining the effect level below which there is no reason for concern. In the Benchmark approach, this breaking point between adverse and non-adverse is called the critical effect size (CES). This study aimed to investigate the possibilities to determine CESs for toxicological effect parameters commonly used in human risk assessment and includes a literature review and an opinion analysis among European toxicologists. The results indicate that the current knowledge is insufficient to define CESs for all individual parameters. Furthermore, the use of a single universal CES seems no option. It is concluded that it is not yet possible to reach international consensus on CESs for most toxicological parameters. However, every parameter for which consensus on the CES is reached is a step forward, because this can facilitate discussions on the adversity and relevance of certain changes in that parameter, irrespective of the method applied in risk assessment.