Uptake of 10 polar organic solvents during short-term respiration

Abstract

Respiratory uptake was investigated for 10 polar organic solvents with high blood/air partition coefficients (lambda(blood/air)): ethyl acetate (lambda(blood/air), 77), methyl iso-butyl ketone (90), methyl acetate (90), methyl propyl ketone (150), acetone (245), iso-pentyl alcohol (381), iso-propyl alcohol (848), methyl alcohol (2590), ethylene glycol monobutyl ether (EGBE, 7970), and propylene glycol monomethyl ether (PGME, 12380). Test-air concentrations (Cinh) were 25 to 200 ppm. Four healthy male volunteers inhaled the test air for 10 min at rest and then room air for 5 min. The percentage of solvent in the end-exhaled air and in the mixed-exhaled air increased after the start of the test-air respiration, and reached a quasi-steady-state level within a few min. The speeds of these increases at the start of the test-air respiration became lower as lambda(blood/air) increased. The mean uptakes (U) for the last five min of the test air respiration were 67.3, 52.9, 60.4, 53.0, 52.6, 63.0, 60.3, 60.8, 79.7, and 81.3%, respectively, for ethyl acetate, methyl iso-butyl ketone, methyl acetate, methyl propyl ketone, acetone, iso-pentyl alcohol, iso-propyl alcohol, methyl alcohol, EGBE and PGME. Thus, U values of the alcohols were higher than those of the ketones and lower than the glycol ethers. The overall view, except for esters, showed that U increased with lambda(water/air) increases. This tendency can be explained by a hypothesis that solvent absorbed in the mucus layer of the respiratory tract is removed by the bronchial blood circulation. U values of ethyl acetate and methyl acetate were higher than those of methyl iso-butyl ketone and methyl propyl ketone, though the lambda(blood/air) values of these esters were nearly equal to those of the ketones. For the respiration of the esters, their metabolites, ethyl alcohol and methyl alcohol, were detected in the exhaled air. The exhalation percentage of the metabolites increased after the start of test-air respiration and reached a quasi-steady-state level of 2 and 3%, respectively, by the 5th min. These data suggest that removal of the solvent via metabolism in the wall tissue of the respiratory tract plays an important role for the esters.

A Lung Model Describing Uptake of Organic Solvents and Roles of Mucosal Blood Flow and Metabolism in the Bronchioles

“…In our previous study (Kumagai et al, 1999), solvent concentrations in the end-exhaled air (C end ) and in the mixed exhaled air (C mix ) were determined during 10-min exposure of 7 polar organic solvents, methyl iso-butyl ketone, methyl propyl ketone, acetone, iso-propyl alcohol, methyl alcohol, ethylene glycol monobutyl ether, and propylene glycol monomethyl ether (Table 2), where C end is an instantaneous solvent concentration in exhaled air at the end of exhalation, and C mix is a mean solvent concentration in air exhaled during the whole exhalation. In our experiment (Kumagai et al, 1999), the solvent concentration in exhaled air was measured by continuously introducing a part of exhaled air to a flame ionization detector and C end was determined to be the solvent concentration at the end of exhalation. Also, exhaled air was collected in a Tedlar bag during the whole exhalation and C mix was determined by a gas chromatograph.…”

“…E end for CL Body = 0 was predicted to be higher by 0.05-0.17 than E end for CL Body = ¥ when l B < 10, but these values were close to each other when l B > 50. Figure 2 also shows the observed values of E end in studies by Kumagai et al (1999), Jones et al (1990), Astrand et al (1973Astrand et al ( , 1974Astrand et al ( , 1975Astrand et al ( , 1976Astrand et al ( , 1978, Fernandez et al (1976), Carlsson (1982), Dossing et al (1984), Pezzagno et al (1985), and Wigaeus et al (1981), selected according to the criteria given earlier. These values agree well with the model prediction, though the 3 values deviated by more than 0.05.…”

“…These values agree well with the model prediction, though the 3 values deviated by more than 0.05. (Astrand et al, 1975) (9.7;Sato & Nakajima, 1979b), tetrachloroethylene (Fernandez et al, 1976) (13;Sato & Nakajima, 1979b), toluene (Carlsson, 1982;Dossing et al, 1984) (16;Sato & Nakajima, 1979a), xylene (Astrand et al, 1978) (26;Sato & Nakajima, 1979a), styrene (Pezzagno et al, 1985;Astrand et al, 1974) (52;Sato & Nakajima, 1979a), methyl iso-butyl ketone (Kumagai et al, 1999) (90;Sato & Nakajima, 1979a), methyl propyl ketone (Kumagai et al, 1999) (150;Sato & Nakajima, 1979a), acetone (Kumagai et al, 1999;Wigaeus et al, 1981) (245;Sato & Nakajima, 1979a), butanol (Astrand et al, 1976) (677;Kaneko et al, 1994), iso-propyl alcohol (Kumagai et al, 1999) (848;Kaneko et al, 1994), methanol (Kumagai et al, 1999(Kumagai et al, ) (2590Kaneko et al, 1994), ethylene glycol monobutyl ether (Kumagai et al, 1999) (7970;Johanson & Dynesius, 1988), propylene glycol monomethyl ether (Kumagai et al, 1999) (12,400;Johanson & Dynesius, 1988 (Monster, 1979;Pezzagno et al, 1988), trichloroethylene (Monster, 1979) (9.5; Sato & Nakajima, 1979b), tetrachloroethylene (Monster, 1979;Pezzagno et al, 1988), toluene (Pezzagno et al, 1988), xylene (Pezzagno et al, 1988), styrene …”

“…Solvent molecules that diffuse into the mucosal tissue are removed by the metabolism for some solvents (e.g., esters) (Kumagai et al, 1999). In the MBM model, the two behaviors of diffusion and removal are also described as removal by a hypothetical metabolism in the mucus layer.…”

Final Report on the Safety Assessment of Methoxyisopropanol and Methoxyisopropyl Acetate as Used in Cosmetics

“…Methoxyisopropanol was rapidly excreted in the urine with a half-life of less than 2.6 h. Metabolites of Methoxyisopropanol in the urine were not measured. Kumagai et al (1999) exposed four healthy male volunteers to 25, 50, and 100 ppm Methoxyisopropanol for 10 min and determined the uptake of the Methoxyisopropanol by the lungs. The mean uptake of Methoxyisopropanol in the last 5 min of exposure was 81.3%.…”