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. 1995 May;52(5):344–352. doi: 10.1136/oem.52.5.344

Physiologically based pharmacokinetic model for acetone.

S Kumagai 1, I Matsunaga 1
PMCID: PMC1128228  PMID: 7795758

Abstract

OBJECTIVE--This study aimed to develop a physiologically based pharmacokinetic model for acetone and to predict the kinetic behaviour of acetone in the human body with that model. METHODS--The model consists of eight tissue groups in which acetone can be distributed: the mucous layer of the inhaled air tract, the mucous layer of the exhaled air tract, a compartment for gas exchange (alveolus of the lung), a group of blood vessel rich tissues including the brain and heart, a group of tissues including muscles and skin that have low perfusion rates, a group of fatty tissues, an organ for metabolism (liver), and a compartment for urinary excretion (kidney). A mucous layer in the model is only the outermost layer of the mucus lining the wall of the air tract during inhalation and exhalation. To check the relevance of the model, the simulated results were compared with the experimental data. Next, simulation was conducted by changing the volume of the mucous layer and the respiratory rate to clarify the effect of these variables. Finally, simulation of an occupational situation was performed. RESULTS--With an appropriate value for the volume of mucous layer, the simulated acetone concentrations in arterial blood, end exhaled air, urine, and fatty tissue were found to agree well with the experimental data. The volume of mucous layer and rate of respiration were critical for the appropriate simulation. The simulated occupational situation fitted the observed regression line in field studies quite well. The simulation also enabled predictions to be made about the characteristic kinetics for water soluble solvents. CONCLUSION--The model is useful for understanding and explaining the kinetics of acetone.

