There are certain concerns regarding the safety for the environment and human health from the use of engineered nanoparticles (ENPs), which leads to unintended exposures, in contrast to the use of ENPs for medical purposes. Animal experiments have shown that investigated ENPs (metallic nanoparticles, quantum dots, carbon nanotubes) can translocate to the brain from different entry points (skin, blood, respiratory pathways). After inhalation or instillation into parts of the respiratory tract a very small fraction of the inhaled or instilled ENPs reaches the blood and subsequently secondary organs, including the central nerve system, at a low translocation rate. Experimental in vivo and in vitro studies have shown that several types of ENPs can have various biological effects in the nervous system. However, the relevance of these data for risk assessment is far from clear. It is, however, unlikely that acute high dose exposures would occur. The risk from such exposures to damage the central nerve system is thus probably even lower. This dossier focuses on the unintended human exposure of ENPs. In particular, possible effects on the functions or processes in the brain are discussed and an attempt to assess the risks is performed. However, the present state of knowledge is unsatisfactory for a proper risk assessment in this area.