Asbestos-Induced Intrathoracic Tissue Reactions

Our plain-English summary of Asbestos-Induced Intrathoracic Tissue Reactions, by P. Gross, R.A. Harley JR (1973).

The study

• Authors: P. Gross, R.A. Harley JR
• Published: Archives of Pathology. October 1973, Volume 96 Copyright 1973, American Medical Association
• Type of article: Journal article
• Our copy: from Johns-Manville's own medical library. The article is still under copyright, so we describe it here rather than post it.

In plain English

In this animal experiment, the authors injected asbestos into the right chest cavity of rats and hamsters. Canadian chrysotile, amosite and crocidolite were each prepared five ways: hammer-milled to coat the fibers with nickel-containing metal, chemically treated to remove trace metals, hand-picked to avoid any metal contact ("metal-free"), heated to 900 to 1,000 C, or treated and then heated. In total, 430 rats and 239 hamsters were injected. Counting only animals that lived at least as long as the earliest tumor appeared, malignant tumors occurred in 35 of 192 rats (18%) and 15 of 150 hamsters (10%). Animals given heated asbestos had a tumor rate of about 2%. With unheated asbestos the rate was about ten times higher: 33% in rats and 21% in hamsters. Adding or removing trace metals made no significant difference, so the authors abandoned the idea that trace metals cause asbestos cancer. Chrysotile produced the fewest tumors. The authors classified 25 of the 35 rat tumors as fibrosarcomas and four as mesotheliomas, noting that some fibrosarcomas might have been mesotheliomas. The authors concluded that not all chest-wall tumors are mesotheliomas.

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: intrathoracic (intrapleural) injection of differently modified asbestos dusts into rats and hamsters, with the animals allowed to live out their lives.
• Who was studied: Male rats weighing 150 to 200 gm, 430 injected (116 with amosite, 176 with crocidolite, 139 with chrysotile, as printed). Also 239 hamsters, of which only 157 survived 7½ months or longer. Done at the Industrial Health Foundation, Pittsburgh, and the Medical University of South Carolina; published 1973.
• Exposure: Canadian chrysotile, amosite and crocidolite, each prepared five ways. (1) Hammer-milled for 12 hours to add nickel and other metals from the mill. (2) Ball-milled and heated at 900 C (chrysotile), 950 C (crocidolite) or 1,000 C (amosite). (3) Treated with aqua regia and edetic acid to remove trace metals. (4) Treated and then heated. (5) Hand-picked "metal-free" fibers milled in plastic. Each rat received a 1-ml injection of a 50 mg/ml suspension (50 mg). Hamsters received a smaller amount in 0.5 ml.
• Main results:
  • Overall tumor counts by fiber. In rats: amosite 12/63 (19%), crocidolite 15/75 (20%), chrysotile 8/54 (15%), total 35/192 (18%). In hamsters: amosite 12/68 (18%), crocidolite 3/54 (6%), chrysotile 0/28 (0%), total 15/150 (10%).
  • Animals injected with heated asbestos (whether or not also chemically treated) had a tumor incidence of around 2%. The combined unheated groups had about ten times that: 21% in hamsters and 33% in rats.
  • There was no significant difference in tumor incidence among the unheated forms of asbestos. This held whether trace metals had been added by hammer-milling, removed chemically, or neither.
  • Of the 35 malignant rat tumors, 25 were classified as fibrosarcomas, four as mesotheliomas, three as rhabdomyosarcomas, two as osteogenic sarcomas (fibrosarcomas with bone formation), and one as a fibroliposarcoma.
  • The rat tumors were, with few exceptions, well differentiated. The hamster tumors were undifferentiated sarcomas.
  • Chrysotile was associated with the lowest tumor incidence in both species. Amosite and crocidolite gave about the same incidence in rats, but amosite gave a higher incidence than crocidolite in hamsters.
  • The earliest tumor appeared in a rat that survived 13 months and in a hamster that survived 7½ months. Only animals surviving at least that long were counted in the tumor incidence.
  • Animals given heated, or treated and heated, asbestos generally showed less severe and less extensive inflammation than the other groups.
  • Obvious involvement of the visceral pleura (lung surface) was infrequent compared with the parietal pleura (chest wall).
• The authors' conclusion: The authors concluded that tissues other than mesothelium may also develop malignant tumors after intrapleural asbestos injection, and that not all tumors arising from the chest wall are mesotheliomas. They also concluded that the trace-metal hypothesis must be abandoned and that prolonged heating diminished the pathogenic potential of the three asbestos types.
• Limitations the authors state:
  • The tumors diagnosed as fibrosarcoma may include a few mesotheliomas. The authors could not tell a well-differentiated fibrous mesothelioma from a well-differentiated fibrosarcoma without tissue suitable for electron microscopy or tissue culture.
  • Deaths were not necessarily caused by the asbestos injections, because two separate epidemics of pneumonia occurred among the rats.
  • There was considerable early mortality at the dose used in several groups, so extra rats had to be injected.

Topics

Medical terms in this study, explained in our Lexicon: Intrathoracic, Chrysotile, Amosite, Crocidolite, Mesothelioma.

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