Nanomaterial-Induced Extra-Pulmonary Health Effects - the Importance of Next Generation Physiologically Relevant In Vitro Test Systems for the Future of Nanotoxicology.

Manufactured nanomaterials (NMs) offer incredible scientific and societal benefits but their potential hazard to human health is not yet fully comprehended. In the last decade, a significant body of evidence indicates that certain NMs are capable of translocating from the primary exposure site (skin, lungs and gastrointestinal tract) to a number of secondary organs which includes the liver. Moreover, recent advances in the field of nanomedicine has resulted in increasing direct intravenous injection of NMs with the liver being a particularly important organ with regards to potential toxic effects and accumulation of said materials. It is generally acknowledged that it is not always possible to make direct or meaningful comparisons between in vitro and in vivo xenobiotic-induced toxicological responses. One of the main reasons for the lack of comparability between the testing strategies is that biological responses are not often alike which can in part be attributed to the numerous limitations of traditional mono-cellular in vitro test systems which are acting as a surrogate for a whole organ. In an attempt to address and highlight this important issue, this chapter will discuss the progress made in the production and validation oof next generation more physiologically relevant multi-cellular in vitro models of skin, GIT and the liver utilised for the assessment of the NM-induced toxicological effects.