Acute release, model selection

For acute releases, the fault tree analysis is a convenient tool for organizing the quantitative data needed for model selection and implementation. The fault tree represents a heirarchy of events that precede the release of concern. This heirarchy grows like the branches of a tree as we track back through one cause built upon another (hence the name, "fault tree"). Each level of the tree identifies each antecedent event, and the branches are characterized by probabilities attached to each causal link in the sequence. The model appiications are needed to describe the environmental consequences of each type of impulsive release of pollutants. Thus, combining the probability of each event with its quantitative consequences supplied by the model, one is led to the expected value of ambient concentrations in the environment. This distribution, in turn, can be used to generate a profile of exposure and risk. 

The monofunctional tryptase inhibitor APC-366 (Axys Pharmaceuticals) reduces the acute airway response and histamine release to allergen in a pig model of allergen-induced asthma [19]. APC-366 is also effective in a sheep model of allergen-induced asthma but was only poorly effective in asthma patients (proof-of-principle) [8], The compound was in clinical development phase II for asthma (inhalative). Although highly selective for tryptase over plasmin and plasma kal-likrein, APC-366 was not selective against thrombin and trypsin [13], Another monofunctional tryptase inhibitor is bis(5-amidino-2-benzimidazol-yl)methane (BABIM) which has been shown to be effective in the sheep. Further development of the compound was, however, discontinued, maybe because of the lack of selectivity over trypsin [13, 16, 17] (Figure 3.2.2). 

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