The sizes, shapes, and mineralogy of asbestos structures that induce lung tumors or mesothelioma in AF/HAN rats following inhalation

Our plain-English summary of The sizes, shapes, and mineralogy of asbestos structures that induce lung tumors or mesothelioma in AF/HAN rats following inhalation, by D.W. Berman, K.S. Crump, E.J. Chatfield, et al (Risk Analysis, 1995).

The study

• Authors: D.W. Berman, K.S. Crump, E.J. Chatfield, J.M. Davis, A.D. Jones
• Journal: Risk Analysis
• Published: 1995;15(2):181-95
• Cited by: 85 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Data from inhalation studies in which AF/HAN rats were exposed to nine different types of asbestos dusts (in 13 separate experiments) are employed in a statistical analysis to determine if a measure of asbestos exposure (expressed as concentrations of structures with defined sizes, shapes and mineralogy) can be identified that satisfactorily predicts the observed lung tumor or mesothelioma incidence in the experiments. Due to limitations in the characterization of asbestos structures in the original studies, new exposure measures were developed from samples of the original dusts that were re-generated and analyzed by transmission electron microscopy using a direct transfer technique. This analysis provided detailed information on the mineralogy (i.e., chrysotile, amosite, crocidolite or tremolite), type (i.e., fiber, bundle, cluster, or matrix), size (length and width) and complexity (i.e., number of identifiable components of a cluster or matrix) of each individual structure. No univariate measure of exposure was found to provide an adequate description of the lung tumor responses observed among the inhalation studies, although the measure most highly correlated with tumor incidence is the concentration of structures > or = 20 microns in length. Multivariate measures of exposure were identified that do adequately describe the lung tumor responses. Structures contributing to lung tumor risk appear to be long (> or = 5 microns) thin (0.4 microns) fibers and bundles, with a possible contribution by long and very thick (> or = 5 microns) complex clusters and matrices. Potency appears to increase with increasing length, with structures longer than 40 microns being about 500 times more potent than structures between 5 and 40 microns in length. Structures < 5 microns in length do not appear to make any contribution to lung tumor risk. This analysis did not find a difference in the potency of chrysotile and amphibole toward the induction of lung tumors. However, mineralogy appears to be important in the induction of mesothelioma with chrysotile being less potent than amphibole.

In plain English

This statistical study re-analyzed 13 inhalation experiments by Davis and colleagues. In them, male AF/HAN rats breathed one of nine asbestos dusts (UICC crocidolite, Korean tremolite, four chrysotile and three amosite samples) for 7 hours a day, 5 days a week, on 224 days over one year. Because original fiber measurements were limited, the authors examined regenerated dusts from archived samples by transmission electron microscopy. They tested which exposure measure best predicted lung tumors, counting benign and malignant tumors together. Neither dust mass nor phase contrast microscopy fiber counts gave a consistent dose-response; no single measure fit adequately. A combined index did fit. In it, thin structures 40 micrometers or longer were about 500 times more potent than thin structures 5 to 40 micrometers long, and structures shorter than 5 micrometers were assigned zero potency. No chrysotile-amphibole difference was detected for lung tumors. Mesotheliomas were few. Assuming similar size effects for both tumor types, the results suggested amphibole was 3.4 times more potent than chrysotile for mesothelioma in rats. The authors noted uncertainty from few very long structures and from regenerated dusts.

