Nanotoxicology: Concepts and Research Needs.

Reports about the potential of ENMs to cause adverse health effects has raised serious concerns, leading to the widespread belief that engineered NPs are ‘toxic’ in general and represent a significant risk for human and environmental health.  However, a perceived risk needs to be clearly separated from scientific facts, because such perception is most often based on unrealistic toxicity tests that were performed with extraordinary high doses; a hazard established this way needs to be clearly separated from a risk, and a perceived risk from scientific facts.  Knowledge about potential human and environmental exposure combined with dose-response toxicity information will be necessary to determine real or perceived risks of nanomaterials following inhalation, oral or dermal routes of exposure.  The respiratory tract is the major portal of entry for airborne nanoparticles ; using this exposure route as an example, some key concepts of nanotoxicology will be discussed, including the significance of dose, dose rate, dosemetric, and biokinetics.  The importance of characterizing critical physico-chemical properties of nanoparticles is emphasized, specifically surface properties that influence their biological/toxicological properties, cell-interactions and biokinetics.  Thus, for example, the appropriateness of altering nanoparticle surface characteristics via use of dispersants or by harsh sonication procedures in preparation for toxicity testing needs to be critically evaluated.   Misconceptions need to be corrected, such as the propensity of nanoparticles to translocate with high efficiency across barriers, or that the identification of a hazard based on unrealistic and unjustifiable high dose studies represents a useful basis for risk assessment.  On the other hand, study results based on improbable high doses, in vitro as well as in vivo, may be viewed as proof-of-principle studies to be validated by appropriately designed follow-up studies using justifiable exposures.  Under such realistic conditions, many engineered nanoparticles may be unlikely to induce adverse effects, although still largely unknown are effects of chronic, low level exposures.  Validation of in vitro results by in vivo studies is essential and should be based on dosimetric and biokinetic information; extrapolation from animal studies to humans requires careful analysis and interpretation of dose-response data.  Without being able to perform an appropriate risk assessment for a specific nanomaterial, it is prudent to prevent exposures by precautionary measures/regulations.