Rat lung reactivity to natural and man-made fibrous silicates following short-term exposure

Our plain-English summary of Rat lung reactivity to natural and man-made fibrous silicates following short-term exposure, by I. Lemaire, P.G. Dionne, D. Nadeau, et al (Environmental Research, 1989).

The study

• Authors: I. Lemaire, P.G. Dionne, D. Nadeau, J. Dunnigan
• Journal: Environmental Research
• Published: 1989;48(2):193-210
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The inflammatory and fibrogenic potential of three naturally occurring and two man-made industrial minerals were compared. Groups of five rats each received respectively a single intratracheal instillation of saline (control), UICC chrysotile B asbestos, short chrysotile 4T30, attapulgite, xonotlite (a calcium silicate), and Fiberfrax (an aluminum silicate) at doses of 1, 5, and 10 mg. One month after the treatment, assessment of lung morphology and bronchoalveolar lavage were performed on each animal. Under these conditions, UICC chrysotile B at all doses tested (1, 5, and 10 mg) induced fibrotic lesions in bronchiolar tissues while short chrysotile 4T30 (1, 5, and 10 mg) caused focal accumulation of inflammatory cells in the alveolar structures but no apparent fibrosis. Compared to these positive reactions with different fibrogenicity, xonotlite caused minimal inflammatory reactions detectable only at high dose (10 mg) and by bronchoalveolar analysis. By contrast, the rat lung reacted more significantly to attapulgite and Fiberfrax although the tissue reaction differed considerably for these two materials. While attapulgite, at doses up to 10 mg caused minimal reactions characterized by mononuclear cell infiltration mainly in the alveolar structures, Fiberfrax at 1 mg and higher caused significant granulomatous reactions and the appearance of early fibrosis. Overall the order of lung biological reactivity observed for the various silicates was xonotlite much less than attapulgite less than short chrysotile 4T30 less than Fiberfrax less than UICC chrysotile B. These observations indicate that Fiberfrax, attapulgite, and, to a lesser extent, xonotlite are biologically active within the time span studied and potentially deleterious for lung tissue.

