Inhaled bolus

C Heyder, J. Stahlhofen, W. Regional deposition and retention of particles in the shallow, inhaled boluses effect of lung volume. J. Appl. Physiol. 1999, 86 (1), 168-179. 

Almost all inhaled chlorine (>90%) is absorbed via the respiratory tract, in both humans and animals (Abdel-Rahman et ah, 1983 Nodelman and Ultman, 1999a,b Morris et al., 2005). Humans absorbed >95% of an inhaled bolus of 0.5-3 ppm chlorine in the upper airway and <5% in the lower airway, regardless of the mode of breathing or respiratory flow rate (Nodelman and Ultman, 1999a,b). Chlorine that is absorbed is not subject to metabolic biotransformation and is distributed widely throughout the body and joins the pool of chloride ions. Rats that were orally administered HO Cl in distilled water excreted the majority of C1 in the urine (36.43%) and feces (14.80%) over a 96h post-exposure period (Abdel-Rahman et al., 1983). 

No animal or human data were available for inhalation exposure. There are no data regarding effects in humans after oral exposure. Information is available in animals regarding health effects following acute, intermediate, and chronic oral ingestion of diisopropyl methylphosphonate. The animal data obtained after oral exposure indicate that diisopropyl methylphosphonate is moderately toxic after acute bolus exposure but has a lower order of toxicity after intermediate and chronic exposures in food. No data were found on the toxicity of diisopropyl methylphosphonate after exposure in drinking water. Further, diisopropyl methylphosphonate is rapidly metabolized and excreted and does not accumulate. It does not appear to have reproductive or developmental effects. At the doses tested, it does not appear to be an acetylcholinesterase inhibitor, although this issue has not been resolved yet. Limited data are available for dermal exposure in humans and animals. Diisopropyl methylphosphonate does not appear to be a... 

The second part describes different experimental approaches to simultaneously assess deposition and subsequent absorption of pharmaceutical aerosol formulations, typically by adapting some existing impactor/impinger devices to accommodate pulmonary epithelial cell culture systems. Differences between longtime and low-dose aerosol deposition in environmental toxicology and short time bolus inhalation of pharmaceutical aerosols are elucidated. 

Whipple, Chen, and Wang S showed that the distribution of an inhaled aerosol bolus depends on the orientation of the successive airway bifurcations and the volume of the bolus. On the basis of skewed velocity profiles, they made theoretical calculations of the distribution of aerosol boli in branching airways that were in fair agreement with the experimental data. Their results suggested that slow and shallow breaths should show greater differences in dispersion of irritant gases in the airways. 

New techniques have been developed for the direct measurement of mucociliary transport rates in the trachea. Yeates et al. used an external gamma camera to follow a bolus of labeled microspheres deposited in the large airways by aerosol inhalation they fitted a log-normal distri-... 

Skyler JS, Weinstock RS, Pasdn P, Yale JF, Barrett E, Gerich JE, Gerstein HC (2005) Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects A 16-month randomized, comparative trial. Diab Care 28(7) 1630-1635... 

If salvinorin is inhaled as multiple inhalations of leaf smoke or vapor one could reasonably expect to pass out before he/she could take a lethal overdose. But significantly, nothing is known about the toxic effects of smoking truly massive single bolus doses of pure salvinorin, such a practice might be quite dangerous, and should certainly be avoided. 

The distinction in clearance kinetics from the NP and P regions, illustrated in Fig. 7.3, has however been challenged by Stahlhofen etal. (1986). These authors arranged for subjects to inhale Fe203 particles, labelled with 198Au, in a bolus of air of defined volume. The bolus was... 

Geller, D., Thipphawong, J., Otulana, B., et al. (2003), Bolus inhalation of rhDNase with the AERx system in subjects with cystic fibrosis,/. Aerosol Med., 16,175-182. 

For example, the range of concentrations in 36 digests of fetal tissues sacrificed 1 hour after injection in the mouse experiment ranged from 116 to 30,342 fig (Haque and Vrazel 1998). This variability may due to an inconsistent mass breakthrough of fibers associated with the bolus intravenous administration (Cunningham and Pontefract 1974). It is expected that the extent of transplacental transfer of fibers would be much less with inhalation, oral, or dermal exposures. 

These data were quite variable, and thus could be due, at least in part, to a mass breakthrough of fibers that might be associated with the bolus intravenous exposure protocol. It is expected that transplacental transfer of fibers following environmental exposures (inhalation, oral, or dermal) to asbestos may be of a much smaller magnitude. 

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