Ann. occup Hyg., Vol 35, No. 3, pp. 323-339, 1991 Printed in Great Britain. 0003-4878/91 S3 00+000 Pergamon Press pic © 1991 British Occupational Hyjreoe Society. \ MODELLING OF RESPIRATORY EXCHANGE OF POLAR SOLVENTS^ GUNNAR JOHANSON National Institute of Oecupatlonal Health, S-171 84 Sekia, Sweden; and Department of Occupational Medicine, University Hospital, S-751 85 Uppsala, Sweden (Received 30 August 1990 and in final form 18 September 1990) Abstract—Physiologically based pharmacokinetic (pbpk) models are frequently used to describe the kinetics of inhaled gases and vapours. In these models the conducting airways of the respiratory tract are generally assumed to act as inert tubes. The function of the inert tubes is merely to conduct the vapour to the alveolar regions where the actual exchange between ambient air and body takes place. Such an 'inert tube' model may be adequate to describe the inhalation and exhalation kinetics of inert vapours, for example non-polar solvents which have a low water solubility. Experimental data suggest, however, that the 'inert tube' model may be erroneous for polar solvents which have a high water solubility. To explore this possibility further a tentative pbpk model was developed. Model structure and parameters were obtained from the literature on lung anatomy and physiology and by visual fitting to experimental acetone, carbon dioxide, diethyl ether and ethanol data. The model was written and solved by spreadsheet programming on a personal computer. Simulations were carried out to illustrate the difference between end-exhaled and alveolar air and how water solubility and workload influence the uptake and excretion kinetics of polar solvents. It is concluded that the model is valuable for predicting the lung kinetics of polar vapours under various circumstances. It may therefore be useful in the development of biological monitoring methods based on breath sampling and help us to understand and to explain experimental data. NOMENCLATURE pbpk Symbols C D F L M P Q T V Subscripts alv / b/a c^ end I in out P pulm sys w/a physiologically based phan concentration diffusion constant transfer or clearance term partition coefficient length (of tube) molecular weight pressure or partial pressure flow absolute temperature volume alveolar air blood/air central compartment end-exhaled air index of region air entering tube air leaving tube peripheral compartment pulmonary air systemic circulation water/air • Pape r based on a presentation made at the International Workshop on Pharmacokinetic Modelling in Occupational Health, Leysin, Switzerland, in March 1990. 323