Lung Biopersistence and in Vitro Dissolution Rate Predict the Pathogenic Potential of Synthetic Vitreous Fibers

Our plain-English summary of Lung Biopersistence and in Vitro Dissolution Rate Predict the Pathogenic Potential of Synthetic Vitreous Fibers, by T.W. Hesterberg, G.A. Hart (Inhalation Toxicology, 2000).

The study

• Authors: T.W. Hesterberg, G.A. Hart
• Journal: Inhalation Toxicology
• Published: 2000;12 Suppl 3:91-7
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Here we review the past decade of research on inorganic fiber toxicology, which demonstrates that fiber biopersistence and in vitro dissolution rate correlate well with fiber pathogenicity. Test fibers for these studies included eight synthetic vitreous fibers (SVFs)-refractory ceramic fiber (RCF1), four fiber glasses (FCs), rock wool, slag wool, HT stone wool-and two asbestos types (crocidolite and amosite). Fiber toxicology and biopersistence were investigated using rodents exposed by inhalation. To evaluate chronic inhalation toxicity, rodents were exposed nose-only to ∼ 100 fibers >20 µm in length (F > 20 µm)/cm(3), 6 h/day, 5 days/wk, for 2 yr (rats) or 1½ yr (hamsters). To evaluate lung biopersistence, rats were exposed nose-only for 5 days to fiber aerosol; lung burdens were then analyzed during 1 yr postexposure. In vitro dissolution rate was evaluated in a flow-through system using physiological solutions that mimic the inorganic components of extra- and intracellular lung fluids. The 10 test fibers encompassed a range of respiratory toxicities, from transient inflammation only to carcinogenesis. Lung clearance weighted half-times (WT½) for F > 20 µm were 6-15 days for stonewool, building insulation FCs, and slag wool; 50-80 days for rock wool, 2 special-application FCs, and RCFI; and >400 days for asbestos. WT½ correlated with pathogenicity: The rapidly clearing fibers were innocuous (insulation FCs, slag wool, and stonewool), but the more biopersistent fibers were fibrogenic (rock wool) or fibrogenic and carcinogenic (special-application FCs, RCFI, amosite and crocidolite asbestos). In vitro dissolution rates (k dis= ng/cm(2)/h) of the 10 fibers at pH 7.4 or 4.5 ranged from < 1 to >600. Fibers that dissolved rapidly in vitro also cleared quickly from the lung and induced only transient inflammation in the chronic studies. In contrast, fibers that dissolved slowly in vitro were biopersistent in the lung and tended to induce permanent pathogenicity. Other in vitro studies of fiber degradation suggest that, in addition to fiber dissolution, fiber leaching and subsequent transverse breakage may also be important mechanisms in lung biopersistence and hence pathogenicity. The validity of using lung biopersistence for predicting the potential pathogenicity of SVFs is confirmed by this research. The research also supports the use of in vitro fiber degradation at pH 7.4 and/or pH 4.5 as an indicator of SVF potential pathogenicity.

In plain English

This article reviewed rodent research on synthetic vitreous fibers (fiberglass, mineral wools, refractory ceramic fiber) and amosite and crocidolite asbestos. Rats inhaled fibers for 2 years and hamsters for 18 months (JM E glass, 1 year) to study disease; rats inhaled fibers for 5 days to study lung persistence. Building-insulation fiberglasses, slag wool and HT stone wool caused only inflammation that subsided, with weighted lung-clearance half-times of 6 to 15 days for fibers longer than 20 µm. Rock wool caused lung fibrosis but no tumors. Two special-application fiberglasses and RCF1 caused fibrosis and thoracic cancer (half-times 49 to 79 days), though a table footnote marked JM 475 glass as possibly tumorigenic in hamsters but not rats. Both asbestos types caused fibrosis and thoracic cancer, had half-times of 418 (amosite) and 817 days (crocidolite), and dissolved slowest in simulated lung fluid at pH 7.4. In one hamster study, amosite caused 17 mesotheliomas (about 100 animals at risk) and JM 475 glass caused 1. The authors concluded that lung biopersistence predicts these fibers' potential pathogenicity, while noting inconsistencies with pH 7.4 dissolution rates.

