The advantages and limitations of an in vivo test system for investigating the cytotoxicity and fibrogenicity of fibrous dusts

Our plain-English summary of The advantages and limitations of an in vivo test system for investigating the cytotoxicity and fibrogenicity of fibrous dusts, by S.E. Sykes, A. Morgan, S.R. Moores, et al (Environmental Health Perspectives, 1983).

The study

• Authors: S.E. Sykes, A. Morgan, S.R. Moores, W. Davison, J. Beck, A. Holmes
• Journal: Environmental Health Perspectives
• Published: 1983;51:267-73
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The acute response of the rat lung to a range of fibrous materials has been investigated by bronchopulmonary lavage, at dose levels of 0.5 and 1.0 mg, 1 and 7 days after their administration by intratracheal instillation. The materials chosen for study included UICC chrysotile A, amosite, crocidolite and anthophyllite, and samples of S. African "long" amosite and glass fiber. In addition, the subacute response to 1, 2 and 3 mg of chrysotile and amosite has been studied at 50 and 100 days after instillation. In the acute phase at 1 day after instillation, the response to chrysotile was greater than that to any of the other materials, but by 7 days there was no gradation in the response to different dusts. In the subacute phase, cell recoveries were low, and it was not possible to assess the long-term cytotoxic or fibrogenic effects of amosite and chrysotile by analyses of lung washes, even though biochemical and histological methods indicated gross changes in lung pathology.

In plain English

This animal experiment tested whether putting fibrous dusts into rats' windpipes and then washing out the lungs (lavage) could measure their harm. In short-term tests, rats received UICC chrysotile A, amosite, crocidolite or anthophyllite (0.5 or 1.0 mg), South African "long" amosite (0.5 mg only) or glass fiber (1.0 mg only), examined 1 and 7 days later. Longer tests gave 1, 2 or 3 mg of chrysotile or amosite, with follow-up to 100 days; long amosite was used at 1 and 2 mg, but at 3 mg there was significant mortality, so UICC amosite was used instead. At 1 day, chrysotile gave the greatest response; very little response to anthophyllite, crocidolite or glass fiber was detected. With 3 mg of chrysotile or UICC amosite, lung hydroxyproline content more than doubled compared with controls by 100 days. Microscopy showed nodules in the small airways and alveolar ducts. The authors concluded that the method was useful for immediate cell damage but did not appear adequate for assessing long-term effects. They suggested that lavage sampled only limited areas of the lung.

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: dusts given to rats by intratracheal instillation, with lung responses measured by bronchopulmonary lavage, lung biochemistry and histology
• Who was studied: An inbred strain of rats from the MRC Radiobiological Unit, Harwell, studied at the Atomic Energy Research Establishment, Harwell, Oxfordshire, UK. The article does not state the number of animals or the study dates.
• Exposure: Short-term study: UICC chrysotile A, amosite, crocidolite and anthophyllite were each given at 0.5 mg and at 1.0 mg. Cape South African "long" amosite (average fiber length 117 micrometres) was given at 0.5 mg only, and glass fiber at 1.0 mg only. Subacute study: chrysotile and amosite were given at 1, 2 and 3 mg, with each dose split into three instillations over one week. For amosite, long amosite was used at 1 and 2 mg; at 3 mg there was significant mortality, so the UICC amosite sample was used at that dose instead.
• Main results:
  • At 1 day after instillation, the acute response was greatest for chrysotile.
  • At 1 day, very little response to anthophyllite, crocidolite or glass fiber was detected. The effects of anthophyllite and glass fiber on lung weight were not significant compared with saline controls.
  • At the 0.5 mg dose, long amosite caused a much larger influx of polymorphonuclear leukocytes (PMN) than the same dose of UICC amosite.
  • There was no significant increase in alveolar macrophage numbers for any material at 1 or 7 days.
  • In the subacute study, PMN numbers for chrysotile and amosite showed no evidence of time or dose dependence.
  • In the subacute study, LDH levels in lavage fluid were elevated compared with saline controls in all cases. The response to amosite was consistently greater than that to chrysotile.
  • In the lung homogenate measurements, shown for 3 mg of chrysotile or amosite (UICC amosite at that dose), lung hydroxyproline content had more than doubled compared with control values by 100 days.
  • Histology showed nodules, mainly in the bronchioles and alveolar ducts, for all doses of chrysotile. Similar nodules occurred with amosite and were very large in rats given 2 mg of long amosite.
• The authors' conclusion: The authors concluded that instillation and lavage proved useful for investigating the immediate cytotoxicities of fibrous dusts in rats but did not appear adequate for assessing long-term effects. They suggested the difficulties may lie more with lavage than with instillation. They also judged long amosite the most fibrogenic of the materials tested.
• Limitations the authors state:
  • In the subacute study, lavage appeared to sample only limited areas of the lung, so it gave no real assessment of the processes going on in the lung.
  • Accumulations of fibers and cells in the bronchioles and alveolar ducts may block areas of the lung so that lavage does not sample them effectively.
  • The amosite results were complicated because long amosite could not be used at the top dose of 3 mg.

Topics

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

Medical terms in this study, explained in our Lexicon: UICC, Chrysotile, Amosite, Crocidolite, Anthophyllite, Fibrogenic, Pathology.

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