Lung Overload, Dosimetry of Lung Fibrosis and Their Implications to the Respiratory Dust Standard

Long-term inhalation of high concentrations of various insoluble dusts has resulted in a spectrum of pulmonary changes in rats, collectively attributed to lung overload. Depending on the experimental conditions, the pulmonary alterations range in severity from moderate and persistent inflammation to fibrosis and lung tumours. We focused on lung fibrosis, and developed a dosimetric approach which correlates the retained dose of dust in the lungs, per gram of lung tissue, to the induction of pulmonary fibrosis. In studies with test toner, the attainment of a normalized pulmonary dose of 300–600 mg · day g⁻¹ was a reliable predictor of pulmonary fibrosis, when diagnosed using Masson trichrome staining. When applied to a different toner, it correctly predicted fibrosis above a normalized dose of 600 mg·day g⁻¹. It was equally successful upon application to a chronic inhalation study examining carbon black, diesel engine exhaust and titanium dioxide in Wistar rats. Validation of this relationship may provide a quantitative index for use in the identification of 〈innocuous' respirable dusts as well as enable the determination of a toxicologically based permissible human exposure limit for such materials. Calculations of lung burdens and threshold doses of innocuous respirable dusts in humans strongly suggest that the adequacy of the current occupational, respirable PNOC (Particles Not Otherwise Classified) limit of 5 mg m⁻³ be re-examined, with a view to lowering it.