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: Statistical re-analysis of tumor data from 13 earlier rat inhalation experiments, using new transmission electron microscopy (TEM) measurements of dusts regenerated from archived samples
• Who was studied: Groups of 40 male AF/HAN rats, aged 3 months at the start, from a series of studies by Davis et al. using a common protocol in the same laboratory. Control groups from the various studies were combined into one group.
• Exposure: Inhalation of nine asbestos dusts (UICC crocidolite, Korean tremolite, four types of chrysotile, three types of amosite) for 7 hours a day, 5 days a week, for 224 days over one year, followed by at least another year of observation. Some samples were studied at two doses or on multiple occasions.
• Main results:
  • Among groups exposed to similar dust mass concentrations, lung tumor responses ranged from 0 of 42 animals (short amosite) to 20 of 40 animals, 50 percent (long chrysotile).
  • Fiber concentration measured by phase contrast microscopy (PCM) in the original studies showed no consistent dose-response pattern for lung tumors.
  • No single (univariate) exposure measure adequately described the lung tumor data. The measure most highly correlated with tumor incidence was the concentration of structures 20 micrometers or longer.
  • The 'optimum exposure index' gave an adequate fit to the lung tumor data (goodness-of-fit p-value 0.24, 10 degrees of freedom). It assigned relative potency 0.0017 to structures thinner than 0.3 micrometers and 5 to 40 micrometers long, 0.853 to structures thinner than 0.3 micrometers and 40 micrometers or longer, and 0.145 to structures 5 micrometers or more wide and 40 micrometers or longer.
  • Structures longer than 40 micrometers appeared about 500 times more potent than structures 5 to 40 micrometers long.
  • Structures shorter than 5 micrometers were assigned zero potency. The 95 percent upper limit for their potency was no more than about 1/20 of that estimated for fibers or bundles 5 to 40 micrometers long.
  • For lung tumors, the test of a difference in potency between chrysotile and amphibole was not significant (p = 0.72).
  • For mesothelioma, the estimated probability relative to the probability of lung tumors was 0.058 for chrysotile and 0.20 for amphibole. These values were significantly different (p = 0.032).
  • The authors calculated that amphibole was 3.4 times more potent than chrysotile for causing mesothelioma in rats, assuming the relative potencies of different size categories are about the same for mesothelioma and lung tumors.
• The authors' conclusion: The authors concluded that lung tumor induction in rats after asbestos inhalation is a function of the size and shape of the structures. Long, thin fibers and bundles appear to contribute, with a possible contribution from long, very thick complex clusters and matrices. Mineralogy appears important for mesothelioma, with chrysotile less potent than the amphiboles.
• Limitations the authors state:
  • Too few mesotheliomas were observed for a full analysis, so the evaluation was limited primarily to lung tumors.
  • The database contained only a limited number of very long structures, adding uncertainty to the potency estimates for the most potent structures.
  • The statistical analysis assumed fiber concentrations were known with certainty.
  • Exposure estimates relied on regenerated dusts rather than the actual dusts the animals breathed.
  • The positive potency found for very thick structures could be an artifact of limitations in the database and the chosen size cutpoints.
  • The finding of no mineralogy difference for lung tumors may not apply to humans, because chrysotile degrades more rapidly than amphibole in the body and humans live much longer than the experimental animals.

Topics

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

Medical terms in this study, explained in our Lexicon: Mineralogy, Mesothelioma, Asbestos Exposure, Transmission Electron Microscopy (TEM), Chrysotile, Amosite, Crocidolite, Tremolite.

Related studies

• Size and shape of airborne asbestos fibres in mines and mills — C.Y. Hwang (1983)
• Experimental lung tumors following specific intrabronchial application of chrysotile asbestos. Longitudinal light and electron microscopic investigations in rats — E. Fasske (1988)
• Pulmonary and pleural leukocytes from F344 rats produce elevated levels of fibronectin following inhalation of refractory ceramic fibers — T.R. Gelzleichter, J.B. Mangum, et al. (1996)
• Inhalation studies on the effects of tremolite and brucite dust in rats — J.M. Davis, J. Addison, et al. (1985)
• Inhalation and injection studies in rats using dust samples from chrysotile asbestos prepared by a wet dispersion process — J.M. Davis, J. Addison, et al. (1986)
• Changes in numbers and dimensions of chrysotile asbestos fibers in lungs of rats following short-term exposure — V.L. Roggli, A.R. Brody (1984)

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