Subchronic inhalation study of stone wool fibres in rats.
Pathology results after subchronic inhalation in rats of three separate fibres representing the new biosoluble high-aluminium low-silica HT type stone wool are given, and the results were compared with the results from a similar study done with the traditional stone wool MMVF21. Male Wistar rats were exposed at one exposure level by nose-only inhalation to well-characterized fibre test atmospheres. The fibres had been size selected to be largely rat respirable. The target dose was an exposure to 150 long fibres/ml (length>20 microm) in each group, and this dose was achieved for all the fibres. The negative control groups were exposed to filtered air. The exposure duration was 6 h/day, 5 days/week for 3 months, with a subsequent non-exposure period lasting 3 months. The rats were killed 1 week after the last exposure and additional post-exposure kills were performed at 1.5 and 3 months to monitor the progression of pulmonary change and fibre numbers in the lung. The assessments included bronchoalveolar lavage fluid (BALF) for evaluation of inflammatory response (e.g. protein content, enzymes, increase in polymorphonuclear leucocytes) and measurement of cell proliferation, assessment of early fibrosis through histological examination and comparison of body weight and lung lobe weights. After exposure of rats to the new biosoluble fibres no biologically significant effects were observed except that a statistically significant increase in lung weight was observed up to 1.5 months post-exposure in all three treatment groups. At 3 months post-exposure, the small increase was no longer significant. The increase in lung weight was still present in the MMVF21 group at the 3 months post-exposure kill. After 3 months exposure, lung retention of long fibres (length>20 microm) varied from 0.4 to 5.2 x 10(6) per lung for the biosoluble fibres. At 3 months post-exposure, the long fibre concentration in the lungs had decreased to 1-7% of this figure. The fibre with the relatively highest biopersistence (RIF41001) showed the highest fibre retention. The retention of the more biopersistent traditional stone wool MMVF21 was 5.7 x 10(6) per rat lung after 3 months exposure and had decreased to 64% of this figure at 3 months post-exposure. There was no clear difference in the bronchoalveolar lavage fluid cell concentration and percentage of cells between MMVF21 and the HT groups. Fibre inhalation caused a significant increase after 3 months in all the biochemical parameters measured in the BALF. Cell proliferation was enhanced at the end of exposure for MMVF21 for all three labelling indices, but only for the bronchiolar epithelium in the RIF41001 group and for alveolar parenchymal cells in the RIF43006-1 group. At the termination of the 3 month exposure period, as well as after 1.5 and 3 month recovery periods, minimal morphological changes were diagnosed in the biosoluble fibre groups. These changes included alveolar macrophage aggregation and/or microgranulomas at the bronchiolar-alveolar junction in the few rats affected. No fibrogenic potential was noted for any of the three fibres. No clear-cut difference between the different biosoluble fibre types was noted. In the MMVF21 group, minimal interstitial fibrosis was observed that gradually decreased after the 1.5 and 3 month non-exposure periods. In this study, the pathological changes found in the lungs of exposed rats were in accordance with the pathology previously reported from full lifespan inhalation studies. This may indicate that for fibres belonging to the man-made vitreous fibres group a well conducted biopersistence study is sufficient to predict possible pathogenic effects for new fibre types. The biological parameters examined in a 90 day study may indicate little additional information to contribute to the prediction of the outcome of carcinogenicity studies.
Rockwool International A/S, Hovedgaden 584, DK-2640 Hedehusene, Denmark. ole.kamstrup@rockwool.com
O
O
Kamstrup
A
A
Ellehauge
B
B
Bellmann
J
J
Chevalier
J M G
JM
Davis
D000280:Administration, Inhalation; D000535:Aluminum; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D008171:Lung Diseases / Q000473:pathology*; D008297:Male; D019016:Mineral Fibers; D023421:Models, Animal; D009784:Occupational Diseases / Q000473:pathology*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide; D012995:Solubility; D013997:Time Factors
D019016:Mineral Fibers; D012822:Silicon Dioxide; D000535:Aluminum