Inhalation performance specifications

Another in vivo study with a negative result was performed by Simon et al. (58). After administration of (14C) vinyl acetate to male and female rats, either orally or by inhalation, no specific hepatic DNA adducts, known to occur after administration of labelled vinyl halides or vinyl carbamates, could be observed in liver. 

The most common contaminants in produced gas are carbon dioxide (COj) and hydrogen sulphide (HjS). Both can combine with free water to cause corrosion and H2S is extremely toxic even in very small amounts (less than 0.01% volume can be fatal if inhaled). Because of the equipment required, extraction is performed onshore whenever possible, and providing gas is dehydrated, most pipeline corrosion problems can be avoided. However, if third party pipelines are used it may be necessary to perform some extraction on site prior to evacuation to meet pipeline owner specifications. Extraction of CO2 and H2S is normally performed by absorption in contact towers like those used for dehydration, though other solvents are used instead of glycol. 

For supply inlets in rooms some performance measurements exist, such as air exchange and ventilation efficiencies (see Chapter 8). It is usually not possible to use these for local ventilation supply inlets, and for the moment there are no specific measurements to evaluate the influence of an inlet on contaminants. Some trials with comparison indices, which compare inhaled concentrations (or exposures) with and without a supply inlet, have been done. 

Studies have shown that in order to clear the oropharyngeal impaction barrier (comprising the mouth, throat, and pharynx), particles with aerodynamic diameters smaller than 5 pm are required [3,4]. Only particles with aerodynamic diameters less than 3 pm reach the terminal bronchi and the alveoli in significant numbers [5]. Therefore, the particle diameter required to be produced by the delivery system depends to a great extent on the intended target lung tissue. Lung deposition is also affected substantially by the specific inhalation dynamics of the patient, which in turn are influenced by the delivery device. This article addresses various attributes of the dry powder inhalation product, from intrinsic material properties to final product performance. 

The TGD has noted that in practice, relevant data on kinetics and metabolism, especially after dermal and inhalation exposure, are frequently missing. As a consequence, corrections can only be made for differences in bioavailability. There are some pragmatic approaches in order to calculate a NAEL (or LAEL) by extrapolation, when specific data are not available. The methods described are for extrapolating from oral toxicity data since this is the route most often used for repeated dose toxicity studies in animals. The TGD emphasized that it should be noted that insight into the reliability of the current methodologies for route-to-route extrapolation has not been obtained yet, with a reference to the smdy performed by WUschut et al. (1998), see above. 

Exposure assessments characterize the water, diet, and herbicide handling exposure pathways for atrazine and simazine (Sielken et al, 1996, 1998). For each exposure pathway, the chemical-specific doses (mg/kg/day) from each relevant route (ingestion, inhalation, and dermal) are summed. The total chemical-specific dose for each exposure pathway is characterized separately, and then these doses are aggregated by summing over the multiple exposure pathways. The pathway-specific and aggregate assessments are performed separately for atrazine and simazine. In addition, because atrazine and simazine are assumed to have a common mechanism of toxicity, a cumulative exposure assessment is performed combining the doses of atrazine and simazine. 

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