Carcinogenicity of fibrous glass: pleural response in the rat in relation to fiber dimension

Our plain-English summary of Carcinogenicity of fibrous glass: pleural response in the rat in relation to fiber dimension, by M.F. Stanton, M. Laynard, A. Tegeris, et al (Journal of the National Cancer Institute, 1977).

The study

• Authors: M.F. Stanton, M. Laynard, A. Tegeris, E. Miller, M. May, E. Kent
• Journal: Journal of the National Cancer Institute
• Published: 1977;58(3):587-603
• Cited by: 372 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 005489).

Abstract

Seventeen fibrous glasses of diverse type or dimensional distribution induced different incidences of malignant mesenchymal neoplasms when implanted in the pleurae of female Osborne-Mendel rats for periods of more than 1 year. Neoplastic response correlated well with the dimensional distribution of fibers. Fibers less than or equal to 1.5 mu in diameter and greater than 8 mu in length yielded the highest probability of pleural sarcomas, and probability trends suggested that pleural sarcoma incidence increased with increasing lengths of fibers with diameters of less than 1.5 mu, Morphologic observations indicated that fibers less than or equal to 8 mu in length were inactivated by phagocytosis. In fibers greater than 8 mu in length, the correlation of carcinogenicity witth increasing length was difficult to explain. Since neoplastic response to a variety of types of durable fibers, particularly asbestos fibers, was similar, our experiments reinforce the idea that the carcinogenicity of fibers depends on dimension and durability rather than physicochemical properties and emphasize that all respirable fibers be viewed with caution.

In plain English

National Cancer Institute researchers tested 17 fibrous glass samples of differing type and fiber size in female Osborne-Mendel rats. A coarse glass pad carrying 40 mg of test fibers was surgically placed on the pleura (lung lining). Each test group had 30 long-term survivors; 130 pad-only rats were treated controls. Survivors were killed in the 25th month. Estimated pleural sarcoma probability ranged from 85.3% to zero; 89 pleural sarcomas were seen. The strongest correlation (0.93) linked the logit (a statistical rescaling) of tumor probability with the logarithm of fibers per microgram 0.25 micrometers or less wide and over 8 micrometers long. For fibers over 0.25 to 1.5 micrometers wide and over 64 micrometers long, it was 0.92. The authors could not tell which group mattered more. Scavenger cells seemed to engulf virtually all fibers up to 8 micrometers long but coped inadequately with fine, long ones. The authors wrote that their regression analyses suggested glass fibers under 1.5 micrometers wide and over 8 micrometers long were highly carcinogenic in rat pleura, while cautioning against rigid interpretation. They noted implantation bypasses natural routes like breathing.

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 experiment (surgical implantation of fibrous glass on the pleura of rats)
• Who was studied: Female, specific-pathogen-free Osborne-Mendel rats from the NIH colony, treated at 12 to 20 weeks of age. There were 17 experiments: each test group had 30 long-term surviving rats, and the treated-control group (experiment 17) had 130 rats.
• Exposure: A standard dose of 40 mg of test fibers in gelatin, coated onto a pad of coarse insulation-type fibrous glass. The 17 samples were mainly borosilicate fibrous glasses of different diameters and lengths, some contaminated with metals from milling. They also included a silica-slag-derived mineral wool, a filtration glass, and coarse insulation glass. Controls received the coarse glass pad vehicle only.
• Main results:
  • Across the 17 experiments, the estimated probability of pleural sarcoma ranged from 85.3% to zero.
  • In total, 89 pleural sarcomas were observed over the 17 experiments.
  • The experiments fell into high-risk (experiments 1-5), intermediate-risk (6-8) and low-risk (9-16) groups. The low-risk group differed significantly from the intermediate-risk group (P less than 0.01), which in turn differed significantly from the high-risk group (P less than 0.0001).
  • The low-risk group was not significantly different from the treated controls at the 5% level (P = 0.1).
  • The logit of estimated tumor probability was correlated with the logarithm of the number of fibers per microgram that were 0.25 micrometers or less in diameter and longer than 8 micrometers. The correlation coefficient was 0.93, the highest in the authors' table of coefficients.
  • The logit of estimated tumor probability was also correlated with the logarithm of the number of fibers per microgram that were between 0.25 and 1.5 micrometers in diameter and longer than 64 micrometers. The correlation coefficient was 0.92.
  • These two fiber-count measures were themselves correlated at 0.95, so the authors could not determine which fiber group was more important for carcinogenesis.
  • The authors observed that scavenger cells (phagocytes) efficiently entrapped virtually all fibers 8 micrometers or less in length.
  • Phagocytosis seemed inadequate to handle fine, long fibers. In these lesions, collagen accumulated, and fine, long fibers lay in a collagenous matrix, seemingly free of contact with phagocytes.
  • By rough comparison, the degree of fibrosis matched the probability of pleural sarcomas.
• The authors' conclusion: The authors wrote that, taken together, the regression analyses would suggest that glass fibers with diameters less than 1.5 micrometers and lengths greater than 8 micrometers were highly carcinogenic in the rat pleura, and that fibers larger or smaller than these dimensions were less carcinogenic. They also cautioned that the equations could not be interpreted too rigidly.
• Limitations the authors state:
  • The authors said the regression equations could not be interpreted too rigidly for three reasons: the estimated particle size distributions were subject to considerable sampling error, the range of fiber dimensions tested was limited, and the choice of size ranges was arbitrary.
  • The implantation method bypasses natural exposure routes such as inhalation, so the authors said it is inappropriate for evaluating many aspects of environmental hazard.
  • The 130 treated controls were too few to rule out that single tumors in the low-risk experiments were due to the coarse glass vehicle or to nonspecific injury to the pleura.
  • The authors could not explain why experiment 7 did not yield a higher probability of pleural sarcomas.

Topics

Medical terms in this study, explained in our Lexicon: Fiber Dimensions, Neoplasm, Sarcoma, Phagocytosis, Respirable Fiber.

Related studies

• Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length — G. Forget, M.J. Lacroix, et al. (1986)
• Pulmonary response of hamsters to fibrous glass: chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene — V.J. Feron, P.M. Scherrenberg, et al. (1985)
• Tumorigenicity of cellulose fibers injected into the rat peritoneal cavity — R.T. Cullen, B.G. Miller, et al. (2002)
• Are glass fibres carcinogenic to man? A critical appraisal — J. Milne (1976)
• Fibrous glass and cancer — P.F. Infante, L.D. Schuman, et al. (1994)
• Tumors of the pleura induced with asbestos and fibrous glass — P. Gross (1973)

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