Comparison of various methodological approaches to model asbestos thresholds for mesothelioma

Our plain-English summary of Comparison of various methodological approaches to model asbestos thresholds for mesothelioma, by J.E. Goodman, A. Korchevskiy, A.G. Wylie (Frontiers in Public Health, 2025).

The study

• Authors: J.E. Goodman, A. Korchevskiy, A.G. Wylie
• Journal: Frontiers in Public Health
• Published: 2025;13:1569343
• Type of article: Review
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: There is evidence to support several modes of action (MoAs), and particularly non-genotoxic MoAs, for mesothelioma induced by asbestiform elongate mineral particles (EMPs). In turn, these MoAs provide biological support for dose-response relationships that are non-linear and that include a threshold. However, statistical models of human data have not adequately addressed threshold dose-response relationships for asbestiform EMPs and mesothelioma. In addition, unlike other carcinogens, asbestiform EMPs are not uniform materials and display a range of properties.

Objectives: Our objective was to review various approaches for applying threshold dose-response models to asbestiform EMPs and mesothelioma.

Materials And Methods: We collected data from several sources, including the Surveillance, Epidemiology, and End Results (SEER) Program and published case-control studies, cohort studies, and a meta-analysis that evaluated various mineral types of asbestos and mesothelioma risk. Several threshold-based models were fit to the available data. We also evaluated thresholds for certain fiber characteristics.

Results: Certain characteristics of asbestiform EMPs, such as width, length, and surface area, likely have thresholds for mesothelioma. Theoretical models and models based on epidemiology data supported thresholds. A Monte Carlo evaluation of the threshold hypothesis for mesothelioma in a meta-analysis of occupational exposures to various mineral fiber types, using a cumulative exposure metric, demonstrated the likelihood of a threshold to be 72% for non-textile chrysotile, 80.9% for textile chrysotile, 84% for amosite, and 60% for crocidolite. A multi-stage clonal expansion (MSCE) model applied to the SEER mesothelioma registry data demonstrated a good fit with the inclusion of a threshold by a surrogate predictor of cumulative exposure to amphiboles. Finally, lung burden studies also support a threshold. Our preliminary estimate of a central-tendency cumulative exposure threshold level for non-textile chrysotile is ~90 f/cc-years. Based on our proposed approach, we suggest thresholds of 1.04 f/cc-years for amosite, 0.25 f/cc-years for crocidolite, and 4.3-10.9 f/cc-years for tremolite. Future studies should be conducted to support these estimates.

Conclusions: While uncertainties remain, many angles of scientific evidence support the existence of mineral-specific thresholds for mesothelioma.

Copyright © 2025 Goodman, Korchevskiy and Wylie.

In plain English

The authors used mathematical models to test whether there is an exposure level, or threshold, below which asbestos does not raise mesothelioma risk. The main analyses used published data on six non-textile chrysotile cohorts from mining and general industry, including Québec and Russian miners and millers and asbestos cement and friction products workers. In a Monte Carlo simulation, 72% of fitted models supported a threshold, with an average of 25.6 f/cc-years (fiber-per-cubic-centimeter-years; 95% CI 24.2–27.1). A model based on exposure intensity and duration gave about 2 f/cc, which the authors equated to 90 f/cc-years over 45 years. A "filter model" gave 162 f/cc-years. The authors took about 90 f/cc-years as a possible threshold for non-textile chrysotile. By scaling with published potency ratios, they suggested 1.04 f/cc-years for amosite, 0.25 for crocidolite and 4.3 for Libby amphibole asbestos. A separate filter-model calculation from one Libby datapoint gave 10.88. The authors concluded that, while uncertainties remain, many angles of evidence support a threshold. They noted that all estimates are model-based, that the models used non-textile chrysotile cohorts only, and that the amphibole estimates rest on potency ratios.

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: Statistical modeling analysis of published cohort data (labeled original research), testing several threshold dose-response models, with discussion of fiber characteristics and lung burden studies
• Who was studied: Six mining and general industry chrysotile cohorts: Québec miners and millers, Balangero miners and millers, Quinghai miners, New Orleans asbestos cement workers, Connecticut asbestos friction products workers, and Russian miners and millers. Five were taken from Darnton's recent analysis and the sixth from Schüz et al. Textile cohorts were excluded.
• Exposure: Cumulative exposure (PCM f/cc-years) and exposure intensity to non-textile chrysotile. Thresholds were then extrapolated to amosite, crocidolite and Libby amphibole asbestos (LAA, used as a surrogate for tremolite) based on potency.
• Main results:
  • Monte Carlo simulation of non-textile chrysotile cohorts: 72% of models supported thresholds.
  • Average threshold in the simulation for non-textile chrysotile: 25.6 f/cc-years (95% CI 24.2–27.1), with 5th and 95th percentiles of 3.3 and 52.9 f/cc-years.
  • Intensity and duration model for chrysotile cohorts: an exposure intensity threshold of about 2 f/cc, corresponding to 90 f/cc-years assuming a maximum exposure duration of 45 years.
  • Filter model for non-textile chrysotile: threshold of 162 f/cc-years.
  • The authors took an average of about 90 f/cc-years as a possible threshold for non-textile chrysotile.
  • Thresholds scaled by potency ratios: 4.3 f/cc-years for LAA, 1.04 f/cc-years for amosite, and 0.25 f/cc-years for crocidolite.
  • A separate filter-model calculation using the single LAA datapoint and assumed parameter ranges gave an average threshold of 10.88 f/cc-years, standard deviation 2.8.
  • Drawing on two earlier lung burden studies (Gilham et al. and Rödelsperger et al.), the authors proposed 0.1 million amphibole fibers longer than 5 µm per dry gram of lung tissue as a possible threshold for mesothelioma.
• The authors' conclusion: The authors concluded that, while uncertainties remain, many angles of scientific evidence support a threshold for mesothelioma. Their preliminary central-tendency estimate for non-textile chrysotile was about 90 f/cc-years, with suggested thresholds of 1.04 f/cc-years for amosite, 0.25 f/cc-years for crocidolite and 4.3 to 10.9 f/cc-years for tremolite. They said future studies are needed to support these estimates.
• Limitations the authors state:
  • All threshold estimates are model-based.
  • The models were tested only on non-textile chrysotile cohorts.
  • The amphibole thresholds were derived from ratios of chrysotile to amphibole potency factors.
  • Few datapoints were available for amphiboles: three for crocidolite, three for amosite, and one for LAA.
  • Some argue that a threshold cannot be established scientifically from data alone.
  • The chrysotile thresholds should not be applied to textile cohorts without correction factors.

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, Asbestiform, elongate mineral particles (EMPs), Dose-response relationship, Epidemiology, SEER, Meta-Analysis, Occupational Exposure.

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