Chronic inhalation studies of man-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs

Our plain-English summary of Chronic inhalation studies of man-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs, by T.W. Hesterberg, W.C. Miiller, P. Thevenaz, et al (The Annals of Occupational Hygiene, 1995).

The study

• Authors: T.W. Hesterberg, W.C. Miiller, P. Thevenaz, R. Anderson
• Journal: The Annals of Occupational Hygiene
• Published: 1995;39(5):637-53
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhalation studies were conducted to determine the chronic biological effects in rodents of respirable fractions of different man-made vitreous fibres (MMVFs), including refractory ceramic fibre (RCF), fibrous glass, rock (stone) wool and slag wool. Animals were exposed nose-only, 6 h per day, 5 days per week, for 18 months (hamsters) or 24 months (rats). Exposure to 10 mg m-3 of crocidolite or chrysotile asbestos induced pulmonary fibrosis, lung tumours and mesothelioma in rats, thus validating the inhalation model with known human carcinogenic fibres. Exposure of rats to 30 mg m-3 of refractory ceramic fibres (RCF) also resulted in pulmonary fibrosis as well as significant increases in lung tumours and mesothelioma. In hamsters, 30 mg m-3 of RCF induced a 41% incidence of mesotheliomas. Exposure of rats to 30 mg m-3 of fibre glasses (MMVF 10 or 11) or of slag wool (MMVF 22) was associated with an inflammatory response, but no mesotheliomas or significant increase in the lung tumours were observed. Rock wool (stone wool: MMVF 21) at the same exposure level resulted in minimal lung fibrosis, but no mesotheliomas or significant increase in the lung tumours were observed. Fibre numbers (WHO fibres) and dimensions in the aerosols and lungs of exposed animals were comparable in this series of inhalation studies. Differences in lung fibre burdens and lung clearance rates could not explain the differences observed in the toxicologic effects of the MMVFs. These findings indicate that dose, dimension and durability may not be the only determinants of fibre toxicity. Chemical composition and the surface physico-chemical properties of the fibres may also play an important role.

In plain English

This paper summarized and compared a series of animal inhalation experiments begun in 1988 in Geneva. Male rats and hamsters breathed fibres nose-only, 6 hours a day, 5 days a week. Rats were exposed for 24 months to a refractory ceramic fibre (RCF 1), two fibre glasses (MMVF 10 and 11), rock wool (MMVF 21) or slag wool (MMVF 22). The paper compared these only at the highest dose, 30 mg per cubic metre. Control animals breathed filtered air or 10 mg per cubic metre of chrysotile or crocidolite asbestos. In rats, each asbestos type induced one mesothelioma and significant increases in lung tumours. RCF 1 induced two mesotheliomas and a significant increase in lung tumours (16 rats, 13.0%). Rock wool produced minimal fibrosis. Rock wool, slag wool and the two fibre glasses produced no mesotheliomas and no significant lung tumour increases. In hamsters exposed for 18 months, RCF 1 induced mesotheliomas in 42 animals (41%), and chrysotile induced fibrosis but no tumours. The authors concluded that fibre dose, size and durability may not be the only determinants of fibre toxicity.

