Respiratory system deposition

Pharmaceutical powder aerosols have more stringent requirements placed upon the formulation regarding moisture, particle size, and the valve. For metered-dose inhalers, the dispensed product must be deflvered as a spray having a relatively small (3—6 -lm) particle size so that the particles can be deposited at the proper site in the respiratory system. On the other hand, topical powders must be formulated to minimize the number of particles in the 3—6-p.m range because of the adverse effects on the body if these materials are accidently inhaled. 

B. Removal of Deposited Particles from the Respiratory System... 

The respiratory system has several mechanisms for removing deposited particles (8). The walls of the nasal and tracheobronchial regions are coated with a mucous fluid. Nose blowing, sneezing, coughing, and swallowing... 

Health effects attributed to sulfur oxides are likely due to exposure to sulfur dioxide, sulfate aerosols, and sulfur dioxide adsorbed onto particulate matter. Alone, sulfur dioxide will dissolve in the watery fluids of the upper respiratory system and be absorbed into the bloodstream. Sulfur dioxide reacts with other substances in the atmosphere to form sulfate aerosols. Since most sulfate aerosols are part of PMj 5, they may have an important role in the health impacts associated with fine particulates. However, sulfate aerosols can be transported long distances through the atmosphere before deposition actually occurs. Average sulfate aerosol concentrations are about 40% of average fine particulate levels in regions where fuels with high sulfur content are commonly used. Sulfur dioxide adsorbed on particles can be carried deep into the pulmonary system. Therefore, reducing concentrations of particulate matter may also reduce the health impacts of sulfur dioxide. Acid aerosols affect respiratory and sensory functions. 

The aerodynamic particle diameter determines the fate of particles in the respiratory system. Coarse particles are deposited in the nose and nasopharynx. Smaller particles that pass the upper airway can be deposited in the bronchial region and lower airway. A size-selective deposition model and sampling of particles has been standardized both in Europe and internationally. The... 

Particles are present in outdoor air and are also generated indoors from a large number of sources including tobacco smoking and other combustion processes. Particle size, generally expressed in microns (10-6 m) is important because it influences the location where particles deposit in the respiratory system (U.S. Environmental Protection Agency 1995), the efficiency of particle removal by air filters, and the rate of particle removal from indoor air by deposition on surfaces. 

Tu, K.W. and E.O. Knutson, Total Deposition of Ultrafine Hydrophobic and Hygroscopic Aerosols in the Human Respiratory System, Aerosol Sci. and Technology. 453-465 (1984). 

Another concept relating to the decay products is that of the "unattached" fraction. Although it is now known that the decay product atoms are really attached rapidly to ultrafine particles (0.5 to 3 nm in diameter), there is a long history of an operationally defined quantity called the "unattached" fraction. These decay products have much higher mobilities in the air and can more effectively deposit in the respiratory system. Thus, for a long time the "unattached" fraction has been given extra importance in estimating the health effects of radon decay products. Typically most of the "unattached" activity is Po-218 and the value of unattached frac-... 

The rationale for basing air quality standards on smaller particles is evident from an examination of Fig. 2.12, a diagram of the human respiratory tract. Larger particles that are inhaled are removed in the head or upper respiratory tract. The respiratory system from the nose through the tracheobronchial region is covered with a layer of mucus that is continuously moved upward by the motion of small hairlike projections called cilia. Large particles deposit on the mucus, are moved up, and are ultimately swallowed. 

Figure 2.13 shows the deposition of particles in various regions of the respiratory tract as a function of particle diameter (Phalen, 1984 Phalen et al., 1991 Yeh et al., 1996). The deposition fraction of PM1() in the pulmonary and tracheobronchial regions can be quite large, so it is not surprising that health effects could be associated with these particles. Deposition in the upper portions of the respiratory system is dominated primarily by the large particles, which are readily taken out in the nose and upper airways. 

