RETENTION - CLEARANCE Yves Alarie, Ph.D University of Pittsburgh,USA Professor Emeritus University of Pittsburgh,USA

A. MODEL A model proposed by the Task Group on Lung Dynamics is used. This model is shown in Figure 18 and includes the following items previously presented.

a) Mass concentration in the air. b) Particle size to determine percentage deposition in each portion of the respiratory tract. c) Class of particles in terms of clearance time.

B. INPUTS FOR THE MODEL These are given in Table 10 and include the following: D1: Total dust concentration in inhaled air (mg/m3) D2: Total dust concentration in exhaled air (mg/m3) D3: Total dust deposited in N-P compartment (mg) D4: Total dust deposited in T-B compartment (mg) D5: Total dust deposited in P compartment (mg)

C. OUTPUTSFOR THE MODEL: CLEARANCE,HALF-LIVES,PATHWAYS AND MECHANISMS These are given in Table 10 in an attempt to summarize all of these items. First, look at Figure 18, for each letter on this Figure there is an explanation for it in Table 10. Don’t believe the numbers in Table 10. Use them for relative comparisons rather than absolute numbers.

F. IMPLICATION OF THE MODEL With availability of computers it is now easier to predict aerosol accumulation and clearance in the respiratory tract (17,18). An example: 17. Snipes, M. B. Long-term retention and clearance of particles by mammalian species. CRC Crit. Rev. Toxicol. 20, 175-211, 1989. 18. Oberdorster, G. Deposition and retention modeling of inhaled cadmium in rat and human lung: An example for extrapolation of effects and risk estimation. In: Extrapolation of dosimetric relationships for inhaled particles and gases. Academic Press, NY, pp. 345-370, 1989.

Click for larger picture Also, while clearance is obviously slow for insoluble particles, at one point an equilibrium will exist. For example, coal miners will have about 5 to 15 mg of coal dust/g of lung despite chronic exposure. Note: Despite the availability of computer models, clearance of insoluble particles in chronic exposures can be dependent upon exposure concentration, particularly at high concentrations. See Morrow, P. E., Haseman, J. K., Hobbs, C. H., Driscoll, K. E., Vu, V. and Oberdorster, G. The maximum tolerated dose for inhalation bioassays: toxicity vs. overload. Fund. Appl. Toxicol. 29, 155-167, 1996.