Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide

Our plain-English summary of Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide, by K. Donaldson, R.E. Bolton, A. Jones, et al (Thorax, 1988).

The study

• Authors: K. Donaldson, R.E. Bolton, A. Jones, G.M. Brown, M.D. Robertson, J. Slight, H. Cowie, J.M. Davis
• Journal: Thorax
• Published: 1988;43(7):525-33
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The kinetics of the bronchoalveolar response was assessed in rats exposed, at equal airborne mass concentration (10 mg/m3), to titanium dioxide--a non-pathogenic dust--and the two pathogenic mineral dusts quartz and chrysotile asbestos. Rats were killed at intervals over a 75 day exposure period and groups of rats exposed for 32 and 75 days after recovery for two months. Bronchoalveolar lavage was carried out and the lavage fluid characterised for cellular content, macrophage activation, and concentrations of free total protein, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase. Inhalation exposure to the two pathogenic dusts resulted in an increased number of leucocytes, macrophage activation, and increased levels of free enzymes and total protein. The pattern and magnitude of the responses to quartz and chrysotile differed. Chrysotile caused less inflammation than quartz, and the main cellular response peaked around the middle of the period of dust exposure whereas the highest levels of enzymes occurred towards the end. The difference in timing suggests that macrophages were not available for lavage towards the end of the exposure, owing to their playing a part possibly in deposition of granulation tissue. Quartz caused a greater cellular and enzyme response than chrysotile, particularly towards the end of the dust exposure phase. There was a noticeable progression of inflammation in the quartz exposed groups left to recover for two months, but not in the chrysotile recovery groups.

In plain English

This was an animal experiment at the Institute of Occupational Medicine, Edinburgh. Male PVG rats breathed air containing 10 mg/m3 of one of three dusts: titanium dioxide (used as an inert control), quartz, or UICC chrysotile asbestos. Exposure ran seven hours a day, five days a week, for up to 75 days. Groups of four rats were killed at set times during exposure. Other groups were removed after 32 or 75 days and kept for 62 days without dust before being killed. The researchers washed fluid through the lungs (bronchoalveolar lavage) and measured cells, protein and enzymes. Titanium dioxide brought no neutrophils into the lungs. Chrysotile and quartz both caused inflammation, but quartz produced much larger neutrophil numbers late in exposure. Inflammation in quartz-exposed rats increased after exposure stopped; this was not seen with chrysotile. Chrysotile-exposed rats developed diffuse lung fibrosis and quartz-exposed rats nodular fibrosis. The authors concluded that chrysotile did not produce the extent or progression of inflammation found with quartz.

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 inhalation experiment (rats exposed in inhalation chambers, with lung lavage at set time points and unexposed controls)
• Who was studied: Male specific pathogen free PVG rats bred at the Institute of Occupational Medicine, Edinburgh, aged 12 weeks at the start. Groups of four were killed after 2, 4, 8, 16, 32, 52 and 75 days of exposure. Further groups of four were removed after 32 and 75 days and kept 62 days before being killed. Two control rats were studied on each experimental day.
• Exposure: Airborne dust at 10 mg/m3 of titanium dioxide (rutile), quartz (Sikron F-600), or chrysotile asbestos (UICC standard sample "A"), for 7 hours a day, 5 days a week, up to 15 weeks (75 days). The authors state that UICC chrysotile at 10 mg/m3 produces about 2000 fibres/ml.
• Main results:
  • Titanium dioxide-exposed rats: macrophage numbers stayed at control levels throughout exposure, and no neutrophils were found in lavage fluid at any time.
  • Chrysotile-exposed rats: macrophages were twice as numerous as in controls by day 32 but had returned to control levels by 75 days.
  • Quartz-exposed rats: macrophage numbers rose fourfold between days 52 and 75. In rats exposed for 75 days and examined two months later, macrophage numbers were 10 times higher than in controls.
  • Both chrysotile and quartz caused significant increases in neutrophils compared with titanium dioxide from 16 days onwards, with much larger numbers seen with quartz. Quartz-exposed rats had 5.1 and 18.8 million neutrophils on days 52 and 75. Chrysotile neutrophil numbers never exceeded 3 million.
  • Quartz-exposed rats had more neutrophils in the 32 days plus recovery group (17.6 million) than in the 32 day group (0.8 million). In the chrysotile recovery groups, neutrophil numbers were smaller than in the matching groups that had not been allowed to recover.
  • Both chrysotile and quartz produced significantly more protein in the lavage fluid than titanium dioxide, from day 8 with chrysotile and from day 32 with quartz.
  • In chrysotile-exposed rats, cell numbers peaked around the middle of exposure, while free enzymes and protein were rising towards the end. The authors suggested that dust-laden macrophages may have become trapped in granulation tissue and so could not be washed out.
  • The proportion of lymphocytes was greater in chrysotile-exposed rats (mean 8.4, SEM 5.5) than in quartz-exposed rats (4.8, SEM 2.7) or titanium dioxide-exposed rats (3.8, SEM 2.6).
  • Inflammation in quartz-exposed rats increased during the two months of breathing normal air. In chrysotile-exposed rats there was no evidence of progression of inflammation after exposure stopped.
  • After prolonged exposure, chrysotile-exposed rats developed diffuse lung fibrosis and quartz-exposed rats developed nodular fibrosis.
• The authors' conclusion: The authors concluded that, taken together, the inflammatory measures showed that chrysotile does not produce the extent or progression of inflammation found with quartz. They also concluded that the patterns seen after inhalation differed from those reported in earlier studies that placed dust directly into the windpipe (intratracheal instillation).
• Limitations the authors state:
  • The lung weight to body weight ratio gave inconsistent results, and the authors concluded the method is not sufficiently sensitive.
  • An unexpectedly low level of macrophage spreading at 75 days with chrysotile may have been caused by an unidentified technical error.
  • No data were available for titanium dioxide-exposed rats on days 4 and 8.
  • The phagocytosis assay does not detect the total phagocytic potential of the macrophage population.
  • The large neutrophil response to quartz differs from human lavage findings, which the authors suggest may be due to the higher dose used experimentally.
  • Protein concentrations in control rats were initially high on days 2 and 4 for unknown reasons.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Bronchoalveolar Lavage (BAL), Macrophage, Lactate Dehydrogenase (LDH), Inflammation, Deposition.

Related studies

• Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz — J.M. Davis, A.D. Jones, et al. (1991)
• A spin label study of the effects of asbestos, quartz, and titanium dioxide dusts on the bovine erythrocyte membrane — W. Leyko, E. Gendek (1985)
• The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro — K. Donaldson, J. Slight, et al. (1988)
• Impaired chemotactic responses of bronchoalveolar leukocytes in experimental pneumoconiosis — K. Donaldson, G.M. Brown, et al. (1990)
• Acute biological effects of intratracheally instilled titanium dioxide whiskers compared with nonfibrous titanium dioxide and amosite in rats — Y. Ishihara, H. Kyono, et al. (1999)
• Pulmonary and pleural toxicity of potassium octatitanate fibers, rutile titanium dioxide nanoparticles, and MWCNT-7 in male Fischer 344 rats — M. Abdelgied, A.M. El-Gazzar, et al. (2019)

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