Inhalation routes concept

Pulmonary delivery currently represents the most promising alternative to parenteral delivery systems for biopharmaceuticals. Delivery via the pulmonary route moved from concept to reality in 2006 with the approval of Exubera, an inhalable insulin product (Chapter 11). Although the lung is not particularly permeable to solutes of low molecular mass (e.g. sucrose or urea), macromolecules can be absorbed into the blood via the lungs surprisingly well. In fact, pulmonary... 

Because the mucus layer or the underlying cells may serve as either final accumulation sites of toxic gases or layers through which the gases diffuse en route to the blood, we need simplified models of these layers. Altshuler et al. have developed for these layers the only available model that can be used in a comprehensive system for calculating tissue doses of inhaled irritants. It assumes that the basement membrane of the tracheobronchial region is covered with three discrete layers an inner layer of variable thickness that contains the basal, goblet, and ciliated cells a 7-Mm middle layer composed of waterlike or serous fluid and a 7-Mm outer layer of viscous mucus. Recent work by E. S. Boatman and D. Luchtel (personal communication) in rabbits supports the concept of a continuous fluid layer however, airways smaller than 1 mm in diameter do not show separate mucus and serous-fluid layers. 

Exposures to solvents occur throughout life from conception to death. Solvent vapors inhaled by the mother often reach the fetus. The elderly often spend their last days in the hospital where the odor of the solvents, disinfectants often prevails. Exposures also occur in the course of daily living. Exposures may range from the inhalation of vapors from a newspaper freshly off the news stand, to the intake of the cleaning solvent by all routes of exposure being used. Effects from the exposure may range from simple objection to a low concentration odor, to death at high concentrations. In between, there is a whole spectrum of effects. 

The basic concept is that estimated results for pesticide movements and exposure levels vary greatly with the model types and modeling philosophy. Before con-dncting a model exercise, a conceptual check of the model is needed to ascertain if the model contains aU relevant routes of exposure. A simple model, such as SCIES, is based on worst-case assumptions, and may be sufficient for inhalation risk assessment. More complicated simulation models, such as CONSEXPO and InPest, provide information on the amounts of pesticides on the room materials, as well as the airborne concentration, and they are appropriate for risk assessment via aU routes. Even in complicated models, each mechanistic model contains assumptions to simplify the process description of the pesticide movement in the real world . The underlying assumptions for each of the models, and the relevant processes they implicate, are criteria to consider when selecting an appropriate model. Therefore, the validity of the assumptions used for the assessment should be considered before using the model, and they should be well documented. A simple phrase such as, we used model xx to estimate an exposure level of yy, is inadequate for documentation purposes. 

Further, different routes of exposure such as dermal, or inhalation exposure are of much more importance than exposure via the oral route. Thus, the old concept of minimal toxicity data for pesticides which do not leave residues in food is being abandoned. 

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