Establishment of a Bioassay System for Detection of Lung Toxicity Due to Fine Particle Instillation: Sequential Histopathological Changes with Acute and Subacute Lung Damage Due to Intratracheal Instillation of Quartz in F344 Male Rats

In order to establish an appropriate bioassay for detection of lung damage after fine particle inhalation, sequential histopathological changes were here examined after intratracheal instillation of quartz (DQ-12, 4 mg/rat), as a typical lung toxic agent, in F344 male rats. A total of 50, 10-week-old animals, were separated into two groups. Twenty five were exposed to the material suspended in saline (0.2 ml) using a specially designed aerolizer and subgroups were sacrificed 1, 3, 7, 14, and 28 days thereafter. The remaining 25 rats were exposed by intratracheal instillation to saline (0.2 ml) as a control group and were sacrificed on the same days. Both groups received intraperitoneal injections of BrdU before sacrifice, and both groups underwent assessment of lung histopathology with immunohistochemical demonstrations of BrdU, iNOS and MMP-3 as end-point markers. The results suggest that Days 1 and 28 after intratracheal instillation of test fine particles are the most appropriate for detection of acute and subacute inflammatory changes, respectively. Furthermore, BrdU on Day 1 and iNOS on Day 28 proved to be suitable end-point markers for this purpose. Although instillation and inhalation models are different, the present instillation model can be used for detection of acute or subacute lung toxicity due to inhaled fine particles.