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Selected References

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  1. Adolph E. F. Quantitative Relations in the Physiological Constitutions of Mammals. Science. 1949 Jun 10;109(2841):579–585. doi: 10.1126/science.109.2841.579. [DOI] [PubMed] [Google Scholar]
  2. Droz P. O., Guillemin M. P. Human styrene exposure. V. Development of a model for biological monitoring. Int Arch Occup Environ Health. 1983;53(1):19–36. doi: 10.1007/BF00406174. [DOI] [PubMed] [Google Scholar]
  3. Fernández J. G., Droz P. O., Humbert B. E., Caperos J. R. Trichloroethylene exposure. Simulation of uptake, excretion, and metabolism using a mathematical model. Br J Ind Med. 1977 Feb;34(1):43–55. doi: 10.1136/oem.34.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fiserova-Bergerova V., Diaz M. L. Determination and prediction of tissue-gas partition coefficients. Int Arch Occup Environ Health. 1986;58(1):75–87. doi: 10.1007/BF00378543. [DOI] [PubMed] [Google Scholar]
  5. Fiserova-Bergerova V., Vlach J., Singhal K. Simulation and prediciton of uptake, distribution, and exhalation of organic solvents. Br J Ind Med. 1974 Jan;31(1):45–52. doi: 10.1136/oem.31.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fujino A., Satoh T., Takebayashi T., Nakashima H., Sakurai H., Higashi T., Matumura H., Minaguchi H., Kawai T. Biological monitoring of workers exposed to acetone in acetate fibre plants. Br J Ind Med. 1992 Sep;49(9):654–657. doi: 10.1136/oem.49.9.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hallier E., Filser J. G., Bolt H. M. Inhalation pharmacokinetics based on gas uptake studies. II. Pharmacokinetics of acetone in rats. Arch Toxicol. 1981 Jul;47(4):293–304. doi: 10.1007/BF00332395. [DOI] [PubMed] [Google Scholar]
  8. Hartley L. H., Grimby G., Kilbom A., Nilsson N. J., Astrand I., Bjure J., Ekblom B., Saltin B. Physical training in sedentary middle-aged and older men. 3. Cardiac output and gas exchange asubmaximal and maximal exercise. Scand J Clin Lab Invest. 1969 Dec;24(4):335–344. doi: 10.3109/00365516909080170. [DOI] [PubMed] [Google Scholar]
  9. Johanson G. Modelling of respiratory exchange of polar solvents. Ann Occup Hyg. 1991 Jun;35(3):323–339. doi: 10.1093/annhyg/35.3.323. [DOI] [PubMed] [Google Scholar]
  10. Johanson G. Physiologically based pharmacokinetic modeling of inhaled 2-butoxyethanol in man. Toxicol Lett. 1986 Nov;34(1):23–31. doi: 10.1016/0378-4274(86)90141-4. [DOI] [PubMed] [Google Scholar]
  11. Koizumi A. Potential of physiologically based pharmacokinetics to amalgamate kinetic data of trichloroethylene and tetrachloroethylene obtained in rats and man. Br J Ind Med. 1989 Apr;46(4):239–249. doi: 10.1136/oem.46.4.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kumagai S., Matsunaga I. Effect of variation of exposure to airborne chlorobenzene on internal exposure and concentrations of urinary metabolite. Occup Environ Med. 1995 Jan;52(1):65–70. doi: 10.1136/oem.52.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mizunuma K., Yasugi T., Kawai T., Horiguchi S., Ikeda M. Exposure-excretion relationship of styrene and acetone in factory workers: a comparison of a lipophilic solvent and a hydrophilic solvent. Arch Environ Contam Toxicol. 1993 Jul;25(1):129–133. doi: 10.1007/BF00230723. [DOI] [PubMed] [Google Scholar]
  14. Morris J. B., Cavanagh D. G. Deposition of ethanol and acetone vapors in the upper respiratory tract of the rat. Fundam Appl Toxicol. 1986 Jan;6(1):78–88. doi: 10.1016/0272-0590(86)90266-6. [DOI] [PubMed] [Google Scholar]
  15. Morris J. B., Cavanagh D. G. Metabolism and deposition of propanol and acetone vapors in the upper respiratory tract of the hamster. Fundam Appl Toxicol. 1987 Jul;9(1):34–40. doi: 10.1016/0272-0590(87)90151-5. [DOI] [PubMed] [Google Scholar]
  16. Morris J. B., Hassett D. N., Blanchard K. T. A physiologically based pharmacokinetic model for nasal uptake and metabolism of nonreactive vapors. Toxicol Appl Pharmacol. 1993 Nov;123(1):120–129. doi: 10.1006/taap.1993.1228. [DOI] [PubMed] [Google Scholar]
  17. PRICE T. D., RITTENBERG D. The metabolism of acetone. I. Gross aspects of catabolism and excretion. J Biol Chem. 1950 Jul;185(1):449–459. [PubMed] [Google Scholar]
  18. Perbellini L., Mozzo P., Olivato D., Brugnone F. "Dynamic" biological exposure indexes for n-hexane and 2,5-hexanedione, suggested by a physiologically based pharmacokinetic model. Am Ind Hyg Assoc J. 1990 Jul;51(7):356–362. doi: 10.1080/15298669091369781. [DOI] [PubMed] [Google Scholar]
  19. Ramsey J. C., Andersen M. E. A physiologically based description of the inhalation pharmacokinetics of styrene in rats and humans. Toxicol Appl Pharmacol. 1984 Mar 30;73(1):159–175. doi: 10.1016/0041-008x(84)90064-4. [DOI] [PubMed] [Google Scholar]
  20. Sato A., Endoh K., Kaneko T. [Individual differences in the kinetic behavior of trichloroethylene. A simulation study using a physiological pharmacokinetic model]. Sangyo Igaku. 1989 Sep;31(5):348–354. doi: 10.1539/joh1959.31.348. [DOI] [PubMed] [Google Scholar]
  21. Stahl W. R. Scaling of respiratory variables in mammals. J Appl Physiol. 1967 Mar;22(3):453–460. doi: 10.1152/jappl.1967.22.3.453. [DOI] [PubMed] [Google Scholar]
  22. Wigaeus E., Holm S., Astrand I. Exposure to acetone. Uptake and elimination in man. Scand J Work Environ Health. 1981 Jun;7(2):84–94. doi: 10.5271/sjweh.2561. [DOI] [PubMed] [Google Scholar]
  23. Wigaeus E., Löf A., Nordqvist M. B. Uptake, distribution, metabolism, and elimination of styrene in man. A comparison between single exposure and co-exposure with acetone. Br J Ind Med. 1984 Nov;41(4):539–546. doi: 10.1136/oem.41.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]

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