Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: a weight-of-the-evidence approach

Our plain-English summary of Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: a weight-of-the-evidence approach, by L.D. Maxim, E.E. McConnell (Regulatory Toxicology and Pharmacology, 2001).

The study

• Authors: L.D. Maxim, E.E. McConnell
• Journal: Regulatory Toxicology and Pharmacology
• Published: 2001;33(3):319-42
• Type of article: Review
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This analysis reviews the available literature on interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers (SVFs). This topic is of substantial practical importance because most quantitative risk analyses on the effects of inhalation of SVFs are based upon extrapolation of data from rodent inhalation studies. Available information on interspecies comparisons for both dosimetry (the relation between exposure concentration and fiber lung burden) and potency (the relation between lung burden and disease) is summarized. Dosimetry models indicate that, on a normalized basis, fiber deposition and clearance rates are lower in humans than rats. Potency is less well understood than dosimetry, in part because the source of relevant human data is asbestos studies, which are adequate to demonstrate hazard, but are problematic in other regards. There are significant interspecies differences between the mouse, hamster, rat, and human. The available evidence suggests that the rat is preferable as a model for the human. Rats develop fibrosis at comparable lung burdens [10(6) long (> 20 microm length) fibers per gram of dry lung] to those in humans. This analysis concludes that, on a weight-of-evidence basis, there is no reason to conclude that humans are more sensitive to fibers than rats with respect to the development of lung cancer.

Copyright 2001 Academic Press.

In plain English

This was a review. The authors examined published research comparing how asbestos and man-made synthetic vitreous fibers affect rodents and humans. They focused on lung scarring (fibrosis; asbestosis in asbestos-exposed people) and lung cancer, touching only briefly on mesothelioma. Based on dosimetry models, they reported that, per unit of lung weight or lung surface, synthetic fibers settle in human lungs at a lower rate than in rat lungs but are also cleared more slowly, though a whole human lung probably receives more fibers per unit time. They estimated that fibrosis appeared in rats at 1.7 million to 20 million fibers longer than 20 micrometers per gram of dry lung. For people with asbestosis, their estimate was 1.6 million to 30 million such fibers per gram of dry lung, probably understated, they said. They argued that the claim that humans are 100 to 1,000 times more sensitive than rats rests partly on a single human lung cancer estimate, although such estimates varied 670-fold. The authors concluded there seemed little reason to believe humans and rats differ greatly in sensitivity for fibrosis or lung cancer.

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 published literature using what the authors call a weight-of-the-evidence approach; no new data were collected
• Who was studied: Published animal studies (mainly rats and hamsters, also mice), laboratory cell studies, and human studies of asbestos-exposed workers, compared across species
• Exposure: Asbestos (including chrysotile, crocidolite and amosite) and synthetic vitreous fibers such as refractory ceramic fiber (RCF), rock wool and glass fibers. The endpoints studied were fibrosis and lung cancer.
• Main results:
  • According to the dosimetry models reviewed, when normalized (per unit of lung weight or surface area), both fiber deposition and clearance rates are lower in humans than in rats.
  • Because humans breathe more air per minute, at a given airborne fiber concentration a human lung would probably receive a greater total number of fibers per unit time than a rodent lung.
  • The authors estimated that the burden of long fibers (over 20 micrometers) associated with fibrosis in rats ranged from 1.7 million to 20 million fibers per gram of dry lung.
  • The authors estimated that the burden of fibers longer than 20 micrometers in humans with asbestosis ranged from 1.6 million to 30 million fibers per gram of dry lung, and said these estimates were probably understated.
  • The authors concluded that humans and rats develop fibrosis at comparable normalized fiber burdens.
  • From the cell studies reviewed, the authors judged that human and rodent cells appear to be of comparable sensitivity to fibers on basic biological measures.
  • Among published estimates of the lung cancer increase per unit of asbestos exposure in human studies, the highest estimate was 670 times the lowest. The authors argued that basing a human-versus-rat comparison on a single estimate could be misleading.
  • In the Rowe and Springer (1986) analysis that the authors reviewed, the estimates were for human lung cancer risk from 45 years of exposure at 0.5 f/cc. The geometric mean was 0.0146 for estimates from the human studies and 0.0179 (without surface area correction) or 0.0122 (with correction) for estimates from rat data.
  • The authors judged that the evidence favors the rat over other rodents as a model for humans, at least for lung cancer.
• The authors' conclusion: The authors concluded that, on a weight-of-evidence basis, there seemed little reason to believe humans and rats have greatly different sensitivities for developing pulmonary fibrosis or lung cancer.
• Limitations the authors state:
  • Exact human-rat comparisons are difficult because many asbestos studies do not report the length and diameter of the fibers in the lung.
  • Human lung burdens are mostly measured at autopsy, after fibers have been cleared, so they likely understate the burden that caused fibrosis.
  • Mesothelioma was only briefly addressed.
  • Models of how asbestos is deposited in and cleared from the lung are less developed than those for synthetic fibers.
  • Because humans live longer than rats, the effects of fiber clearance may not be properly reflected in rat experiments.

Topics

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

Medical terms in this study, explained in our Lexicon: Vitreous, Deposition, Fibrosis, Fibers Per Gram, Lung Cancer.

Related studies

• Differential in vitro cellular response induced by exposure to synthetic vitreous fibers (SVFs) and asbestos crocidolite fibers — G. Cardinali, D. Kovacs, et al. (2006)
• Free radical activity of synthetic vitreous fibers: iron chelation inhibits hydroxyl radical generation by refractory ceramic fiber — D.M. Brown, C. Fisher, et al. (1998)
• Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers — H. Greim, M.J. Utell, et al. (2014)
• Synthetic vitreous fibers: a review of toxicology research and its impact on hazard classification — T.W. Hesterberg, G.A. Hart (2001)
• Occupational exposure to asbestos and man-made vitreous fibers, and risk of lung cancer: evidence from two case-control studies in Montreal, Canada — J. Pintos, M.E. Parent, et al. (2008)
• Risk of mesothelioma and occupational exposure to asbestos and man-made vitreous fibers: evidence from two case-control studies in Montreal, Canada — J. Pintos, M.E. Parent, et al. (2009)

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