Updating the icrp human respiratory tract model

Briefly, the model structure (illustrated in ) or particle translocation to the interstitial region (rate: KI); and the very slow (irreversible) translocation of interstitialized material in the hilar (lung-associated) lymph nodes (rate: KLN) The original parameter estimation for this model was performed using a systematic grid search within biologically plausible ranges of KT, KI, and KLN (identified from human and animal studies in the literature; Table 4 of Kuempel et al., 2001a).In addition, a fixed value of the average alveolar deposition fraction (ICRP, 1994) was estimated on the reported airborne coal mine particle size data (Jones et al., 1988a; Burkhart et al., 1987).The model structure consists of deposition of inhaled particles in the pulmonary (alveolar) region, clearance from the alveolar region to the tracheo-bronchial region or translocation to the lung interstitium, and irreversible sequestration of interstitialized material.Each of these processes was described as first order.Lung dust burden was measured for 141 of these coal miners, who were autopsied between 19.Of the 141 miners, 128 miners had the minimal information specified in the original model parameter calibration, which included (in addition to the lung dust burden), the duration of employment in mining, the mining job history (to assign job-specific exposure concentration), and the dates and/or ages at retirement and death (to compute the post-exposure duration) (Kuempel et al., 2001a).

Previous analyses also showed that the process of dose-dependent overloading of lung clearance as observed in rats did not adequately fit the coal miner data (Kuempel, 2000; Kuempel et al., 2001a; Tran and Buchanan, 2000).

The US data are from a study by the late Werner Laqueur, M.

D., who systematically collected approximately 600 cases from consecutive autopsies at Beckley Appalachian Regional Hospital in West Virginia.

For the current analysis, Bayesian population analysis using Markov chain Monte Carlo (MCMC) simulation is considered an appropriate method for calibrating this particle clearance and retention model.

This approach permits parameters to be simultaneously calibrated for multiple data sets using uninformative prior parameter distributions that minimize bias (Bernillon and Bois, 2000; Lunn et al., 2009; Jonsson and Johanson, 2003; Hack, 2006; Hack et al., 2006).

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A biomathematical model was previously developed to describe the long-term clearance and retention of particles in the lungs of coal miners.

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