POCK model simulations of pulmonary quartz dust retention data in extended inhalation exposures of rats.
In recent years, a physiology-oriented multicompartmental kinetics (POCK) model was developed to simulate pulmonary retention data of biopersistent, noncytotoxic aerosols in long-term inhalation exposures of rats. Experimental data were successfully simulated for submicrometer-sized aerosols like carbon black, diesel soot, and titanium dioxide and for a micrometer-sized xerographic toner aerosol (Stöber et al., 1994, 1995). This article describes for various rat strains successful POCK model simulations of experimental pulmonary retention data of micrometer-sized aerosols of biopersistent cytotoxic SiO2 modifications like quartz and quartzite. In the past, the POCK model was not applied to cytotoxic aerosols and dusts. Cytotoxicity was considered incompatible with the model assumption of a constant macrophage lifetime independent of the macrophage aerosol load. The few relevant experimental retention studies with biopersistent silica found in the open literature showed particulate lung burdens up to some 15 mg per rat lung. Apparently, at these loads, pulmonary burdens could be simulated because the fraction of alveolar macrophages killed by the cytotoxic particles was possibly still small compared to the total number of viable macrophages. Of necessity, however, the classical alveolar clearance in these studies was exclusively performed by alveolar macrophages that were burdened with cytotoxic particles, and the cells appeared to suffer from a substantial initial decrease of their inherent mobility. Thus a sizeable reduction of the alveolar clearance rate coefficient in comparison to nontoxic aerosol was found. The results for the model parameters of several different exposure studies are shown and interpreted in comparison to nontoxic titanium dioxide retention parameters.
Stöber
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Chemical Institute of Technology, PO Box 12137, Research Triangle Park, NC 27709, USA. stoeber@ciit.org.
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001822:Body Burden; D003198:Computer Simulation; D004391:Dust / Q000009:adverse effects*; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008962:Models, Theoretical; D011009:Pneumoconiosis / Q000209:etiology / Q000378:metabolism*; D011791:Quartz / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D014025:Titanium / Q000008:administration & dosage / Q000493:pharmacokinetics
D000336:Aerosols; D004391:Dust; D011791:Quartz; C009495:titanium dioxide; D014025:Titanium