Usefulness of currently available in vitro methods for toxicity assessment of nanoparticles and nanomaterials

Introduction
It is becoming increasingly widely recognized that substances in nano form can exert different biological effects in comparison to bulk form (e.g. induction of cytotoxicity, inflammation, genotoxicity, or oxidative stress). As nanoparticles and nanomaterials are used in increasing number of workplaces, the need for testing their potential toxic properties in pristine form as well as in end-products is obvious.

Methods
There are validated methods for toxicity assessment of chemicals in standard from or medical devices under OECD, EU or ISO, however their usefulness in testing substances in nano form is still under debate. According to currently available toxicity testing strategies, in vitro methods always precede in vivo testing.

Results
Although in vitro methods offer great advantages (e.g. speed, high-throughput potential, relatively low costs) growing number of reports indicate potential problems and pitfalls in using such methods for assessment of nano forms. Problems such as, inappropriate dispersion, non-specific interference with read-out systems, protein binding, secondary genotoxicity, etc. are among the most frequently reported. Considering the problems it is of the utmost importance first to understand complex nanoparticle-cell interactions, and then building upon the knowledge gained, to develop new or accordingly modify existing testing methods for nano forms.

Discussion
Problems will be described based on the literature and own experience and recommendations given.