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Around 25% of the children in developed countries are affected with immune-based diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune diseases have shown increasing prevalences in the last decades. The role of chemical exposures in these phenomena is unclear. It is thought that the developmental immune system is more susceptible to toxicants than the mature situation. Developmental immunotoxicity (DIT) testing is nowadays not or minimally included in regulatory toxicology requirements. We reviewed whether developmental immune parameters in rodents would provide relatively sensitive endpoints of toxicity, whose inclusion in regulatory toxicity testing might improve hazard identification and risk assessment of chemicals. For each of the nine reviewed toxicants, the developing immune system was found to be at least as sensitive or more sensitive than the general (developmental) toxicity parameters. Functional immune (antigen-challenged) parameters appear more affected than structural (non-challenged) immune parameters. Especially, antibody responses to immune challenges with keyhole limpet hemocyanine or sheep red blood cells and delayed-type hypersensitivity responses appear to provide sensitive parameters of developmental immune toxicity. Comparison with current tolerable daily intakes (TDI) and their underlying overall no observed adverse effect levels showed that for some of the compounds reviewed, the TDI may need reconsideration based on developmental immune parameters. From these data, it can be concluded that the developing immune system is very sensitive to the disruption of toxicants independent of study design. Consideration of including functional DIT parameters in current hazard identification guidelines and wider application of relevant study protocols is warranted. [ABSTRACT FROM AUTHOR]

This manuscript describes the follow-up study of our previous publication on the presence and risks of nanosilica in food. New information on the presence of nanosilica in the gastrointestinal tract is evaluated and information on nanosilica and synthetic amorphous silica (SAS) is compared to assess its relevance for risk assessment of nanosilica in food. Irrespective of whether SAS should be regarded as a nanomaterial or a non-nanoform of silica, a comparison to nanosilica is relevant to determine whether there are differences in physicochemical properties, which may lead to differences in toxicity. Based on this comparison, knowledge gaps are identified and recommendations for a targeted approach to facilitate risk assessment of nanosilica in food are given. Considering the discussion to which extent nanomaterials with (slightly) different physicochemical characteristics can be grouped for risk assessment - the sameness issue - actual exercises as presented in this manuscript are highly relevant for bringing this discussion forward. [ABSTRACT FROM AUTHOR]

Abstract: Risk managers need detailed information on (1) the type of effect, (2) the size (severity) of the expected effect(s) and (3) the fraction of the population at risk to decide on well-balanced risk reduction measures. A previously developed integrated probabilistic risk assessment (IPRA) model provides quantitative information on these three parameters. A semi-quantitative tool is presented that combines information on these parameters into easy-readable charts that will facilitate risk evaluations of exposure situations and decisions on risk reduction measures. This tool is based on a concept of health impact categorization that has been successfully in force for several years within several emergency planning programs. Four health impact categories are distinguished: No-Health Impact, Low-Health Impact, Moderate-Health Impact and Severe-Health Impact. Two different charts are presented to graphically present the information on the three parameters of interest. A bar plot provides an overview of all health effects involved, including information on the fraction of the exposed population in each of the four health impact categories. Secondly, a Health Impact Chart is presented to provide more detailed information on the estimated health impact in a given exposure situation. These graphs will facilitate the discussions on appropriate risk reduction measures to be taken. [Copyright &y& Elsevier]

Biological monitoring is a useful tool to assess occupational and environmental exposure following a wide range of chemical incidents. Guidance values are available from international organisations to help interpret the result of biological monitoring. In addition, guidance values based on the 90th percentile of biological monitoring data obtained under conditions of good exposure control may help identify lapses in control and the need for remedial action to improve controls and reduce risk. In all cases interpretation of biomonitoring results following incidents needs care and in particular reference to the time of sample collection and basis of the guidance values. Biomonitoring guidance values specifically derived for chemical incident scenarios are not available but would be of great help to interpret biological monitoring results. [ABSTRACT FROM AUTHOR]

Biological monitoring in humans (HBM) is widely used in the field of occupational and environmental health. In the situation of an unexpected release of hazardous materials HBM may contribute to the medical support and treatment of exposed individuals from the general population or of emergency responders. Such exposure information may also be used to respond to individual concerns such as questions about a possible relationship between the chemicals released during the incident and health effects. In The Netherlands a guideline was prepared to support early decision-making about the possible use of HBM for exposure assessment during or as soon as possible following a chemical incident. The application of HBM in such an emergency setting is not much different from situations where HBM is normally used but there are some issues that need extra attention such as the choice of the biomarker, the biological media to be sampled, the time point at which biological samples should be collected, the ethics approval and technical implementation of the study protocol and the interpretation and communication of the study results. These issues addressed in the new guideline will support the use of HBM in the management of chemical disasters. [ABSTRACT FROM AUTHOR]

Abstract: A statistical model is presented extending the integrated probabilistic risk assessment (IPRA) model of van der Voet and Slob [van der Voet, H., Slob, W., 2007. Integration of probabilistic exposure assessment and probabilistic hazard characterisation. Risk Analysis, 27, 351–371]. The aim is to characterise the health impact due to one or more chemicals present in food causing one or more health effects. For chemicals with hardly any measurable safety problems we propose health impact characterisation by margins of exposure. In this probabilistic model not one margin of exposure is calculated, but rather a distribution of individual margins of exposure (IMoE) which allows quantifying the health impact for small parts of the population. A simple bar chart is proposed to represent the IMoE distribution and a lower bound (IMoEL) quantifies uncertainties in this distribution. It is described how IMoE distributions can be combined for dose-additive compounds and for different health effects. Health impact assessment critically depends on a subjective valuation of the health impact of a given health effect, and possibilities to implement this health impact valuation step are discussed. Examples show the possibilities of health impact characterisation and of integrating IMoE distributions. The paper also includes new proposals for modelling variable and uncertain factors describing food processing effects and intraspecies variation in sensitivity. [Copyright &y& Elsevier]