The impact of nanomaterial characteristics on inhalation toxicity.

During the last few decades, nanotechnology has evolved into a success story, apparent from a steadily increasing number of scientific publications as well as a large number of applications based on engineered nanomaterials (ENMs). Its widespread uses suggest a high relevance for consumers, workers and the environment, hence justifying intensive investigations into ENM-related adverse effects as a prerequisite for nano-specific regulations. In particular, the inhalation of airborne ENMs, being assumed to represent the most hazardous type of human exposure to these kinds of particles, needs to be scrutinized. Due to an increased awareness of possible health effects, which have already been seen in the case of ultrafine particles (UFPs), research and regulatory measures have set in to identify and address toxic implications following their almost ubiquitous occurrence. Although ENM properties differ from those of the respective bulk materials, the available assessment protocols are often designed for the latter. Despite the large benefit ensuing from the application of nanotechnology, many issues related to ENM behavior and adverse effects are not fully understood or should be examined anew. The traditional hypothesis that ENMs exhibit different or additional hazards due to their "nano" size has been challenged in recent years and ENM categorization according to their properties and toxicity mechanisms has been proposed instead. This review summarizes the toxicological effects of inhaled ENMs identified to date, elucidating the modes of action which provoke different mechanisms in the respiratory tract and their resulting effects. By linking particular mechanisms and adverse effects to ENM properties, grouping of ENMs based on toxicity-related properties is supposed to facilitate toxicological risk assessment. As intensive studies are still required to identify these "ENM classes", the need for alternatives to animal studies is evident and advances in cell-based test systems for pulmonary research are presented here. We hope to encourage the ongoing discussion about ENM risks and to advocate the further development and practice of suitable testing and grouping methods.