Human Respiratory Tract Physiology

Industrial environments expose individuals to a plethora of airborne chemical compounds in the form of vapors, aerosols, or biphasic mixtures of both. These atmospheric contaminants primarily interface with two body surfaces the respiratory tract and the skin. Between these two routes of systemic exposure to airborne chemicals (inhalation and transdermal absorption) the respiratory tract has the larger surface area and a much greater percentage of this surface exposed to the ambient environment. Or dinary work clothing generally restricts skin exposures to the arms, neck, and head, and special protective clothing ensembles further limit or totally eliminate skin exposures, but breathing exposes much of the airway to contaminants. 

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Lippmann, M. (1977). Regional deposition of particles in the human respiratory tract , Section 9, page 213 in HANDBOOK OF PHYSIOLOGY, Lee, H. D. K. Sect. Ed., (American Physiological Society, Bethesda, Md.). 

Since the human respiratory tract is anatomically and physiologically a very heterogeneous system, the rate and extent of absorption of macromolecules as well as their potential adverse reactions depend on the regional doses. The most convenient method to deliver drugs to the respiratory tract is by inhalation. Other methods of delivery such as intratracheal instillation are used in experimental settings but are generally unsuitable for real-life therapeutic products. This section... 

Lung cell cultures can provide mechanistic insights but they do not represent the complexity in the delivery and disposition of drugs in the human respiratory tract. Perfused lung organ studies provide the next level in complexity. Various animal models have been used with the view to predict quantitatively absorption of peptides and proteins from the human lungs. However, due to the major differences in the anatomy and physiology of respiration in primates, the predictive power of these models is quite limited as evidenced by the data in Fig. 2. (Animal models are, of course, essential in the assessment of safety and they can provide valuable mechanistic information.)... 

Figure 12. Two ventilatory states, i.e. 750 ml and 2150 ml tidal volume ( 11 and 32 1 min volumes, respectively), are used to indicate the order and direction of change in compartmental deposition which are induced by such physiological factors. Note the crossover in the P curves at approximately 0.8 pm diameter (AMAD). Reproduced with permission from Task Group on Lung Dynamics (1966). Deposition and retention models for internal dosimetry of the human respiratory tract. Health Physics, 12, 173-207. Lippincott, Williams Wilkins...

Roy M, Becquemin H-H, Bertholon J-F, et al. 1994. Respiratory physiology. In Human respiratory tract model for radiological protection. ICRP Publication 66. International Commission on Radiological Protection. Pergamon Press, Oxford. 167-201. 

Heyder J, Blanchard JD, Feldman HA, Brain JD. Convective mixing in human respiratory tract estimates with aerosol boli. J Appl Physiol 1988 64 1273-1278. Paiva M, Engel L. Gas mixing in the lung periphery. In Chang HK, Paiva M, eds. Respiratory Physiology. An Analytical Approach. New York Marcel Dekker,... 

The toxic action of bromine is similar to that of chlorine and can cause physiological damage to humans through inhalation and oral routes. It is an irritant to the mucous membranes of the eyes and upper respiratory tract. Severe exposures may result in pulmonary edema. Chronic exposure is similar to therapeutic ingestion of excessive bromides. 

The largest number of studies of the toxicity of acrolein in animals was conducted by way of inhalation, probably because acrolein has an appreciable vapor pressure under ambient conditions and inhalation is the principal exposure for humans (Beauchamp et al. 1985). Because of their intolerance to sharp and offensive odor and to intense irritation of conjunctiva and upper respiratory tract, humans have not suffered serious intoxication from acrolein. The strong lacrimatory effect of acrolein is usually a warning to occupational workers. Physiological perception of acrolein by humans begins at about 500 to 1000 pg/L air with eye and nasal irritation. The irritating effects compel afflicted individuals to immediately leave the polluted area (Beauchamp etal. 1985). Laboratory animals died from inhalation of 8000 to 11,000 pg/L after 4 to 6 h, mice from 875,000 pg/L after 1 min, and rats from 660 pg/L for 24 days (Table 10.4). Animals dying from... 

First, the procedure now used by the EPA for inhalation data differs from what we have described above, in that the ten-fold factor for interspecies extrapolation (animal-to-human) is dropped in favor of a specific model that describes the well-known physiological differences between animals and humans that affect the relative rates of movement of a given administered dose of a chemical in the respiratory tracts of animals and humans. These physiological models provide fairly accurate predictions of the relative doses of chemicals delivered into the respiratory regions of animals and humans who have received identical administered (inhaled) doses. The estimate of delivered dose offers a well-accepted scientific approach to at least part of the problem of interspecies differences. Details of the delivered dose calculations are beyond the scope of this book (see references in Sources and recommended reading). 

For substances with local effects on the respiratory tract, no general approach for interspecies scaling can be given. Anatomical and physiological differences in the airways between experimental animals and humans contribute to interspecies differences in local effects observed between animals and humans, see Section 4.7.8. It should be noted, however, that for local effects the determining factor for effects to occur in the respiratory tract is generally the concentration of the chemical in the air rather than the total dose and thus allometric scaling is not relevant. 

Anatomy and physiology. The human respiratory system is divided into upper and lower respiratory tracts. The upper respiratory system consists of the nose, nasal cavities, nasopharynx, and oropharynx. The lower respiratory tract consists of the larynx, trachea, bronchi, and alveoli, which are composed of respiratory tissues. 

Hydrogen chloride is not nearly as toxic as HF, although inhalation can cause spasms of the larynx as well as pulmonary edema and even death at high levels. Because of its high affinity for water, HC1 vapor tends to dehydrate tissue of the eyes and respiratory tract. Hydrochloric acid is a natural physiological fluid found as a dilute solution in the stomachs of humans and other animals. 

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