Determinants of the pathogenicity of man-made vitreous fibers (MMVF)

Our plain-English summary of Determinants of the pathogenicity of man-made vitreous fibers (MMVF), by G. Oberdörster (International Archives of Occupational and Environmental Health, 2000).

The study

• Author: G. Oberdörster
• Journal: International Archives of Occupational and Environmental Health
• Published: 2000;73 Suppl:S60-8
• Type of article: Review
• Cited by: 75 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction And Objectives: A number of man-made vitreous fibers (MMVF) have been developed over the years to replace asbestos fibres in its uses as insulating material. Concerns have been raised that these man-made fibers may also pose a significant health hazard when inhaled during their manufacture and application. As will be discussed in this brief overview, dose, dimension and durability of fibrous particles are key parameters with respect to the induction of adverse pulmonary effects, including carcinogenicity as well as non-cancer effects. In particular, fiber biopersistence plays a most important role for pulmonary pathogenicities, and consequently biopersistence receives greatest attention in the search of new fibrous materials.

Methods And Results: Tests to evaluate fiber biopersistence include the administration of fibers by a short-term inhalation (5 days) or intratracheal instillation into rats. Advantages of the inhalation methodology include the even distribution throughout the lung administered by a physiological process. A disadvantage of this method is the limited respirability of long fibers in the rat whereas they are well respirable by humans. Such long fibers ( > 20 microm) have the greatest potential for tumorigenicity and need special consideration in connection with the evaluation of fiber biopersistence. Enrichment of the inhaled aerosol by these long fibers needs to be considered in order to deposit enough of them in the lower respiratory tract of the rat. In contrast, the advantage of the instillation technique is that these long fibers can be delivered to the lung. However, the major disadvantages of intratracheal instillations are the potential of the administered fibers to form clumps and aggregates in the airways and the induction of a major inflammatory response when high-bolus doses are administered. This could influence fiber dissolution in the lungs significantly.

Conclusions: At the same delivered lung dose, a fiber of low biopersistency has the least effect and is, therefore, less likely to induce lung or pleural tumors even under chronic exposure conditions. Respective animal studies with more fibers of different biopersistence have confirmed this general principle. It is very important that, when evaluating and interpreting fiber effects observed in experimental animals, species differences with respect to respirability, lung retention and mechanisms of responses are considered.

In plain English

This article was an overview, presented at a 1999 congress, of what makes man-made vitreous fibers (MMVF) harmful to the lungs. These fibers were developed to replace asbestos as insulation. It mainly reviewed rat studies by other researchers rather than reporting one new study. The author discussed fiber dose, dimension and durability, with emphasis on biopersistence, which also includes the lung's own clearance. The reviewed work indicated that, other factors being equal, fibers longer than about 15 to 20 micrometers were the most critical predictor of tumors. In one cited rat study, a low injected dose of long chrysotile increased peritoneal tumors, while the same dose of short chrysotile caused no response. Cited rat data showed long amosite fibers staying in the lung far longer than soluble fibers. The author compared two rat tests of fiber persistence, short-term inhalation and intratracheal instillation, describing drawbacks of each. The author concluded that, at the same delivered lung dose, a low-biopersistence fiber is less likely to cause lung or pleural tumors. The author added that rat-human differences must be considered.

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: Brief narrative overview (review) of mainly animal studies by other researchers, presented at the Medichem 1999 congress
• Who was studied: Mainly rats in the reviewed experiments (inhalation, intratracheal instillation and intraperitoneal injection studies); no human study population
• Exposure: Man-made vitreous fibers (including MMVF-10, MMVF-21, MMVF-34, MMVF-0 and B-01-0.9), refractory ceramic fibers, carbon fibers, and asbestos for comparison (amosite, crocidolite, chrysotile); focus on fiber dose, length and biopersistence, especially fibers longer than 20 micrometers
• Main results:
  • In a cited 2-year inhalation study of refractory ceramic fibers in rats (Mast et al. 1995), exposures ranged from 36 to 234 fibers/cm3. Only the highest exposure concentration produced a significant tumor response; the lower concentrations did not differ significantly from controls.
  • In a cited intraperitoneal injection study in rats (Davis and Jones 1988), a relatively low dose of long chrysotile significantly increased tumor incidence in the peritoneal cavity, while the same dose of short chrysotile induced no response. At a 100-fold higher dose, both preparations gave a near maximal tumor response.
  • From the reviewed studies, the author judged that the presence of fibers longer than 15 to 20 micrometers is the most critical predictor of tumor-causing ability, other factors being equal.
  • Using data from Bernstein et al. 1996, the article reported that in vitro dissolution rates at pH 7.4 correlated with lung retention halftimes of fibers longer than 20 micrometers in rats, but not very strongly. The correlation at pH 4.5 was even less satisfactory.
  • For amosite in rats after 5-day inhalation (Hesterberg et al. 1998), 65% of the deposited fiber dose was cleared quickly. The weighted retention halftime was 418 days, while the slow-phase halftime was 1160 days.
  • In tabulated rat data (Pott and Roller 1998), retention halftimes after intratracheal instillation were generally greater than those after inhalation.
  • A summary table (partly based on Hesterberg 1998) showed MMVF-induced lung pathology correlating with longer slow-phase retention halftimes of fibers longer than 20 micrometers. Amphiboles had extremely long halftimes and more severe lung pathology. For chrysotile the picture was not clear-cut: reported halftimes for long fibers appeared rather short, yet its pathogenicity did not differ from the amphiboles.
  • In a 5-day rat inhalation study described in the article (no citation given), lung burdens of total fibers were similar. Despite long biopersistence, carbon fibers produced an inflammatory response not different from MMVF-10 and significantly less than amosite throughout the post-exposure period.
• The authors' conclusion: The author concluded that dose, dimension and durability are key determinants of MMVF effects, with biopersistence playing a most important role. At the same delivered lung dose, a fiber of low biopersistence has the least effect and is less likely to induce lung or pleural tumors. Species differences in respirability, lung retention and response mechanisms must be considered when interpreting animal results.
• Limitations the authors state:
  • Human data on MMVF pathogenicity are mostly insufficient, so animal studies are relied on.
  • Long fibers are poorly respirable by rats although well respirable by humans, which limits the rat inhalation test.
  • The determinants discussed may not apply to all man-made fibers, such as certain organic fibers.

Topics

Medical terms in this study, explained in our Lexicon: Vitreous, biopersistence.

Related studies

• Cytotoxic and oxidative effects induced by man-made vitreous fibers (MMVFs) in a human mesothelial cell line — D. Cavallo, A. Campopiano, et al. (2004)
• The thermal transformation of Man Made Vitreous Fibers (MMVF) and safe recycling as secondary raw materials (SRM) — A.F. Gualtieri, E. Foresti, et al. (2009)
• Potential pulmonary effects of man-made organic fiber (MMOF) dusts — D.B. Warheit, G.A. Hart, et al. (2001)
• Comparison of cytotoxicity of man-made vitreous fibres — K. Luoto, M. Holopainen, et al. (1997)
• Man-made respirable-sized organic fibers: what do we know about their toxicological profiles? — D.B. Warheit, K.L. Reed, et al. (2001)
• Synthetic vitreous fibers: a review of toxicology research and its impact on hazard classification — T.W. Hesterberg, G.A. Hart (2001)

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