Pulmonary excretion

Pulmonary excretion takes place for volatile compounds. Alveolar air is at equilibrium with capillary blood. Thus, pulmonary excretion depends on the vapor pressure of the compound and its blood solubility. If blood solubility is... 

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). 

No clinical treatments other than supportive measures are currently available to enhance elimination of trichloroethylene following exposure. Studies designed to assess the potential risks or benefits of increasing ventilation to enhance pulmonary elimination or of stimulating excretion of trichloroethylene and its decomposition products are needed. 

Susman JL, Homig JF, Thomae SC, et al. 1978. Pulmonary excretion of hydrogen sulfide, methanethiol, dimethyl sulfide and dimethyl disulfide in mice. Drug Chem Toxicol 1 327-338. 

The internal dose of propoxur was measured by assessing the total amount of 2-isopropoxyphenol (IPP) excreted in the urine, collected over a period of 24 hr from the start of exposure, and described in detail in previous studies (Brouwer et al., 1993 Meuling et al., 1991). Volunteer kinetics studies revealed a one-to-one relationship of absorbed propoxur and excreted IPP on a mole basis. Based on the results by Machemer et al. (1982), a pulmonary retention of 40% was used to calculate the relative contribution of the respiratory exposure to the internal exposure. To estimate the contribution of the dermal exposure, the calculated respiratory portion was subtracted from the total amount of IPP excreted in urine. 

Bolus diuretic administration decreases preload by functional venodilation within 5 to 15 minutes and later (>20 min) via sodium and water excretion, thereby improving pulmonary congestion. However, acute reductions in venous return may severely compromise effective preload in patients with significant diastolic dysfunction or intravascular depletion. 

None of the exposures produced changes in clinical chemistry values (blood count, blood nitrate, blood urea nitrogen, serum enzymes, and serum electrolytes or urinalysis and nitrate and nitrite urinary excretion), spontaneous electrical activity of the cortex of the brain (detected by EEG), pulse rate and sinus rhythm, or pulmonary function. Visual and auditory acuity, exercise EKG, and time estimation tests did not differ from control values for any of the exposures. Only one of several cognitive tests was affected by exposure and the change occurred only in the four subjects exposed at 1.5 ppm. The test was taken during the time the subjects were experiencing severe headaches. 

Expired Air. Volatile compounds or metabolites can be extensively excreted by passage across pulmonary membranes into the airspace of the lungs, then by expulsion from the lungs in expired air. 

Kidney Failure The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH]... 

Potentially, individuals with low activities of the enzymes phenol sulfotransferase and glucuronyl-transferase may be more susceptible to phenol toxicity. Persons with ulcerative colitis may have an impaired capacity to sulfate phenol (Ramakrishna et al. 1991), which may increase the amount of unchanged phenol that is absorbed following oral exposure. Neonates may also be more susceptible to toxicity from dermally-applied phenol because of increased skin permeability and proportionately greater surface area. A study in which 10-day-old rats were more sensitive to lethality following oral exposure to phenol than 5-week-old or adult rats (Deichmann and Witherup 1944) further suggests that the young may be more sensitive to phenol. (For a more detailed discussion please see Section 2.6.) Because phenol is a vesicant, individuals with sensitive skin or pulmonary incapacity may be more sensitive to phenol. Individuals with kidney or liver diseases that impair metabolism or excretion of phenol and phenol metabolites may be more susceptible to phenol. 

Excretion is the process of eliminating drugs from the body. They may be excreted as metabolites or as unchanged drug. As mentioned above, compounds that are polar and water soluble are more readily eliminated. The major routes of excretion are renal, biliary/fecal, lactational, and pulmonary. 

According to dermal absorption studies with solvents other than chloroform, the absorption of such solvents in guinea pigs is more rapid than the metabolism or pulmonary excretion (Jakobson et al. 1982). 

Following a single, oral exposure, most of the 0.5 grams of radioactively labeled chloroform administered to volunteers was exhaled during the first 8 hours after exposure (Fry et al. 1972). A slower rate of pulmonary excretion was observed during the first eight hours in volunteers who had more adipose tissue than the other volunteers. Up to 68.3% of the dose was excreted unchanged, and up to 50.6% was excreted as carbon dioxide. A positive correlation was made between pulmonary excretion and blood concentration. Less than 1% of the radioactivity was detected in the urine. 

The excretion of chloroform and its metabolites is understood, based on human and animal data derived from oral and inhalation studies (Brown et al. 1974a Corley et al. 1990 Fry et al. 1972 Taylor et al. 1974). The major route of chloroform elimination is pulmonary, but minor pathways are through enterohepatic circulation, urine, and feces as parent compound or metabolites. There are no human or animal data regarding excretion of dermally applied chloroform. 

Any volatile material, irrespective of its route of administration, has the potential for pulmonary excretion. Certainly, gases and other volatile substances that enter the body primarily through the respiratory tract can be expected to be excreted by this route. No specialized transport systems are involved in the loss of substances in expired air simple diffusion across cell membranes is predominant. The rate of loss of gases is not constant it depends on the rate of respiration and pulmonary blood flow. 

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