Bioavailability inhalation

Little is known regarding the pharmacokinetic properties of volatile nitrites in humans, particularly isobutyl nitrite and its primary metabolite, isobutyl alcohol. In rodents, after an intravenous infusion of isobutyl nitrite, blood concentrations peaked rapidly and then declined, with a half-life of 1.4 minutes and blood clearance rate of 2.9 L/min/kg (Kielbasa and Fung 2000). Approximately 98% of isobutyl nitrite is metabolized rapidly to isobutyl alcohol, concentrations of which also decline rapidly, with a half-life of 5.3 minutes. Bioavailability of inhaled isobutyl nitrite at a concentration of 300-900 ppm is estimated to be 43%. 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

Bioavailability from Environmental Media. Endosulfan can be absorbed following inhalation of contaminated workplace air and ingestion of insecticide-contaminated food (Ely et al. 1967). Dermal contact with or ingestion of endosulfan that is tightly bound to soil particles is an exposure route of... 

Bioavailability from Environmental Media. Trichloroethylene can be absorbed following inhalation (Andersen et al. 1980 Astrand and Ovrum 1976 Bartonicek 1962 Dallas et al. 1991 Fernandez et al. 1977 Monster et al. 1976 Muller et al. 1974 Sato and Nakajima 1978), oral (DeFalque 1961 D Souza et al. 

Bioavailability from Environmental Media. The absorption and distribution of americium as a result of inhalation and ingestion exposures have been discussed in Sections 3.3.1 and 3.3.2. EPA lists identical uptake factors for inhaled and ingested americium (and all the other transuranics other than plutonium) regardless of compound solubility, indicating that the knowledge base for americium is not sufficiently developed to quantify the differences that are recognized for most other elements. 

Exposures of Children. Children will be exposed to americium in the same manner as adults in the general population (i. e., ingestion of food and water and inhalation of air). Americium is potentially found at hazardous waste sites at elevated levels. Since children may have oral exposure to soil through hand-to-mouth activity, bioavailability studies of americium in soil via the oral route may be useful to assess the risk of this type of exposure. 

A number of other peptide molecules are currently being explored for delivery via inhalation (6). Very recently, a much smaller peptide (leuprolide, about 9 amino acid residues) has been delivered by metered dose inhaler (MDI) in a characterized fashion to humans (7). This work revealed that about 50% of a dose deposited in the lung could be bioavailable. This value is much greater than those reported for nasal bioavailabilities of this and similar molecules (8). These results, and ours in the rat lung (9), imply that inhalation administration of some peptide and polypeptide molecules is perfectly feasible. 

Exposure and Bioavailability Issues. Primary routes of exposure to lead are via inhalation and ingestion. Lead exposure occurs through inhalation of airborne lead particles with deposition rates in adults of 30%-50% depending on factors such as particle size and ventilation rate (EPA 1986). Once deposited in the lower respiratory tract, lead appears to be almost completely absorbed (Morrow et al. 1980). 

Aniline is lipophilic (pKa of 4.6) and is expected to be rapidly and completely absorbed in the small intestine (Kao et al. 1978). No information on relative bioavailability following inhalation exposure was located, but as indicated by methemoglobin formation during inhalation experiments, systemic absorption by both the inhalation and the percutaneous routes is extensive. Percutaneous absorption of aniline in hairless mice was 4.7% of the nominal applied doses (Susten et al. 1990). 

To protect humans and other mammals, proposed air-quality criteria range from 0.01 to less than 1.0 mg/m3 for metallic nickel and slightly soluble nickel compounds, 0.015-0.5 mg/m3 for water soluble nickel compounds, and 0.005 to 0.7 mg/m3 for nickel carbonyl (Table 6.10). Inhalation of nickel subsulfide concentrations (0.11 to 1.8 mg Ni/m3) near the current threshold limit value of 1 mg Ni/m3 can produce detrimental changes in the respiratory tract of rats after only a few days of exposure (Benson et al. 1995). Additional animal studies are recommended to identify minimally effective inhalation exposure levels for the various nickel compounds (USPHS 1993). Continued monitoring of nickel refining, nickel-cadmium battery manufacture, and nickel powder metallurgy installations is recommended because ambient air levels of bioavailable nickel at these... 

