Inhalation tolerance study for p-aramid respirable fiber-shaped particulates (RFP) in rats

This study was designed to assess the lung clearance function in rats after subchronic exposure to p-aramid respirable fiber-shaped particulates (RFP) . Male Wistar rats were exposed 6 hrs/day, 5 days/week for 3 months to 50, 200, and 800 RFP/ml measured by scanning electron microscopy (SEM). Recover y effects were followed up through 9 months postexposure. The retention of RFP (length > 5 mu m) was about 25 x 10(6) RFPs per lung in the low dose gr oup after 3 months of exposure. The corresponding values in the medium and high dose groups amounted to overproportionally higher values of 122 x 10(6 ) and 576 x 10(6) RFPs per lung, respectively. A decrease in the length of the retained RFPs over the 9-month recovery period was observed, indicating a breakage of long fibrils. Alveolar clearance half-times measured by gamm a tracers indicated a dust overloading of lungs for the high dose group at 0 and 3 months postexposure. Bronchoalveolar lavage parameters revealed tha t p-aramid RFPs induced pronounced inflammatory effects in the high and med ium dose groups. Histopathologically, slight fibrotic and hyperplastic lesi ons were observed in the medium and high dose groups directly after the end of exposure. The findings at the 3-month postexposure interval resulted in a reduction of inflammatory changes in the medium and high dose groups com pared to the sacrifices upon cessation of exposure. No histopathologic effe cts were detected in the low dose group. In the high dose group the maximum functionally tolerated dose was exceeded. The No Observed Adverse Effect L evel (NOAEL) of RFP was 50 RFP/ml as measured by SEM.