Asbestos as reference material for fibre-induced cancer

Our plain-English summary of Asbestos as reference material for fibre-induced cancer, by H. Muhle, F. Pott (International Archives of Occupational and Environmental Health, 2000).

The study

• Authors: H. Muhle, F. Pott
• Journal: International Archives of Occupational and Environmental Health
• Published: 2000;73 Suppl:S53-9
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The objective of this paper is to review published data on the carcinogenicity of asbestos fibres with regard to the elucidation of a potential risk originating from exposure to man-made vitreous fibres (MMVF). Steps in the comparison of the two fibre classes are characterization of the fibres, pulmonary deposition, biodurability and biopersistence and a review of the cancer risk from asbestos fibres after inhalation in rats and humans. Various dust samples of chrysotile, crocidolite, and amosite were used as reference materials in studies with experimental animals. These fibres are normally thinner and shorter than MMVF. These differences in dimensions cause differences in the deposition in the airways. In addition, significant dissimilarities exist in the deposition pattern between rats and humans. Data from biopersistence studies show that focusing only on fibres longer than 20 microm and using weighted half-time for a characterization of risk may be misleading. Inhalation experiments with rats need fibre exposure concentrations over 100 times higher to match the lung cancer risk of asbestos workers, and about 1,000 times higher to reach the same mesothelioma risk. Also, the striking difference between the low lung burden of amphibole fibres of asbestos workers with mesothelioma and the more than 1,000 times higher lung burden of rats with a low mesothelioma risk demonstrates the low sensitivity of the inhalation test model for the carcinogenic potency even of crocidolite fibres. It can be concluded that the rat inhalation model is also not sensitive enough to predict the cancer risk of other fibre types for humans.

In plain English

This review asked how well asbestos serves as a reference for man-made vitreous fibres and how well rats predict human risk. Among workers outside mining and milling, 25 years at 1 fibre per ml (fibres over 5 micrometres, light microscopy) was linked with about 2.5% average excess risk of lung cancer or mesothelioma death before age 80. Rats, mostly exposed for 1 year, needed over 100 times (about 250 times) higher concentrations, measured the same way, for similar tumour risks. Workers at 2 amphibole fibres per ml for 25 years had about 2% mesothelioma risk; rats were expected to reach that only at nearly 1000-fold concentrations for 1 year, 35 hours weekly. In one crocidolite rat study, stopped after 10 months, lungs held 1850 WHO-dimension fibres per microgram of dry lung at 1 year. A human mesothelioma case-control study found a significant odds ratio of about 5 at 0.1 to 0.2 WHO-dimension amphibole fibres per microgram of dry lung. The authors concluded the rat has very low sensitivity, at least for crocidolite, and false-negative EU test results are very probable.

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: Review of published data (human epidemiology and rat inhalation studies of asbestos)
• Who was studied: Published epidemiologic studies of asbestos workers and published chronic inhalation experiments in rats (Wistar and Fischer strains). The worker dose-response curve used for comparison excluded mining and milling.
• Exposure: Asbestos fibres (chrysotile and the amphiboles amosite, crocidolite, tremolite), compared as reference materials with man-made vitreous fibres
• Main results:
  • Asbestos workers outside mining and milling, from the dose-response curve based on earlier studies: exposure to 1 fibre per ml for 25 years was associated with an average excess tumour risk of about 2.5%. Fibres were those longer than 5 micrometres, measured by light microscopy. The underlying curve concerned asbestos-induced deaths from lung cancer or mesothelioma before age 80 after exposure from age 20 to 45.
  • Rats: in the majority of the chronic inhalation experiments, exposure was 35 hours per week for 1 year. To cause tumour risks similar to those of workers exposed for 25 years, fibre concentrations had to be more than 100 times (about 250 times) higher, measured with the same method as in the workplace. The difference was higher when rat chamber concentrations were measured by electron microscopy.
  • Mesothelioma in rats after high inhalation exposure to amphiboles (500 to 2000 WHO fibres per ml) totalled 6 of 342 rats (1.8%). Workers exposed to 2 amphibole fibres per ml for 25 years had a mesothelioma risk of about 2%. The same risk in rats would be expected only at a nearly 1000-fold fibre concentration for 1 year, 35 hours per week.
  • In the crocidolite study of McConnell et al. (1994) in Fischer rats, 14 of 106 rats (13.2%) that survived the second year or longer died with a lung tumour
  • In that rat study, exposure was stopped after 10 months because of unexpected mortality. At 1 year, the lungs held 1850 fibres with WHO dimensions per microgram of dry lung. The count was 759 after the second year without further exposure. One passage of the article describes the 1850 figure as 'after 12 months exposure'.
  • Humans: in a study of mesothelioma cases and controls summarized by Rödelsperger and Woitowitz, a significant odds ratio of about 5 was found at amphibole concentrations of 0.1 to 0.2 fibres per microgram of dry lung tissue. These were WHO-dimension fibres counted by electron microscopy.
  • In a rat biopersistence study of amosite (Hesterberg et al. 1998), the half-time for fibres longer than 20 micrometres was 20 days for the fast pool and 1160 days for the slow pool
  • The authors stated that the combined effect of smoking and asbestos could explain only about a ten-fold part of the high lung cancer risk in workers. They hypothesized that the much higher number of cells at risk and of cell generations in humans may partly explain the species difference.
• The authors' conclusion: The authors concluded that the rat shows very low sensitivity for detecting the cancer-causing potency of crocidolite fibres, at least, and that false-negative results with the EU test method for mineral fibres are very probable
• Limitations the authors state:
  • The authors questioned whether it is adequate to compare tumour response in small rat lungs after little more than 2 years with human lungs after decades
  • No well-documented multidose rat inhalation study existed; dose-response relationships had to be derived by combining single experiments

Topics

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

Medical terms in this study, explained in our Lexicon: Vitreous, Deposition, biopersistence, Chrysotile, Crocidolite, Amosite, Lung Cancer, Mesothelioma.

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