Determination of the delivered dose of nanoparticles in the trachea-bronchial and alveolar regions of the lung

Abstract

Particle dosimetry is a necessary step for the risk assessment especially with regard to toxicological effects of nanoparticles. In many cases, dosimetry is linked to exposure via the surface area of the nanoparticles. Due to interface dependent reactions of particles and the lung tissue poorly soluble particles (PSP) are particularly in the focus of interest. In recent years the measurement the geometric particle surface area concentration, GSA, in the air and determination of the lung deposited surface area (LDSA) based on lung deposition models gained interest. The effective particle concentration in the Lung (LDSA) cannot be measured directly. The maxima of many common airborne particle surface area distributions occur in the particle size range below 400 nm. High alveolar and trachea-bronchial deposition can be encountered in this size range.In general, it is very difficult to measure the particle surface area directly. To measure particle surface area concentration in aerosols, online instruments were developed (e.g. nanoparticle surface area monitor - NSAM). These instruments are based on unipolar particle charging. To determine the charge level of single particles as a function of the particle size, the current of monodisperse particles is divided by the aerosol number concentration. In order to relate the total measured current of the entire size-distributions, the instrument response function has to have the same slope as the size-dependent particle surface area. Calibration allows putting these curves on top of each other at one specific particle size (no error). Any deviations of the two curves at other sizes cause errors.The first instrument based on this principle was NSAM. Its response function for the measurement of spherical particles shows a diameter dependency of d1.16. It was found that if the geometric surface area (GSA) of a particle is multiplied with the alveolar deposited fraction (alveolar deposition curve of the ICRP-model) the resulting curve has almost the same slope as the NSAM response function. In principle, this concept also works for the comparison with the deposition in the trachea-bronchial region. To date, only the LDSA (alveolar or trachea-bronchial) of spherical particles in human lungs based on the ICRP-model can be determined by the available instruments.To extend the application range of NSAM to other lung deposition models, e.g. the Multiple-Path Particle Dosimetry model (MPPD) which also provides the possibility to investigate particle deposition in animal lungs, we defined model-specific calibration factors. This allowed the correct determination of the surface area concentration at the calibration point (100 nm) and also facilitated the measurement at other particle diameters.We assessed whether the slope differences between the modified instrument responses and the calculated LDSA in the MPPD deposition models led to tolerable errors. First, we described the calculation of these errors as a function of the particle size. Using these size-dependent error functions the total error (for the measurement of an entire particle size distribution) can be determined if e.g. a known particle number size distribution is transferred into a surface area distribution. To present a possibility to estimate the errors without performing the described error calculations, we performed a systematic study. We determined the total error concerning the measurement of LDSA for two ambient real aerosols (combustion of diesel and firewood). For these very different particle size distributions and models for different animals, the errors were below 20%, which seemed tolerable. Therefore NSAM and other instruments with a similar working principle can be used to determine the LDSA with regard to particle deposition in human and animal lungs.