Induction of Inflammation and Fibrosis after Exposure to Insoluble and Isometric Particles

Abstract

Several published reports show that long-term inhalation of large quantities of non-fibrous, innocuous particles such as TiO₂, carbon black, petroleum coke, toner, and other polymeric materials can result in a spectrum of pulmonary changes. Exposure of F344 rats to 0, 1, 4 or 16 mg/m³ of test toner for 6 hours/day, 5 days/week resulted in inflammatory changes determined by broncho-alveolar lavage at the two highest exposure levels after 15 months. Minimal to mild pulmonary fibrosis was detected in 22% of the group at 4 mg/m³, while mild to moderate fibrosis was observed in 92% of the high exposure group at the termination of the study (25.5 months). In another experiment, F344 rats were exposed to the same test toner at 40 mg/m³ for 3-months and observed for 15-months post-exposure. The inflammatory changes, detected after exposure, persisted during the entire period of observation. In both of these experiments, the observed effects were interpreted in terms of “lung overloading”. The presence of large quantities of insoluble, non-fibrous particles, generally considered to be innocuous, leads to an inflammatory response in the lungs. Depending on the duration and magnitude of the insult, the long-term presence of the foreign material in the lungs can lead to histopathological changes which included lipoproteinosis, fibrosis, and in some cases neoplasia.