An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats

Our plain-English summary of An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats, by R.E. Bolton, J.H. Vincent, A.D. Jones, et al (British Journal of Industrial Medicine, 1983).

The study

• Authors: R.E. Bolton, J.H. Vincent, A.D. Jones, J. Addison, S.T. Beckett
• Journal: British Journal of Industrial Medicine
• Published: 1983;40(3):264-72
• Cited by: 77 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Two types of experiments were carried out to examine the effects of deposition and clearance on the accumulation in the lungs of rats of inhaled fibres of UICC amosite. In the first experiment the mass lung burdens of the dust in question were measured as a function of the time at which animals were killed after the cessation of the six week exposure period, and in the second the masses were measured for rats removed from exposure and killed at intervals during the exposure period itself. The experimental conditions were chosen to complement those of earlier work. Taken together with the results of that earlier work, the new results provide the basis for a simple mathematical model of the kinetics of deposition and clearance which appears to account for the major observed trends. Most significantly, there is strong evidence for an overload of clearance at high lung burdens (exceeding about 1500 micrograms/rat), in which a breakdown occurs of the intermediate rate clearance mechanisms (time constants of the order of 12 days). This hypothesis is supported for inhaled asbestos dust, quartz dust, and diesel fume by results obtained elsewhere. Biological explanations for the clearance overload hypothesis are at present speculative, involving discussion of the role of the macrophage in pulmonary clearance. It is believed that the clearance overload hypothesis could have possible consequences for people occupationally exposed to airborne dusts.

In plain English

This was an animal experiment. Groups of 48 male Wistar rats breathed UICC amosite asbestos dust for up to six weeks. Target respirable dust levels were 5, 10, 30 and 90 mg per cubic metre. Four experiments killed rats at intervals after exposure and measured the amosite left in their lungs. A fifth experiment removed rats weekly during exposure. Rats with lower lung burdens cleared dust quickly, then more slowly. Rats with higher burdens cleared it more slowly from the first measurement. The change came at lung burdens of 800 to 1500 micrograms. Rats exposed during their active period kept substantially more dust in their lungs. Examination of selected lungs showed no major structural changes. In tissue sections, the only widespread and consistent sign of exposure was dust-laden macrophages. A revised model with overload at an arbitrarily chosen lung burden of 1500 micrograms accounted substantially for gaps with long-term burdens measured in other studies. The authors concluded that their evidence supports the theory that lung burden itself can have a profound effect on particle clearance, but said the cause of overload is arguable.

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: five chamber exposure experiments measuring amosite lung burdens over time, combined with a mathematical model of deposition and clearance
• Who was studied: Outbred male SPF Wistar rats (AF/HAN strain), in groups of 48 for each of five experiments, killed in subgroups of eight; work done at the Institute of Occupational Medicine, Edinburgh
• Exposure: UICC amosite dust clouds in a 1 cubic metre chamber, for up to 210 hours over six weeks (7 hours a day, 5 days a week). Target respirable dust concentrations were 30 and 90 mg per cubic metre under normal daylight conditions, 5 and 10 mg per cubic metre under reverse daylight conditions, and 10 mg per cubic metre in a 'build-up' experiment. Measured averages were 28.4, 91.9, 6.0, 10.8 and 9.9 mg per cubic metre respectively.
• Main results:
  • In rats with low cumulative lung burdens, clearance was initially rapid but then slowed down.
  • In rats with high cumulative lung burdens, clearance was apparently slower from the first killing date.
  • The transition between the two clearance patterns occurred at a lung burden of 800 to 1500 micrograms.
  • In the amosite 90 experiment, the average total lung burden 3 days after exposure ended was 10091 plus or minus 1109 (standard error).
  • Lung burdens after reverse daylight exposure (rats active during dusting) were substantially greater than after the corresponding daylight exposure.
  • Histological examination of a representative selection of rat lungs showed no major structural changes.
  • The only widespread and consistent histopathological evidence of dust exposure was dust-laden macrophages in the lung tissue of all animals.
  • A kinetic model with normal clearance predicted long-term lung burdens that fell far short of those measured in other groups' long-term studies.
  • The authors revised the model to one possible version of clearance overload, starting at an arbitrarily chosen lung burden of 1500 micrograms. This version accounted substantially for the original discrepancy.
• The authors' conclusion: The authors concluded that their evidence supports the theory that lung burden itself can have a profound effect on particle clearance. They said it is arguable whether the overload is due to exceeding a critical lung burden, a high airborne dust concentration, or changes in deposition patterns.
• Limitations the authors state:
  • Detailed agreement between the model and the measurements was less satisfying. For example, the predicted difference between the amosite 30 and amosite 90 experiments was not seen in the measured data.
  • The authors said biological explanations for the overload are at present speculative.
  • Without more information on rat breathing patterns and regional deposition, the authors could not fully explain the reverse daylight results.
  • The authors said it is arguable whether overload results from a critical lung burden, a high airborne dust concentration, or physiologically mediated changes in deposition patterns.
  • Human evidence of clearance overload is difficult to obtain.

Topics

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

Medical terms in this study, explained in our Lexicon: UICC, Amosite, Deposition, Macrophage.

Related studies

• Kinetics of deposition and clearance of inhaled mineral dusts during chronic exposure — J.H. Vincent, A.M. Johnston, et al. (1985)
• Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers — D.B. Warheit, S.I. Snajdr, et al. (1997)
• Further observations on the short-term retention and clearance of asbestos by rats, using UICC reference samples — A.P. Middleton, S.T. Beckett, et al. (1979)
• Studies on the deposition of inhaled fibrous material in the respiratory tract of the rat and its subsequent clearance using radioactive tracer techniques. 1. UICC crocidolite asbestos — J.C. Evans, R.J. Evans, et al. (1973)
• Bromo-deoxyuridine (BRDU) uptake in the lungs of rats inhaling amosite asbestos or vitreous fibres at equal airborne fibre concentrations — K. Donaldson, D.M. Brown, et al. (1995)
• Clearance and dimensional changes of crocidolite asbestos fibers isolated from lungs of rats following short-term exposure — V.L. Roggli, M.H. George, et al. (1987)

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