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: Review of the authors' and colleagues' earlier rodent inhalation, lung biopersistence and in vitro fiber dissolution studies
• Who was studied: Rats and hamsters in chronic inhalation studies of twelve synthetic vitreous fiber compositions and three asbestos types. Rats in biopersistence studies of eight synthetic vitreous fibers and two asbestos types.
• Exposure: Nose-only inhalation of several fiber types: rock wool, slag wool and HT stone wool; building-insulation fiberglasses (JM 901, CertainTeed); special-application fiberglasses (JM 475, JM E glass); refractory ceramic fiber (RCF1); and amosite and crocidolite asbestos. Chronic exposure was 6 h/day, 5 days/wk for 2 yr in rats or 18 months in hamsters. JM E glass was instead given 5 h/day, 7 days/wk for 1 yr. Biopersistence exposure was 5 days in rats.
• Main results:
  • Building-insulation fiberglasses (901 and CT), slag wool and HT stone wool induced only inflammation, which subsided after exposure ended.
  • Rock wool induced interstitial lung fibrosis but no tumors.
  • The results text reported that JM 475 and E glass special-application fiberglasses, RCF1, and amosite and crocidolite asbestos induced lung fibrosis and thoracic cancer (lung cancer and/or mesothelioma).
  • A Table 1 footnote, which by its position in the table appears to apply to JM 475 glass, qualified its tumor finding as possibly tumorigenic in hamsters but not in rats.
  • In the 18-month hamster study, amosite asbestos induced fibrosis and 17 mesotheliomas, with about 100 animals at risk. JM 475 fiberglass induced lung fibrosis and 1 mesothelioma. JM 901 glass induced no fibrosis or tumors.
  • In the hamster study, after 18 months the number of fibers per lung for 901 glass was one-fifth that of 475 glass and one-thirtieth that of amosite.
  • Weighted lung-clearance half-times in rats for fibers longer than 20 µm were 6-15 days for 901 FG, CT FG, slag wool and HT stone wool. They were 49-79 days for rock wool, 475 and E glass, and RCF1. They were more than 400 days for amosite (418) and crocidolite (817).
  • Dissolution rate constants at pH 7.4 were 59-400 ng/cm2/h for building-insulation fiberglasses, slag wool and HT stone wool. They were 3-20 for the two special-application fiberglasses and RCF1, and less than 1 for the two asbestos types.
  • HT stone wool had a relatively low dissolution rate at pH 7.4 but a high rate at acidic pH 4.5.
  • In vitro, many synthetic vitreous fibers underwent leaching rather than simple dissolution and then broke crosswise into shorter segments.
• The authors' conclusion: The authors concluded that this research confirms lung biopersistence as a valid predictor of the potential pathogenicity of synthetic vitreous fibers. They added that it also supports in vitro fiber degradation at pH 7.4 and/or pH 4.5 as an indicator.
• Limitations the authors state:
  • The authors noted inconsistencies in the inverse relationship between lung clearance half-time and dissolution rate at pH 7.4. They suggested that biopersistence is not simply a matter of dissolution in neutral lung fluid.

Topics

Medical terms in this study, explained in our Lexicon: biopersistence, Vitreous, Crocidolite, Amosite, Inflammation, Carcinogenesis, Fibrogenic, Carcinogenic.

Related studies

• Differential in vitro cellular response induced by exposure to synthetic vitreous fibers (SVFs) and asbestos crocidolite fibers — G. Cardinali, D. Kovacs, et al. (2006)
• Synthetic vitreous fibers: a review of toxicology research and its impact on hazard classification — T.W. Hesterberg, G.A. Hart (2001)
• An experimental approach to the evaluation of the biopersistence of respirable synthetic fibers and minerals — D.M. Bernstein, R. Mast, et al. (1994)
• Biopersistences of man-made vitreous fibers and crocidolite fibers in rat lungs following short-term exposures — R.P. Musselman, W.C. Miiller, et al. (1994)
• Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats — T.W. Hesterberg, W.C. Miiller, et al. (1994)
• In vitro cytotoxicity of asbestos and man-made vitreous fibers: roles of fiber length, diameter and composition — G.A. Hart, L.M. Kathman, et al. (1994)

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