Excretion exhalation

Humans eliminate ingested 1,1,1-trichloroethane in their exhaled breath (Stewart and Andrews 1966), but no studies were located that quantified excretion rates or the extent of excretion. The pattern of elimination is expected to be similar to that of inhaled 1,1,1-trichloroethane (i.e., exhalation of unchanged 1,1,1 -trichloroethane should be the predominant route of excretion exhalation of CO2 and urinary excretion of other metabolites are minor routes). This pattern has been observed in animals after inhalation (see Section 2.3.4.1) and oral exposure (Mitoma et al. 1985 Reitz et al. 

The kinetic properties of chemical compounds include their absorption and distribution in the body, theit biotransformation to more soluble forms through metabolic processes in the liver and other metabolic organs, and the excretion of the metabolites in the urine, the bile, the exhaled air, and in the saliva. An important issue in toxicokinetics deals with the formation of reactive toxic intermediates during phase I metabolic reactions (see. Section 5.3.3). 

The rate of elimination of a chemical compound from the body is usually proportional to the amount of the chemical in the body. Elimination processes include biotransformation, exhalation, and excretion in the urine, bile, saliva, and sweat, and even in the hair and nails. The first-order... 

Alcohol sulfates are easily metabolized by mammals and fishes either by oral or intraperitoneal and intravenous administration. Several labeled 35S and 14C alcohol sulfates have been used to determine their metabolism in experiments with rats [336-340], dogs [339], swines [341], goldfish [342], and humans [339]. From all of these studies it can be concluded that alcohol sulfates are absorbed in the intestine of mammals and readily metabolized by to and p oxidation of the alkyl chain and excreted in the urine and feces, but are also partially exhaled as carbon dioxide. Fishes absorb alcohol sulfates through their gills and metabolize them in a similar way to that of mammals. 

The body maintains blood pH by two primary mechanisms respiration and excretion. Carbonic acid concentration is controlled by respiration as we exhale, we deplete our system of CO, and hence deplete it of H2C03, too. This decrease in acid concentration raises the blood pH. Breathing faster and more deeply increases the amount of C02 exhaled and hence decreases the carbonic acid concentration in the blood, which in turn raises the blood pH. Hydrogen carbonate ion concentration is controlled by its rate of excretion in urine. 

Respiratory acidosis results when decreased respiration raises the concentration of C02 in the blood. Asthma, pneumonia, emphysema, or inhaling smoke can all cause respiratory acidosis. So can any condition that reduces a person s ability to breathe. Respiratory acidosis is usually treated with a mechanical ventilator, to assist the victim s breathing. The improved exhalation increases the excretion of C02 and raises blood pH. In many cases of asthma, chemicals can facilitate respiration by opening constricted bronchial passages. 

Note This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Following inhalation exposure to trichloroethylene in humans, the unmetabolized parent compound is exhaled, whereas its metabolites are primarily eliminated in the urine. Excretion of trichloroethylene in the bile apparently represents a minor pathway of elimination. Balance studies in humans have shown that following single or sequential daily exposures of 50-380 ppm trichloroethylene, 11% and 2% of the dose was eliminated unchanged and as trichloroethanol, respectively, in the lungs 58% was eliminated as urinary metabolites and approximately 30% was unaccounted for (Monster et al. 1976, 1979). Exhaled air contained notable concentrations of trichloroethylene 18 hours after exposure ended because of the relatively long half-life for elimination of trichloroethylene from the adipose tissue (i.e., 3.5-5 hours) compared to other tissues (Fernandez et al. 1977 Monster et al. 1979). 

Excretion data show that saturability of trichloroethylene metabolism occurs at lower exposure levels for rats than for mice (Dekant et al. 1986b Prout et al. 1985). In mice receiving a single oral dose of 10, 500, 1,000, or 2,000 mg/kg trichloroethylene, urinary TCA and exhaled carbon dioxide over a 24-hour period were... 

Differences among individuals can partially explain the differences in the before workshift and end of workshift levels of trichloroethylene and its metabolites. Increased respiration rate during a workday, induced by physical workload, has been shown to affect levels of unchanged trichloroethylene more than its metabolites, while the amount of body fat influences the levels of the solvent and its metabolites in breath, blood, and urine samples before workshift exposure (Sato 1993). Additionally, liver function affects measurements of exhaled solvent at the end of workshift increased metabolism of trichloroethylene will tend to decrease the amount exhaled after a workshift. Increased renal function would affect levels of TCA and trichloroethanol in blood before a workshift in the same way, but it probably would not affect urine values between the begiiming and the end of the workshift because of the slow excretion rate of TCA. 

Trichloroethylene is exhaled following inhalation and oral exposures (Dallas et al. 1991 Koizumi et al. 1986 Stewart et al. 1970), whereas metabolites are mainly excreted in the urine (Fernandez et al. 1977 Koizumi et al. 1986 Monster etal. 1979 Sato et al. 1977). Based on the knowledge of trichloroethylene metabolism and excretion, potential methods for reducing the body burden are presented. These methods have not been used in persons or animals exposed to trichloroethylene and should be researched further before being applied. 

Forssman S, Holmquist CE. 1953. The relation between inhaled and exhaled trichloroethylene and trichloroacetic acid excreted in the urine of rats exposed to trichloroethylene. Acta Pharmacol Toxicol 9 235-244. 

