USE OF SHORT-TERM ASSAYS TO EVALUATE THE POTENTIAL TOXICITY OF TWO NEW BIOSOLUBLE GLASSWOOL FIBERS

Abstract

Two new glasswools were developed for optimal biosolubility in the lung: JM 902, for insulation and filtration; and JM 901F, for standard thermal and acoustical insulation. Both were tested for lung biopersistence and their potential to induce persistent pulmonary inflammation in rats. Their dissolution rate constants (k dis) were estimated in vitro. Results for 902 were: in vitro k dis (pH 7.4) = 150 ng/cm 2 /h; after 5 days of fiber inhalation (IH), lung clearance of fibers > 20 µm length (F > 20 µm) indicated a weighted half-time (WT 1/2) of 6.8 days and 90% clearance time (T90) of 33 days; following intratracheal instillation (IT), lung clearance half-time (T 1/2) for F > 5 µm was 20 days. Results for 901F were: k dis (pH 7.4) = 500-560; after 5 days of fiber inhalation exposure, WT 1/2 (F > 20 µm) = 8.1 days and T90 = 38 days. After 5 days of fiber inhalation, both fibers induced initial pulmonary inflammation followed by return to normal within 3 wk postexposure. Lung clearance half-times for 902 and 901F passed the European Union (EU) criteria for noncarcinogenic fibers (IH WT 1/2 F > 20 µm was < 10 days); 902 passed the noncarcinogenic criterion of the German government (IT T 1/2 F > 5 µm was < 45 days). Thus, carcinogenicity labeling is not required for either fiber in the EU. Short-term test results for 902 and 901F were similar to results for synthetic vitreous fibers (SVFs) that were innocuous in rodent chronic inhalation studies, but short-term test results for 902 and 901F differed sharply from results for other SVFs that were pathogenic in chronic studies. Thus, these short-term tests indicate that 902 and 901F are biosoluble fibers and would be nonpathogenic in the rat exposed by inhalation.