Detection of mineral fibre carcinogenicity with the intraperitoneal test--recent results and their validity

Our plain-English summary of Detection of mineral fibre carcinogenicity with the intraperitoneal test--recent results and their validity, by F. Pott (The Annals of Occupational Hygiene, 1995).

The study

• Author: F. Pott
• Journal: The Annals of Occupational Hygiene
• Published: 1995;39(5):771-9
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The general experimental design of intraperitoneal (i.p.) carcinogenicity studies with inorganic fibres in rats is described. In a current study, in addition to glass microfibres, size-separated fine respirable fractions of commercial insulation wools (MMVF-11 and MMVF-21) also induced mesotheliomas after i.p. injection of 0.4 x 10(9) fibres. These fibre samples were also tested in inhalation studies. A special glass fibre type (B-01), which is of interest because of its low biodurability, induced tumours with 25- and 50-fold higher doses. The i.p. model has been proved to be much more specific and sensitive for testing the carcinogenicity of inorganic fibres than the inhalation model. Objections to this conclusion are cited and discussed with alternative arguments.

In plain English

This paper, from a Düsseldorf institute, did four things. It described how intraperitoneal (i.p.) tests are run, injecting fibres into rats' abdominal cavities. It gave interim results from a larger ongoing i.p. study. It answered a critic, McConnell, who rejected the method. And it answered a workshop question on whether such tests can be validated for human hazard assessment. The general protocol, used for most current study groups, called for mostly female Wistar rats, at least 32 per group, observed for 30 months. Fine, size-separated fractions of a glass wool (MMVF-11) and a rock wool (MMVF-21) induced mesotheliomas, at a dose the abstract gives as 0.4 x 10^9 fibres. A low-biodurability glass fibre, B-01, negative at 5 x 10^9 fibres in earlier work, produced similar tumour rates at 10 x 10^9 and 20 x 10^9 fibres, doses over an order of magnitude higher. A preliminary ranking of fibre samples by estimated potency per fibre included actinolite, crocidolite, chrysotile and tremolite. The results were interim, and 'positive' rats included probable mesotheliomas judged by eye. The author concluded the answer was yes.

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: Methods description and commentary, with interim results from an ongoing animal experiment (intraperitoneal injection of fibres in rats) and a point-by-point reply to criticism of the method
• Who was studied: Under the general protocol used for most of the current study groups: Wistar rats, mostly female, aged 8 to 10 weeks, at least 32 per group, observed for 30 months after injection
• Exposure: Intraperitoneal injection of glass microfibres and of size-separated fine respirable fractions of commercial insulation wools: Certain Teed B glass wool (MMVF-11) and rock wool (MMVF-21). Also a low-biodurability glass fibre (B-01) given at 10 x 10^9 and 20 x 10^9 fibres in 20 or 40 injections.
• Main results:
  • In the current study, the fine fractions of MMVF-11 and MMVF-21 induced mesotheliomas after i.p. injection. The scanned text garbles the exponent of the dose; the PubMed abstract gives it as 0.4 x 10^9 fibres.
  • Glass fibre B-01 had given negative results in earlier work at 5 x 10^9 fibres. At 10 x 10^9 and 20 x 10^9 fibres it induced tumour rates similar to those of the commercial glass and stone wool fractions, but at doses more than one order of magnitude higher.
  • The author presented an estimated ranking of fibrous dust samples by carcinogenic potency per fibre. It was based on i.p. studies and biodurability findings and included actinolite, crocidolite, chrysotile UICC-B, tremolite and man-made fibres.
  • Replying to the criticism, the author cited an earlier study (Pott et al., 1989) of three doses of actinolite. In that study the time until tumours appeared lengthened as the dose decreased. Average survival of tumour-bearing rats was 116 weeks at the lowest dose (8 rats, 23%), 99 weeks at the middle dose and 86 weeks at the highest dose.
• The authors' conclusion: The author concluded that intraserosal injection tests can be validated to play a role in hazard assessment for humans. The author's view was that the i.p. test is more sensitive than other exposure routes and is specific for mineral fibres, without the confounding by non-fibrous particles seen in the lung.
• Limitations the authors state:
  • The results were interim. Rats counted as 'positive' included animals with probable mesotheliomas judged from what was visible to the eye, not only those confirmed under the microscope.
  • For B-01, the author could not be certain whether the maximum tolerated dose had been reached.
  • The author stated that the criticism could not be analysed extensively in this paper because of limited space.
  • In one earlier series of i.p. experiments, an infectious disease was a large problem.

Topics

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

Medical terms in this study, explained in our Lexicon: Respirable Fraction, Mesothelioma.

Related studies

• Results of current intraperitoneal carcinogenicity studies with mineral and vitreous fibres — M. Roller, F. Pott, et al. (1996)
• A comparison of the results from intra-pleural and intra-peritoneal studies with those from inhalation and intratracheal tests for the assessment of pulmonary responses to inhalable dusts and fibres — G. Drummond, R. Bevan, et al. (2016)
• A review of carcinogenicity studies of asbestos and non-asbestos tremolite and other amphiboles — J. Addison, E.E. McConnell (2008)
• A trial on the quantitative risk assessment of man-made mineral fibers by the rat intraperitoneal administration assay using the JFM standard fibrous samples — S. Adachi, K. Kawamura, et al. (2001)
• Testing of fibrous particles: short-term assays and strategies — D. Bernstein, V. Castranova, et al. (2005)
• Mesothelioma dose response following intraperitoneal injection of mineral fibres — J.M. Davis, R.E. Bolton, et al. (1991)

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