Asbestos-related mesothelioma: evidence for a threshold in animals and humans

Our plain-English summary of Asbestos-related mesothelioma: evidence for a threshold in animals and humans, by E.B. Ilgren, K. Browne (Regulatory Toxicology and Pharmacology, 1991).

The study

• Authors: E.B. Ilgren, K. Browne
• Journal: Regulatory Toxicology and Pharmacology
• Published: 1991;13(2):116-32
• Type of article: Review
• Cited by: 24 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. 004465).

Abstract

A threshold for mesothelioma for the major asbestos fiber types becomes not only plausible but also very likely in view of the existence of a distinct background incidence of spontaneously occurring and non-asbestos-related mesotheliomas; the high occupational doses associated with the appearance of mesotheliomas in humans; and the large number of "tumorigenic" fibers required to produce significant numbers of mesotheliomas in animals. Even when the duration of exposure associated with the appearance of mesotheliomas in humans has been brief, the exposure itself has been intense. The review of the relevant animal and human literature cited herein supports the concept of mesothelioma threshold.

In plain English

This article was a review. The authors reviewed occupational reports and animal experiments on whether a dose of asbestos exists below which mesothelioma does not ordinarily develop (a "threshold"). For humans, they listed the shortest exposures linked to mesothelioma. They judged that where exposure was intense, the duration could perhaps be as little as 2 or 3 weeks, with a cumulative dose of about 5 f/ml years. From animal experiments with amosite, chrysotile and crocidolite, judged against background tumor rates, they proposed inhalation "no-effect" levels of 2000 fiber-years for amosite, 2340 for chrysotile and 912 for crocidolite. The authors concluded that the literature strongly suggested a threshold, possibly three or more orders of magnitude above typical exposures in buildings containing asbestos. They acknowledged two objections: short-exposure cases might not yet have appeared, and brief employees are the most likely to be lost to follow-up. They replied that so many short-term employees were involved that it was unlikely none would have been identified if mathematical models were correct. They did not separately address loss to follow-up. They noted that such epidemiological evidence can never establish a negative result.

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: Review of previously published human (occupational) and animal experimental literature
• Who was studied: Published occupational series of workers with mesothelioma, giving the shortest exposure durations (Table 1). Animal experiments in rats, monkeys, mice and hamsters, selected from a compilation of the world's experimental literature on mesotheliomas.
• Exposure: Amosite, chrysotile and crocidolite asbestos, given by inhalation, intrapleural or intraperitoneal injection, or intrapleural implantation. For comparison, the review also covered non-asbestos agents: erionite, aluminum oxide fibers and ethylene oxide. The human data covered occupational exposures by fiber type.
• Main results:
  • Human data: the authors judged that, where exposure was intense, the duration associated with mesothelioma could perhaps be as little as 2 or 3 weeks, with a cumulative dose of about 5 f/ml years.
  • A gas-mask worker (reported by Jones, 1987) had a recorded history of only 2 weeks of exposure but a lung fiber count above 6 million fibers per gram of dried lung. The authors took this to mean the exposure, if really that brief, must have been very intense.
  • In the Wittenoom crocidolite miners' cohort reported by Armstrong et al. (1988), 19% worked there for less than 1 month. No mesothelioma case had been identified among those with less than 3 months of exposure.
  • Animal data: the authors proposed an inhalation "no-effect" level of 2000 fiber-years for amosite.
  • Animal data: the proposed inhalation "no-effect" level for chrysotile was 2340 fiber-years.
  • Animal data: the proposed inhalation "no-effect" level for crocidolite was 912 fiber-years.
  • In judging animal results against background, the authors treated a single mesothelioma in an individual inhalation study as compatible with background.
  • The authors stated that there are no convincing human data that chrysotile alone can produce mesotheliomas in humans.
• The authors' conclusion: The authors concluded that the data were consistent with a threshold for mesothelioma. They suggested the threshold may be three or more orders of magnitude higher than typical environmental exposures in buildings containing asbestos materials.
• Limitations the authors state:
  • Because shorter exposures would carry a lower incidence, too few people with short exposures may have been followed for cases to appear. The authors replied that, given the large number of short-term employees, it was unlikely none would have been identified if cases occurred as often as mathematical models suggested.
  • Employees with very brief exposures are the most likely to be lost to follow-up. The authors did not give a separate answer to this point.
  • Epidemiological evidence of the kind discussed cannot establish a negative result.
  • Animal-to-human comparisons are limited for chrysotile claims based on animal injection studies.

Topics

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

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

Related studies

• Background incidence of mesothelioma: animal and human evidence — E.B. Ilgren, J.C. Wagner (1991)
• Effect of NSAIDS and COX-2 inhibitors on the incidence and severity of asbestos-induced malignant mesothelioma: evidence from an animal model and a human cohort — C. Robinson, H. Alfonso, et al. (2014)
• Evidence for an amphibole asbestos threshold exposure for asbestosis assessed by autopsy in South African asbestos miners — G.K. Sluis-Cremer, E. Hnizdo, et al. (1990)
• A threshold for asbestos related lung cancer — K. Browne (1986)
• The epidemiologic evidence for elongate mineral particle (EMP)-related human cancer risk — P. Boffetta, K.A. Mundt, et al. (2018)
• The use of wild animal models to detect evidence of environmental contamination by asbestos-like substance — R. Puleio, M.R. Schiavo, et al. (2013)

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