Table 9.

CARBON-study; design, dosage, administration

In order to measure the single effect of the carbon nanoparticles, we selected neutral, apolar, round, onion-like, and pure carbon nanoparticles which resemble the carbon particles in air pollution concerning particle characteristics. We aimed the dosage of the final-product to be in line with normal, daily life exposure concentrations. Dosages were calculated according to the European Medicines Agency (EMA) First-In-Man (FIM) guidelines based on the No Observed Adverse Effect Level (NOAEL) in non-clinical safety studies adjusted with allometric factors. These dosages are comparable with the mean exposure concentration of PM 2.5 (particles smaller than 2.5 μm) during public fireworks at New Year’s Day at the first hour of the year, as measured by the Dutch National Air Quality Monitoring Network and previous research in the Netherlands by Strak et al. [17]

We used the well-described and safe method of bronchial segmental challenge [18, 19] to deliver the nanoparticles to the lungs. An important advantage of this model, as compared to inhalation of diesel exhaust in an inhalation chamber, is that the exposure is limited to only one component (carbon nano particles) in only one subsegment of the lung, thereby reducing the risk of generalized bronchoconstriction. In the past we safely performed bronchial segmental challenges with house dust mite allergen and lipopolysaccharide in healthy subjects as well as patients with mild asthma [18, 19]. Based upon the thorough analysis of the final product to be used and the careful considerations regarding the dosage and method of administration, the institutional ethics committee approved the study.