In plain English

In this animal experiment, male Wistar rats each received a single dose placed directly into the windpipe, and their lungs were examined one month later. The authors compared UICC chrysotile B asbestos, a short chrysotile called 4T30, and three asbestos substitutes: attapulgite (a natural clay mineral), xonotlite (a man-made calcium silicate) and Fiberfrax (a man-made aluminum silicate). Saline-treated rats were controls, and 110 rats were examined in total. UICC chrysotile B (1 and 5 mg) caused fibrosis (scarring) of the small airways in every exposed rat. Fiberfrax caused granulomatous inflammation around the small airways in every rat at all doses. Areas of apparent early fibrosis were seen, though the authors said proof would require collagen staining. Short 4T30 chrysotile and attapulgite caused inflammation, and 4T30 caused no fibrosis. Xonotlite caused no tissue changes, only small increases in some inflammatory cells in lung washings at 10 mg. The authors ranked reactivity from highest to lowest: UICC chrysotile B, Fiberfrax, 4T30, attapulgite, xonotlite. They concluded that the three substitutes cannot be considered biologically inert, while cautioning that the results cannot be extrapolated to human exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: a single intratracheal instillation in rats, followed one month later by lung tissue examination and bronchoalveolar lavage (lung washing)
• Who was studied: Male Wistar rats weighing 250 to 300 g, from Charles River Canada. A total of 110 animals were examined (Table 2: 25 saline controls, and 5 or 10 rats per dose group). The research was done in Ottawa and Sherbrooke, Canada.
• Exposure: Single doses of 1, 5 or 10 mg, or saline. The materials were: UICC chrysotile B asbestos (58% of fibers shorter than 5 µm; tested at 1 and 5 mg); very short 4T30 chrysotile (100% shorter than 5 µm; average length 0.9 µm); attapulgite from the Quincy deposits, Florida (100% shorter than 1 µm; average 0.8 µm); xonotlite, trademark Promatek (100% shorter than 3 µm; average 1.2 µm); and a short fraction of Fiberfrax (50% shorter than 5 µm; average 8.3 µm).
• Main results:
  • UICC chrysotile B caused fibroblast proliferation and collagen deposition in the small airways (bronchiolitis obliterans, type D lesions) at both doses tested. Table 2 shows 5 of 5 rats affected at 1 mg and 5 of 5 at 5 mg.
  • UICC chrysotile B significantly increased the total number of cells recovered by lung washing: 14.9 million, compared with 9.2 million in saline controls.
  • Short 4T30 chrysotile caused interstitial inflammation (type B lesions) but no fibrosis at one month. Table 2 shows lesions in 2 of 5 rats at 1 mg, 7 of 10 at 5 mg, and 5 of 5 at 10 mg.
  • Xonotlite caused no significant changes in lung tissue at doses up to 10 mg. In lung washings, there were small but significant increases in neutrophils and lymphocytes, in the 10-mg group only.
  • Attapulgite fibers were found in the air sacs, surrounded by macrophages and epithelioid cells (type A lesions), at 1, 5 and 10 mg. Table 2 shows 5 of 5, 10 of 10, and 5 of 5 rats affected. Total cells in lung washings were 14.8 million at 5 mg and 15 million at 10 mg, compared with 9.2 million in controls.
  • Fiberfrax caused granulomatous lesions around the terminal bronchioles (type C lesions), with lymphocytes and giant cells, in all animals at all doses. At 10 mg, 4 of 5 rats had more extensive lesions. Areas of early fibrosis were seen in these lesions, but the authors noted that definitive proof would require collagen staining.
  • In lung washings from Fiberfrax-treated rats, neutrophils made up 14% of cells at 5 mg and 27% at 10 mg, and lymphocytes made up 5% and 4%.
  • Based on the tissue findings, the authors ranked lung reactivity from highest to lowest: UICC chrysotile B, Fiberfrax, short 4T30 chrysotile, attapulgite, and then xonotlite, which was much lower.
• The authors' conclusion: The authors concluded that attapulgite, Fiberfrax and xonotlite cannot be considered biologically inert. They added that, although the results cannot be extrapolated to human exposure, the possibility of harmful health effects from these widely used silicate fibers warrants special consideration.
• Limitations the authors state:
  • Definitive proof of the early fibrosis seen with Fiberfrax would require specific staining for collagen.
  • Only one month was studied. Longer follow-up is needed to learn whether the attapulgite and 4T30 lesions progress to fibrosis or resolve.
  • The results cannot be extrapolated to human exposure.
  • The Fiberfrax sample contained only 40% fibers.
  • Because xonotlite has a lower aspect ratio, fewer fibers per unit weight may have been given than for the other two short-fiber materials.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Silicate, Short-Term Exposure, Fibrogenic, UICC, Chrysotile, Palygorskite (Attapulgite), Bronchoalveolar Lavage (BAL), Fibrosis.

Related studies

• Cytotoxicity of respirable dusts from industrial minerals: comparison of two naturally occurring and two man-made silicates — D. Nadeau, L. Fouquette-Couture, et al. (1987)
• The biological reactivity of calcium silicate composites: in vivo studies — R.J. Richards, T.D. Tetley, et al. (1981)
• Biological reactivity of calcium silicate composites--in vitro studies — J. Hunt, F.D. Pooley, et al. (1981)
• The lung biological activity of American attapulgite — R. Bégin, S. Massé, et al. (1987)
• Mortality among a cohort of US man-made mineral fiber workers: 1985 follow-up — G.M. Marsh, P.E. Enterline, et al. (1990)
• Sister chromatid exchanges in rat pleural mesothelial cells treated with crocidolite, attapulgite, or benzo 3-4 pyrene — S. Achard, M. Perderiset, et al. (1987)

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