Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

Peer reviewe

The Risk Thermometer - A tool for risk comparison

<p>In this project, the first version of the Risk Thermometer for comparison of chemical risks associated with chronic exposure via food (i.e., not acute effects) has been developed. This tool can for example be used to assess and compare exposures to environmental contaminants, pesticides, food additives, chemicals used in food contact materials, as well as minerals/nutrients. A public consultation on the draft report on the Risk Thermometer was held between 2014-12-17 and 2015-02- 28. The public consultation helped to improve the final product.</p> <p>The Risk Thermometer consists of four parts: 1) a severity-adjusted margin of exposure (SAMOE) approach, which is an extension of the present approach for chemical risk characterization, 2) a model that describes the uncertainty in the SAMOE, 3) a risk classification approach that categorizes the SAMOE value in terms of health concern levels, and 4) a graphical illustration of the results. The present report focuses on the underlying parts (1, 2, and 3) of the Risk Thermometer, and while examples of illustrations are included the graphical front end of the tool (part 4) will be further developed.</p> <p>By choice the Risk Thermometer is based on both scientific considerations (risk assessment) and value-based considerations (risk management). The tool is regarded to bridge the three elements of risk analysis (risk assessment, risk management, and risk communication. It is, however, in line with the important principle of an operational separation between the three sectors. The Risk Thermometer provides the Swedish National Food Agency (NFA) with a new approach for priority-setting, and contributes for example to the further development of a risk-based food control. Importantly, results from the Risk Thermometer represent one basis for risk management. For example, they apply to the target population under investigation. Thus, aspects of total public health burden, taking population size into consideration is not explicitly included. Such factors need to be accounted for separately as part of further risk management. The Risk Thermometer also aims to communicate levels of risks to consumers, the media, and other stakeholders, and it is anticipated that it will clarify the results of quantitative risk assessments performed by the NFA. As noted above, the graphical illustration of the results (part 4 of the tool) that relates to risk communication will be further developed. In general, updates of the Risk Thermometer will be considered as experience of using this approach in the process of risk analysis increases.</p> <p>To satisfy the objectives of the Risk Thermometer a framework for comparative risk characterization has been developed that efficiently can be integrated in today’s risk assessment, risk management, and risk communication workflow at the NFA. Such a practical framework needs to be based on current risk assessment methodology, including data requirements as well the use of default values (e.g., adjustment factors, AFs), to a high extent. These considerations have been important for the selection and design of the SAMOE approach.</p> <p>The minimum data requirement for the SAMOE approach is 1) an estimate of the exposure to a chemical in the target population, and 2) a reference point (RP) like the benchmark dose (BMD). These are the main inputs currently used for quantitative risk characterization of chemicals where an RP, or similar, is compared to the exposure using the margin of exposure (MOE), or MOE related concept. Thus, for chemicals the risk is generally described by a MOE. The MOE indirectly relates to the probability of occurrence (or change in the response) of a health effect.However, the severity of the health effect is also an important element of the risk concept which is generally not accounted for by the MOE. This consideration is of particular relevance herein since the objective of the Risk Thermometer involves comparative risk characterization across chemicals and health effects in contrast to applications of the traditional MOE approach. The SAMOE approach addresses this issue by penalizing the traditional MOE value depending on the severity of the critical health effect used as basis for risk assessment. This is achieved by the systematic use of a severity factor (SF). The SF is determined from a developed health effect classification scheme. This scheme is a key element of the SAMOE approach, and differentiates the SAMOE approach from the traditional MOE, or MOE related concepts.</p> <p>A semi-quantitative model for describing the uncertainty in the SAMOE estimate has also been developed. This method involves determining the level and direction of uncertainties associated with each of the parameters of the SAMOE. Whenever possible data driven input are used in this model, and if data is not available semi-quantitative standards are used instead. The overall uncertainty in the SAMOE is in addition to the point estimate accounted for in the risk classification approach discussed below. Using a risk classification approach the SAMOE estimate is categorized in terms of health concern levels. The approach for risk classification currently consists of five Risk Classes. The main purpose of the risk classification, and the underlying SAMOE metric, is to describe chemical risks on a comparative scale. The NFA may further develop the risk classification approach regarding statements about the level of health concern that is associated with each Risk Class.</p> <p>In the interim, the Risk Thermometer is considered not to be fundamentally more protective/conservative than the traditional risk assessment approach. It is regarded that exposures (at population level) that are in the range of a traditional healthbased guidance value, or similar, would most likely classify in Risk Class 3 (lowto- moderate concern), which represents the midpoint of the risk classification scale. Exposures in Risk Class 3 may depending on the particular situation require application of risk management measures, including dietary advice or regulatory initiatives, and collection of more information to fill data gaps. From a risk perspective, the application of such measures is more likely to be relevant in the case of exposures categorizing in Risk Class 4 and 5, while it seems not likely to be needed in the case of exposures categorizing in Risk Class 1 and 2.</p> <p>There are challenges associated with the present as well as future approaches for comparing food related risks. However, the use of such methodology is regarded as an improvement. For example, it increases the transparency by which the severity of effect influences statements regarding health concerns associated with chemical exposures. In general, the area of chemical risk assessment is regarded to benefit from the introduction of approaches that forces the interpretation of exposures or risks in a greater context. Public interests concerning potential health risks associated with food consumption may benefit from such developments, as well as the health agencies that need to prioritize the use of their resources with respect to risk related questions.</p