Uptake inhalation

Gargas ML, Clewell HJ, Andersen ME. 1990. Gas uptake inhalation techniques and the rates of metabolism of chloromethanes, chloroethanes and chloroethylenes in the rat. Inhalation Toxicology 2 295-319. 

Gontrol values for relevant elements in soils regarding the pathways effecting human being (directly contact by oral uptake, inhalation or skin contact) are detailed in Table 1.21. 

Fuxe K, Andersson K, Nilsen OG, et al Toluene and telencephalic dopamine selective reduction of amine mrnover in discrete DA nerve terminal systems of the anterior caudate nucleus by low concentrations of toluene. Toxicol Lett 12 115—123,1982 Cause EM, Mendez V, Geller I Exploratory smdies of a rodent model for inhalant abuse. Neurobehav Toxicol Teratol 7 143—148, 1985 Gentry JR, Hill C, Malcolm R New anticonvulsants a review of applications for the management of substance abuse disorders. Ann Clin Psychiatry 14 233—245, 2002 Gerasimov MR, Ferrieri RA, Schiffer WK, et al Smdy of brain uptake and biodistribution of [llCjtoluene in non-human primates and mice. Life Sci 70 2811 — 2828, 2002... 

Asphyxiants interfere with the body s oxygen uptake mechanisms. Air normally contains 21% oxygen. Oxygen deficiency in inhaled air, e.g. due to the presence of nitrogen, argon, or carbon dioxide in a confined space, depending on the concentration and duration, may affect the body and ultimately cause death from simple anoxia (Table 4.7). 

Absorption of trichloroethylene in humans is very rapid upon inhalation exposure. Trichloroethylene has a blood/gas partition coefficient that is comparable to some other anesthetic gases (i.e., chloroform, diethylether, and methoxyfluorene), but it is much more lipophilic than these gases. As a consequence of these properties, the initial rate of uptake of inhaled trichloroethylene in humans is quite high, with the rate leveling off after a few hours of exposure (Fernandez et al. 1977). The absorbed dose is proportional to the inhaled trichloroethylene concentration, duration of exposure, and alveolar ventilation rate at a given inhaled air concentration (Astrand and Ovrum 1976). Several studies indicate that 37-64% of inhaled trichloroethylene is taken up from the lungs (Astrand and Ovrum 1976 Bartonicek 1962 Monster et al. 1976). 

Dekant et al. 1986b Filser and Bolt 1979 Prout et al. 1985). Male mice can metabolize inhaled trichloroethylene to a greater extent than male rats (Stott et al. 1982). In this study, virtually 100% of the net trichloroethylene uptake by mice was metabolized at both 10- and 600-ppm exposure concentrations, and there was no evidence of metabolic saturation. In rats, however, 98% of the net trichloroethylene uptake from the 10-ppm exposure was metabolized, but only 79% was metabolized at the 600-ppm exposure level. This suggested an incremental approach to the saturation of metabolism in this exposure range in the rat. Rats exposed by inhalation to trichloroethylene concentrations of 50 or 500 ppm for 2 hours showed metabolic saturation at 500 ppm (Dallas et al. 1991). This was indicated by the fact that the trichloroethylene blood levels of the 500-ppm animals progressively increased over the 2-hour period, rather than approaching equilibrium after 25 minutes, as was the case at 50 ppm. 

PBPK models have also been used to explain the rate of excretion of inhaled trichloroethylene and its major metabolites (Bogen 1988 Fisher et al. 1989, 1990, 1991 Ikeda et al. 1972 Ramsey and Anderson 1984 Sato et al. 1977). One model was based on the results of trichloroethylene inhalation studies using volunteers who inhaled 100 ppm trichloroethylene for 4 horns (Sato et al. 1977). The model used first-order kinetics to describe the major metabolic pathways for trichloroethylene in vessel-rich tissues (brain, liver, kidney), low perfused muscle tissue, and poorly perfused fat tissue and assumed that the compartments were at equilibrium. A value of 104 L/hour for whole-body metabolic clearance of trichloroethylene was predicted. Another PBPK model was developed to fit human metabolism data to urinary metabolites measured in chronically exposed workers (Bogen 1988). This model assumed that pulmonary uptake is continuous, so that the alveolar concentration is in equilibrium with that in the blood and all tissue compartments, and was an expansion of a model developed to predict the behavior of styrene (another volatile organic compound) in four tissue groups (Ramsey and Andersen 1984). 

Andersen ME, Gargas ML, Jones RA, et al. 1980. Determination of the kinetic constants for metabolism of inhaled toxicants in vivo using gas uptake measurements. Toxicol Appl Pharmacol 54 100-116. 

Besides the inhalative use, the development of a drug formulation for A9-THC has to address other bioavailabihty questions. A major problem is the hpophiUcity and poor solubiUty in water, hmiting oral uptake when given orally. Because of this, other parenteral routes of apphcation are imder investigation like puhnonal uptake by vaporization, subUngual or intranasal administration, and apphcation by injection of A9-THC incorporated in hpo-somes. 

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. 

Absorbed Dose, Chemical—The amount of a substance that is either absorbed into the body or placed in contact with the skin. For oral or inhalation routes, this is normally the product of the intake quantity and the uptake fraction divided by the body weight and, if appropriate, the time, expressed as mg/kg for a single intake or mg/kg/day for multiple intakes. For dermal exposure, this is the amount of material applied to the skin, and is normally divided by the body mass and expressed as mg/kg. 

Interroute extrapolation. The IEUBK Model includes an exposure module that simulates age-specific lead exposures via inhalation, and ingestion of lead in diet, dust, lead-based paint, soil, and water. The total exposure from each route is defined as the total lead uptake ( pg/day) over a 1-month period. Other routes of exposure may be simulated by the IEUBK Model pending available information from which to characterize both the exposure and media-specific absorption variables. Values for variables in the biokinetic component of the IEUBK Model are independent of the route of exposure. 

Booker DV, Chamberlain AC, Newton D, et al. 1969. Uptake of radioactive lead following inhalation and injection. Br J Radiol 42 457-466. 

Fig. 2b. Bone and liver uptake of inhaled cerium in Class D, W and Y compounds (no radioactive decay) as projected from the TGLD model coupled with the ICRP committee II model for radiocerium,...

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