Subchronic Inhalation Toxicity Study with a Vapor-Grown Carbon Nanofiber in Male and Female Rats (OECD 413): Does Nanofiber Exposure Have Adverse Impacts on the Cardiovascular System?

Abstract

The objective of this 90-day inhalation toxicity study in male/female rats exposed to vapor-grown carbon nanofibers (CNF) was to assess both the lung toxicity and systemic (cardiovascular) effects following exposures to 0, 0.54, 2.5, or 25 mg/m³. From a respiratory tract standpoint, there was some minor histopathological, cell proliferative, and inflammatory effects at the highest concentration—25 mg/m³. In addition, there was some evidence that aerosol exposures at the highest concentration (25 mg/m³) resulted in a minimal translocation of the inhaled nanofibers from the respiratory tract to systemic extrapulmonary sites in the body. This finding led to the hypothesis that the movement of inhaled fibers into the systemic bloodstream could facilitate a cross-talk relationship between the respiratory tract and cardiovascular effects, thus impacting blood coagulation effects. Accordingly, common cardiovascular/coagulation indices were measured—including cardiomyocyte proliferation parameters; systemic inflammation indices—such as C-reactive protein and four different coagulation parameters: (1) fibrinogen levels; (2) platelet counts; (3) PT; and (4) aPTT bleeding times. The results demonstrated no significant differences were measured between air and high dose, CNF-exposed rats. It was concluded that no apparent cross-talk was demonstrated between local respiratory and systemic/cardiovascular endpoints. Based upon the data generated in this 90-day, subchronic inhalation study, it seems likely that the pulmonary toxicity endpoints of this study would be useful in accurately predicting lung inflammatory outcomes in a shorter-term inhalation study. However, the pulmonary histopathology and cardiovascular endpoints described in this study likely require the subchronic inhalation testing exposure protocol.