Bioavailability from Environmental Media. Inhalation studies of humans indicate that -hcxane is bioavailable from the atmosphere. Although -hexane in water or soil is likely to undergo transport to the air because of its volatility (although this would not necessarily be the case with -hexanc in groundwater), pharmacokinetic absorption studies using the oral and dermal routes of exposure would help clarify the bioavailability of -hexane from water, soil, plant material, and other environmental media. 

The inhalation route for administering drugs into the pulmonary system for treatment of respiratory diseases eliminates many bioavailability problems such as plasma binding and first-pass metabolism, which are encountered in parenteral or oral administration. Consequently, a small inhalation dose is adequate for achieving... 

Studies investigating the bioavailability of P.Y.17 in rats, applied not only orally but also by inhalation, in no case showed the presence of any cleavage product of the pigment (e.g., 3,3-dichlorobenzidine or metabolites) in the urine or blood of the animals [31]. Similar studies were carried out with P.Y.13 and 174 [32], Recently the non-bioavailability of 3,3 -dichlorobenzidine from P.Y.13 and P.Y.17 was confirmed by means of molecular dosimetry for hemoglobin and DNA adducts [33]. 

Bioavailability from Environmental Media. Absorption of endrin following inhalation has been shown to occur in laboratory animals (Treon et al. 1955) and endrin can also be absorbed by humans following inhalation of contaminated air (Hoogendam et al. 1965). Since endrin has a low volatility, inhalation is probably not a major concern except for potential inhalation of contaminated dust at hazardous waste sites. 

Bioavailability. Cyanide is known to be absorbed following inhalation, oral, and dermal contact (Gosselin et al. 1976 Rieders 1971). The environmental factors that may influence the bioavailability of cyanide from contaminated air, water, soil, or plant material have not been studied. Since cyanides are not strongly sorbed to soil and sediments (Callahan et al. 1979), the role of sorption may not be significant in determining the bioavailability of cyanides from different soils or waters. The bioavailability of cyanide from an environmental medium is expected to increase if the cyanide is present in water-soluble forms,... 

Bioavailability from Environmental Media. No information was found regarding the absorption of di- -octylphthalate by humans or laboratory animals following inhalation or dermal exposures. No information is available about absorption following oral exposure in humans. However, indirect evidence from animal studies suggests that the compound is readily absorbed by this route (Albro and Moore 1974 Oishi 1990). Additional information is needed on the absorption of di- -octylphthalate as a result of inhalation of contaminated air, ingestion of contaminated food and water, and dermal contact with contaminated soils and sediments. 

The toxicokinetics of disulfoton in humans and animals depends on its physicochemical characteristics and its metabolism. The lipophilicity of disulfoton indicates that the insecticide should be easily absorbed by oral, inhalation, and dermal routes. No bioavailability data were located for inhalation and dermal exposure. However, disulfoton is almost completely absorbed from the gastrointestinal tract within 2 days after oral exposure. Animal studies suggest that disulfoton is widely distributed primarily to the liver and in smaller quantities to the kidney, fat, skin, muscle, brain, and other organs. Disulfoton and/or its metabolites are excreted mainly in the urine of humans and animals, with minor amounts excreted in the feces and expired air. 

Bioavailability from Environmental Media. Available information regarding the rate of disulfoton absorption following inhalation, oral, or dermal contact has been discussed in the Toxicokinetics section (see Section 2.3). Although no data on disulfoton s bioavailability from contaminated air are available, the bioavailability from inhalation exposure is expected to be high because disulfoton is likely to be present in the vapor phase (Eisenreich et al. 1981) and not in the particulate phase in the adsorbed state. Similarly, no data on the bioavailability of disulfoton from water and soil or plant material are available however, disulfoton adsorbs rather strongly to soil (Harris 1969 Helling et al. 1974 Wauchope et al. 1992). Since the part that remains adsorbed to soil or sediments may, at most, be partially bioavailable, disulfoton is expected to have reduced bioavailability from soil and water. Data on the bioavailability of disulfoton from actual environmental media need further development. 

The bioavailability of contaminants to wildlife and humans is also an area of critical importance, where contaminants can be taken up in pore water and by dermal contact, particle ingestion, or particle inhalation. The dynamics of sorption/desorption are not currently incorporated into exposure and risk assessment models for organic compounds, where availability, in most cases, is assumed to be 100% [224]. Recently, the following have been demonstrated and reported ... 

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