There are several different types of effective diameters. One of the most commonly used is the aerodynamic diameter, Da, which is defined as the diameter of a sphere of unit density (1 g cm 3) that has the same terminal falling speed in air as the particle under consideration. This effective diameter is particularly useful because it determines the residence time in the air and it reflects the various regions of the respiratory system in which particles of different sizes become deposited. D, is given by Eq. (A) ... 

Larger particles (several micrometers in size) are deposited in the ciliated portion and are cleared from the respiratory system by muco-ciliary action into the gastronomical tract, but may produce systemic toxic effects by absorption in body fluids. Finer particles reach the lower non-ciliated portion of the lungs, are cleared very slowly, and are responsible for diseases such as pneumoconiosis and lung cancer. Metallic lead (Pb), tellurium ( ), selenium (Se), and platinum (Pt) are known to cause both systemic and respiratory toxicity in laboratory animals and several cases of acute and chronic poisoning among metal workers have also been documented. 

Deposition doses in the human respiratory system were estimated based on the roadside PNCs in various locations. These showed the similar trend to the roadside PNCs since the dose estimates did not take into account the size distributions of particles at each site. Average deposition doses over all the considered locations were found to be 3.61 0.17 x 1010 h 1 for male subjects, with exceptionally high values (1.61 0.08 x 1011 h ) for site at Birmingham where the study was carried out along the roadside about 15 years ago (i.e. in 1996-1997). 

To estimate inhalation contact exposure, some assumptions must be made which err on the side of conservatism and which should be modified as more complete data become available. It is necessary to know the droplet size spectrum of the spray because the diameter of the droplet influences its movement down the respiratory system (11). The functional unit of the lung is the alveolus, which is the terminal branch in the system. It is presumed that pesticide particles which are soluble in respiratory tract fluid and are 5p or less in diameter will reach the alveolus where they will be readily absorbed through the cells of the alveolar membrane into the pulmonary capillary beds and hence into the circulatory system. A recent review by Lippmann at al. (12) discusses in depth the deposition, retention and clearance of inhaled particles. 

Mathematical modelling of fine aerosol deposition in the respiratory system. In Deposition and Clearance of Aerosols in the Human Respiratory Tract (ed. W. Hoffmann), pp. 34-40. Salzburg, Facultas. 

Tu, K.W. Knutson, E.O. (1984) Total deposition of ultrafine hydrophobic and hygroscopic aerosols in the human respiratory system. Aerosol Science Technology, 3, 453-65. 

I. Salma, I. Balashazy, R. Winkler-Heil, W. Hofmann, Gy. Zaray, Effect of particle mass size distribution on the deposition of aerosols in the human respiratory system,... 

The methods the USEPA uses in the derivation of inhalation RfDs are similar in concept to those used for oral RfDs however, the actual analysis of initiation exposures is more comple.x tlian oral e. posurcs due to (1) the dynamics of the respiratory system and its diversity across species, and (2) difTcrcnces in the physiochcmical (both physical and chemical) properties of contaminants. Although the identification of the critical study and the determination of the NOAEL in theory are similar for oral and inlralalion e.xposures, several important differences should be noted. In selecting the most appropriate study, the USEPA considers differences in respiratory anatomy and physiology, as well as differences in the physicochemical characteristics of tire contaminant. Differences in respiratory anatomy and physiology may affect the pattern of contaminant deposition in the respiratory tract, and the clearance and redistribution of the agent. Consequently, the different species may not receive the same dose of the contaminant at the same locations within the respiratory tract even though both species were exposed to the same particle or gas concentration. Differences in the physicochemical characteristics of the contaminants, such as the size and shape of a particle or whether the contaminant is an aerosol or a gas, also influence deposition, clearance, and redistribution. 

Particles can also be absorbed from the lungs but their size is a crucial factor. Those that are too big will be removed in the uppermost parts of the respiratory system, while those that are too small will not settle. However, the particles that are deposited in the air sacs may be absorbed into the blood, for example lead from car exhausts. Asbestos fibres that are absorbed into the cells of the lungs are not transferred into the blood, simply staying in situ. Hence they can eventually cause asbestosis and lung cancer. 

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