Threshold levels of Carcinogenicity of Asbestos

Our plain-English summary of Threshold levels of Carcinogenicity of Asbestos, by W.E. Smith, D.D. Hubert, L. Miller, et al (1968).

The study

• Authors: W.E. Smith, D.D. Hubert, L. Miller, M.S. Badollet, J. Churg
• Published: Internationale Konferenz ueber die biologischen Wirkungen des Asbestes (1968)
• Type of article: Conference paper
• 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

This conference paper reported hamster experiments on whether smaller asbestos doses caused tumors. Groups of 50 male hamsters got one injection of soft chrysotile, harsh chrysotile or amosite into the right chest cavity and were followed up to 700 days. Among hamsters living at least 151 days, mesotheliomas developed in 8 of 44 (18%) after 25 mg soft chrysotile and in 21% after 25 mg harsh chrysotile, where tumors came earlier. After 10 mg, 9% given harsh chrysotile and 9% given amosite developed mesotheliomas. At the lowest dose (apparently 1 mg) none did, though asbestos fibers and pleural scarring remained. The authors concluded that the cancer response was dose related, with no tumors at reduced doses in groups of this size. Repeated injections into the windpipe caused lung fibrosis, emphysema and pleural plaques but few tumors. Respiratory tract tumors developed in 8 of 33 hamsters (24%) given benzo(a)pyrene alone. They developed in a printed 54% of 31 also given 12 mg chrysotile, though that count is illegible. None occurred in a group of illegible size given 12.5 mg chrysotile alone.

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 experiments: single intrapleural injections and repeated intratracheal injections of asbestos in hamsters, plus a test of asbestos combined with benzo(a)pyrene
• Who was studied: Male hamsters, 50 per dose group, injected at about 2 months of age and followed up to 700 days. The intratracheal experiments used groups of 60 hamsters. Health Research Institute, Fairleigh Dickinson University, New Jersey, USA.
• Exposure: Single right intrapleural injection of 0.5 ml suspension. Soft chrysotile was given at 25 mg. Harsh chrysotile was given at 25 mg, 10 mg and a lowest dose (apparently 1 mg). Amosite was given at 10 mg and the same lowest dose. The chrysotiles were hand-picked from Arizona dolomite-deposit ores. Separate experiments used repeated weekly intratracheal injections of chrysotile or amosite. A further experiment gave benzo(a)pyrene with or without chrysotile.
• Main results:
  • Soft chrysotile 25 mg: 8 of 44 effective hamsters (18%) developed mesotheliomas. The first was found at 372 days.
  • Harsh chrysotile 25 mg: 21% developed mesotheliomas. The first was found at 151 days, earlier than in the soft chrysotile group.
  • Harsh chrysotile: 9% developed mesotheliomas after 10 mg and none after the lowest dose.
  • Amosite: 9% developed mesotheliomas after 10 mg and none after the lowest dose.
  • At the lowest dose of chrysotile and amosite, no tumors were seen, but fibrogenic (scarring) responses still occurred. Asbestos fibers were seen in pleural adhesions in all groups.
  • Repeated intratracheal injections in hamsters produced diffuse interstitial fibrosis, emphysema and pleural plaques.
  • Intratracheal tumors were few. No lung tumors occurred in the untreated or sham groups. One bronchial papilloma occurred after 6 mg soft chrysotile. After 25 mg amosite there was one pleural mesothelioma and one pulmonary adenocarcinoma.
  • Benzo(a)pyrene alone at a reduced total cumulative dose (printed as '4,5'): 8 of 33 hamsters (24%) developed respiratory tract tumors.
  • The same benzo(a)pyrene dose plus 12 mg chrysotile: the printed figure is 54% of 31 hamsters with respiratory tract tumors. The tumor count itself is illegible in the scan.
  • 12.5 mg chrysotile alone: no respiratory tract tumors were found. The group size is illegible.
• The authors' conclusion: The authors concluded that the carcinogenic response to asbestos was dose related. They wrote that with reduced dose, tumors were not found in groups of the size tested, which they took as experimental support for industrial hygiene measures that reduce exposure.
• Limitations the authors state:
  • The absence of tumors at low doses applied only to this species and to groups of the size tested.
  • The authors indicated that intrapleural injection does not closely simulate human exposure, which is why they also used intratracheal injection.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Amosite, Mesothelioma, Fibrosis, Emphysema, Pleural Plaques.

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