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

Citation
B. Bellmann et al., Effects of nonfibrous particles on ceramic fiber (RCF1) toxicity in rats, INHAL TOXIC, 13(10), 2001, pp. 877-901
Citations number
37
Categorie Soggetti
Pharmacology & Toxicology
Journal title
INHALATION TOXICOLOGY
ISSN journal
08958378 → ACNP
Volume
13
Issue
10
Year of publication
2001
Pages
877 - 901
Database
ISI
SICI code
0895-8378(200110)13:10<877:EONPOC>2.0.ZU;2-7
Abstract
In previous investigations a reference test sample of prepared ceramic fibe rs called RCF1 induced lung tumors in a 2-yr inhalation study in rats. It w as hypothesized that nonfibrous particles in RCF1 may have played a signifi cant 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 c ontent of nonfibrous particles: 25% of the mass of RCF1 versus 2% for RCF1a . These nonfibrous particles were chemically identical to the fibers. Femal e Wistar rats were exposed 6 h/day, 5 days/wk for 3 wk to either RCF1a or R CF1 fiber aerosol at a concentration of about 125 fibers ( >20 mum long)/ml . Because of differences in the nonfibrous particle contents, the average g ravimetric 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 alveol ar macrophages (clearance of fibers and tracer particles), and inflammation and its persistence during the recovery period. Alveolar clearance of trac er particles (Sc-46(2) O-3) was barely retarded after RCF1a exposure (80 da ys clearance halftime 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 si gnificant increase of polymorphonuclear leukocytes (PMNs) (about 15%) and l ymphocytes 3 days after the end of exposure. The PMN influx persisted longe r after exposure to RCF1 than RCF1a. The conclusion of the study is that th e particle fraction of RCF1 significantly enhanced any adverse effects. Thi s clearly demonstrates the importance of the physical characteristics of th e test material for the degree of toxic effects to be expected. The presenc e of nonfibrous particulates can enhance the effects on the lung of a mixtu re of fibrous and nonfibrous particulates following exposure.