Effects of nonfibrous particles on ceramic fiber (RCF1) toxicity in rats.

In previous investigations a reference test sample of prepared ceramic fibers called RCF1 induced lung tumors in a 2-yr inhalation study in rats. It was hypothesized that nonfibrous particles in RCF1 may have played a significant role. The objective of the present study was to compare lung retention and biological effects of another sample of ceramic fibers, called RCF1a, to the original RCF1. The main difference between these 2 samples was the content of nonfibrous particles: 25% of the mass of RCF1 versus 2% for RCF1a. These nonfibrous particles were chemically identical to the fibers. Female Wistar rats were exposed 6 h/day, 5 days/wk for 3 wk to either RCF1a or RCF1 fiber aerosol at a concentration of about 125 fibers (>20 microm long)/ml. Because of differences in the nonfibrous particle contents, the average gravimetric aerosol concentration differed between the two samples (RCF1, 51.2 mg/m(3); RCF1a, 25.8 mg/m(3)). The posttreatment observation period was 12 mo. Biological effects measured include the clearance function of alveolar macrophages (clearance of fibers and tracer particles), and inflammation and its persistence during the recovery period. Alveolar clearance of tracer particles ((46)Sc(2)O(3)) was barely retarded after RCF1a exposure (80 days clearance half-time compared to 60 days in controls). After RCF1 exposure, however, a severe retardation of clearance was observed (1200 vs. 66 days). In both groups, differential cell counts on pulmonary lavage showed a significant increase of polymorphonuclear leukocytes (PMNs) (about 15%) and lymphocytes 3 days after the end of exposure. The PMN influx persisted longer after exposure to RCF1 than RCF1a. The conclusion of the study is that the particle fraction of RCF1 significantly enhanced any adverse effects. This clearly demonstrates the importance of the physical characteristics of the test material for the degree of toxic effects to be expected. The presence of nonfibrous particulates can enhance the effects on the lung of a mixture of fibrous and nonfibrous particulates following exposure.