Hazard and Risk Characterization of Inhaled Carbon Nanomaterials

The rapid introduction of nanotechnology in manufactured goods for diverse industrial applications and consumer uses promises great benefits, which – however – may be significantly offset because of toxicity implications. Indeed, serious concerns have been expressed about risks posed by exposure to engineered nanomaterials (ENMs), their potential to cause undesirable health effects, contaminate the environment and thereby adversely affect living systems. For example, carbon and TiO₂ nanoparticles inhaled by rats at extraordinarily high concentrations in chronic studies induced lung tumors due to lung overloading, although these are generally considered to be rather benign materials. As anther example, carbon nanotubes administered acutely to rats and mice as bolus or by inhalation of high concentrations induced significant pulmonary inflammation, and intraperitoneal and intrapleural injections of multi-walled carbon nanotubes (MWCNT) caused pleural granulomatous and mesothelioma responses. In contrast to carbon black nanoparticles, these findings caused great concern about asbestos-like long-term toxicity and carcinogenicity of fiber-shaped nanomaterials which seriously questions as to whether simply particle overload could explain these findings. Although subsequent three-month subchronic rat inhalation studies with MWCNT did not result in carcinogenicity and a No Observed Adverse Effect Level and Low Observed Adverse Effect Level were identified, the short exposure duration of these studies is insufficient for identifying a carcinogenic risk. New data on translocation and clearance mechanisms of inhaled MWCNT to pleural tissue and other target sites have to be considered. A concept of assessing nanomaterial safety based on subchronic inhalation studies with multi-walled carbon nanotubes and based on a comparison to positive and negative benchmark materials will be discussed, emphasizing the importance of using full exposure-dose-response relationships and using different dosemetrics for identifying and ranking a hazard and characterizing risks for deriving occupational exposure levels.