Metabolism of NHEX- C in the rat results in dose dependent formation of C02> with 45% exhaled after a dose of 8 mg/kg NHEX but only 4% after 576 mg/kg (17). Similar results were obtained for NPYR and nitrosoheptamethyleneimine. At doses of 8-12 mg/kg NHEX, 33-37% of the radioactivity was excreted in the urine (17, 52). Urinary metabolites of NHEX were e-caprolactam, e-amino-caproic acid, and 6-aminocaprohydroxamic acid (52). The formation of 6-caprolactam is analogous to results with NPYR and NNN, in which 2-pyrrolidinone and norcotinine were observed as urinary metabolites. Caprolactam did not originate from hexamethylene-imine, a product of denitrosation. 

Male rats given single, oral doses of 14 mg/kg [l-14C]tributyl phosphate excreted 50% of the label in urine, 10% in exhaled air as C02, and 6% in the feces within 1 day (Suzuki et al. 1984a). Within 5 days, cumulative radioactivity in urine, exhaled C02, and feces accounted for approximately 68%, 10%, and 10% of the administered radioactivity, respectively. 

Hydrogen sulfide is excreted primarily as sulfate (free sulfate or thiosulfate) in the urine. It is also excreted unchanged in exhaled air and in feces and flatus. 

Organic Lead. Urinary lead levels were elevated for 4 days in a man accidentally exposed to an unknown quantity of tetramethyl lead (Gething 1975). Exhalation of the tetraalkyl lead compounds following inhalation exposure is a major route of elimination in humans. At 48 hours postexposure, 40% and 20% of the initially inhaled tetramethyl and tetraethyl lead doses, respectively, were exhaled with low urinary excretion (Heard et al. 1979). 

Cystic fibrosis is the most common lethal autosomal-recessive disease, in which oxidative stress takes place at the airway surface [274]. This disease is characterized by chronic infection and inflammation. Enhanced free radical formation in cystic fibrosis has been shown as early as 1989 [275] and was confirmed in many following studies (see references in Ref. [274]). Contemporary studies also confirm the importance of oxidative stress in the development of cystic fibrosis. Ciabattoni et al. [276] demonstrated the enhanced in vivo lipid peroxidation and platelet activation in this disease. These authors found that urinary excretion of the products of nonenzymatic lipid peroxidation PGF2 and TXB2 was significantly higher in cystic fibrotic patients than in control subjects. It is of importance that vitamin E supplementation resulted in the reduction of the levels of these products of peroxidation. Exhaled ethane, a noninvasive marker of oxidative stress, has also been shown to increase in cystic fibrosis patients [277]. 

The primary metabolites of hexachloroethane are eventually oxidized to form trichloroethanol and trichloroacetic acid. These ultimate metabolites are excreted along with unchanged hexachloroethane, tetrachloroethene, and pentachloroethane. A small amount of the absorbed hexachloroethane is oxidized completely to carbon dioxide. Hexachloroethane and its metabolites are removed from the body in exhaled... 

Based on the amount of label found in rabbit urine and exhaled air, 19-29% of a 500 mg/kg dose was absorbed (Jondorf et al. 1957). Since some hexachloroethane would be excreted in bile and found in fecal matter, the actual amount absorbed was larger than 30%, perhaps 40-50%. 

Orally ingested hexachloroethane is exhaled and excreted in mine and fecal matter. The portion of the hexachloroethane found in fecal matter is the result of excretion in bile. The results of studies that measured the amount of residual hexachloroethane in excreta can be misleading, since much of the absorbed hexachloroethane is metabolized to other compounds. Measurement of 14C label after exposure to labeled compound presents a more complete picture of ultimate hexachloroethane fate and excretion than measurement of hexachloroethane. 

Absorption, Distribution, Metabolism, and Excretion. There are no mechanistic or quantitative studies of hexachloroethane absorption from the lungs or across the gastrointestinal tract or skin. However, absorption does occur following oral exposure based on the appearances of hexachloroethane and its metabolites in blood, urine, and exhaled air (Fowler 1969b Gorzinski et al. 1985 Jondorf et al. 1957 Mitoma... 

Metabolism in the rat is qualitatively similar to that in humans. Four male and four female Wistar rats were exposed individually to 14C-labeled HFC134a at 10,000 ppm for 1 h (Ellis et al. 1993). Atmospheres were monitored with a gas chromatograph. After exposure, urine and feces were collected at 6 h intervals up to 24 h and every 24 h for up to 5 d thereafter. Approximately 1% of the inhaled dose was recovered in urine, feces, and expired air of that 1%, approximately two-thirds was exhaled within 1 h postexposure as unchanged HFC-134a. Exhaled C02 was the primary metabolite and accounted for approximately 0.22% and 0.27% of the inhaled dose in males and females, respectively. Excretion in the urine and feces occurred within 24 h and accounted for 0.09% and 0.04% of the inhaled dose, respectively. The only metabolite identified in urine was trifluoroacetic acid. At sacrifice, 5 d postexposure, radioactivity was uniformly distributed among tissues and accounted for 0.14-0.15% of the inhaled dose. The average total metabolized dose in male and female rats was 0.37% of the inhaled dose. 

A small part of divalent mercury is reduced to mercury vapour. This reduction probably accounts for the ability of certain commonly occurring microorganisms to volatilize mercury for biological media [59]. Loss of volatile radioactive mercury was observed in rats injected with salts of divalent mercury labelled with the 203Hg isotope [60]. Part of the volatile mercury was exhaled via the lungs, the remainder by way of the skin and fur. The volatile loss accounted for up to 20% of the total rate of excretion of mercury from the animals. 

Approximately 10-20% of -hexane absorbed by inhalation is excreted unchanged in exhaled air the remainder is metabolized. Metabolism takes place via mixed-function oxidase reactions in the liver. In a study in which metabolites were measured in workers exposed to 77-hexane (Perbellini et al. 1981), mean concentrations of 77-hexane metabolites in urine were 2,5-hexanedione, 5.4 mg/L 2,5-dimethylfuran,... 

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