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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]