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 paper summarizing and comparing a series of chronic (long-term) nose-only inhalation studies in rodents. It focused on fibre characteristics in the exposure air and in the lungs. Detailed methods and results of the individual studies were published elsewhere.
• Who was studied: Six-week-old male Fischer 344/N rats and Syrian golden hamsters, studied at Research and Consulting Company in Geneva, Switzerland, starting in mid-1988. There were 140 animals in each fibre-exposed group and each filtered-air control group. After exposure ended, animals were held until about 20% were still alive.
• Exposure: Size-selected respirable man-made vitreous fibres: kaolin-based refractory ceramic fibre (RCF 1), two fibre glasses (MMVF 10 and 11), rock (stone) wool (MMVF 21) and slag wool (MMVF 22). This paper compared them at 30 mg per cubic metre. Positive controls breathed 10 mg per cubic metre of chrysotile or crocidolite asbestos. Exposure was nose-only, 6 h per day, 5 days per week. It lasted 24 months in rats and 18 months in hamsters, which received RCF 1 or chrysotile. Crocidolite exposure in rats was stopped at 10 months because of excess deaths.
• Main results:
  • In rats, chrysotile and crocidolite asbestos each induced a single mesothelioma and significant increases in lung tumours. Chrysotile: 13 lung tumours (18.9%) and 1 mesothelioma (1.4%). Crocidolite: 15 lung tumours (14.2%) and 1 mesothelioma (0.9%).
  • In rats exposed to RCF 1, minimal pulmonary fibrosis appeared after 6 months. RCF 1 induced two mesotheliomas and lung tumours in 16 rats (13.0%). The authors marked this lung tumour rate as significantly above air controls (p less than 0.05).
  • In rats, rock wool (MMVF 21) produced minimal lung fibrosis after 18 months of exposure. It induced no mesotheliomas and no significant increase in lung tumours (5 rats, 4.4%).
  • In rats, the fibre glasses (MMVF 10 and 11) and slag wool (MMVF 22) produced no pulmonary fibrosis, no mesotheliomas and no significant increase in lung tumours compared with unexposed controls. Lung tumours numbered 7 (5.9%), 3 (2.7%) and 3 (2.6%) respectively. All five man-made fibres produced an inflammatory response after 3 months.
  • In hamsters, RCF 1 induced pulmonary fibrosis and mesotheliomas in 42 animals (41%), but no lung tumours. Chrysotile asbestos induced pulmonary fibrosis in hamsters but no mesotheliomas or lung tumours.
  • Of the five man-made fibres, the RCF 1 aerosol had the lowest number of WHO fibres per cubic centimetre (187 plus or minus 53). Even so, RCF 1 was the only one that produced an elevation in lung tumours and mesothelioma.
  • In rat lungs, numbers of WHO fibres and of fibres longer than 10 micrometres were comparable across the five man-made fibres. Counts of fibres longer than 20 micrometres were higher at later time points for RCF 1 and rock wool (MMVF 21) than for the other fibre types.
  • After exposure stopped, the two fibre glasses took longer to clear from the lung than RCF 1, counting WHO fibres and fibres longer than 10 micrometres. Long fibres (over 20 micrometres) cleared faster than shorter fibres. RCF 1 and rock wool cleared at similar rates.
• The authors' conclusion: The authors concluded that differences in lung fibre burdens and clearance did not explain the differences in toxicity between the man-made fibres. In their view, fibre dose, dimension and durability may not be the only determinants of fibre toxicity. They suggested that chemical composition and surface properties may also play a role.
• Limitations the authors state:
  • The RCF 1 aerosols contained 5- to 10-fold more non-fibrous particles than those of the other man-made fibres. The authors stated that the effect of this on RCF's results was not yet known.
  • The paper compared fibre characteristics only at the highest dose (30 mg per cubic metre). Lower doses were left for another paper.
  • The asbestos fibres had very different average dimensions from the man-made fibres. For that reason, the authors stated it was not appropriate to compare them fibre by fibre.
  • The authors stated that more studies are needed to determine whether a fibre's ability to be leached is a critical determinant of its toxicity.

Topics

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

Medical terms in this study, explained in our Lexicon: Vitreous, Respirable Fraction, Crocidolite, Chrysotile, Pulmonary Fibrosis, Mesothelioma, Carcinogenic, Fibrosis.

Related studies

• 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)
• Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats — T.W. Hesterberg, W.C. Miiller, et al. (1993)
• Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the syrian golden hamster. Part I. Results of a subchronic study and dose selection for a chronic study — T.W. Hesterberg, C. Axten, et al. (1999)
• Natural mineral fibers: conducting inhalation toxicology studies - part A: Libby Amphibole aerosol generation and characterization method development — A. Wang, A. Gupta, et al. (2023)
• Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure — E.E. McConnell, C. Axten, et al. (1999)
• Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats — C. Schürkes, W. Brock, et al. (2004)

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