Challenges in defining thresholds for health effects: some considerations for asbestos and silica

Our plain-English summary of Challenges in defining thresholds for health effects: some considerations for asbestos and silica, by J.E. Goodman, L.R. Rhomberg, S.M. Cohen, et al (Frontiers in Epidemiology, 2025).

The study

• Authors: J.E. Goodman, L.R. Rhomberg, S.M. Cohen, K.A. Mundt, B. Case, I. Burstyn, M.J. Becich, G. Gibbs
• Journal: Frontiers in Epidemiology
• Published: 2025;5:1557023
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This paper summarizes several presentations in the Thresholds in Epidemiology and Risk Assessment session at the Monticello III conference. These presentations described evidence regarding thresholds for particles, including asbestos and silica, and cancer (e.g., mesothelioma) and noncancer (e.g., silicosis) endpoints. In the case of exposure to various types of particles and malignancy, it is clear that even though a linear non-threshold model has often been assumed, experimental and theoretical support for thresholds exist (e.g., through particle clearance, repair mechanisms, and various other aspects of the carcinogenic process). For mesothelioma and exposure to elongate mineral particles (EMPs), there remains controversy concerning the epidemiological demonstration of thresholds. However, using data from the Québec mining cohort studies, it was shown that a "practical" threshold exists for chrysotile exposure and mesothelioma. It was also noted that, in such evaluations, measurement error in diagnosis and exposure assessment needs to be incorporated into risk analyses. Researchers were also encouraged to use biobanks that collect specimens and data on mesothelioma to more precisely define cases of mesothelioma and possible variants for cases of all ages, and trends that may help define background rates and distinguish those mesotheliomas related to EMP exposures from those that are not, as well as other factors that support or define thresholds. New statistical approaches have been developed for identifying and quantifying exposure thresholds, an example of which is described for respirable crystalline silica (RCS) exposure and silicosis risk. Finally, the application of Artificial Intelligence (AI) to considering the multiple factors influencing risk and thresholds may prove useful.

© 2025 Goodman, Rhomberg, Cohen, Mundt, Case, Burstyn, Becich and Gibbs.

In plain English

This article is a conceptual analysis, not a new study. It summarized presentations from a session on exposure thresholds at the Monticello III conference, covering asbestos and mesothelioma, and respirable crystalline silica and silicosis. It reported exploratory analyses of Québec miners and millers exposed principally to chrysotile. After low-confidence diagnoses and short-duration cases were removed, 23 mesothelioma cases remained. Their mean estimated cumulative exposure was over 1,000 fiber/cc-years, and the lowest was 135.7 f/cc-years. The authors said these estimates were exploratory, applied to a selective subsample of cases, and point to a threshold of 100 f/cc-years or greater. The article also described modelling work. In one Monte Carlo simulation, 72% of fitted models showed thresholds for chrysotile cohorts. It also described a segmented Cox regression method for silica but gave no silica threshold value. The authors concluded that the evidence indicates there are situations in which thresholds for asbestos and silica exist. They noted many sources of uncertainty, including the mesothelioma diagnosis and exposure assessment, and said that small numbers of mesothelioma deaths severely limit statistical modelling.

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: Conceptual analysis summarizing presentations at a conference session (not an original study); includes exploratory re-analysis of existing Québec cohort data and descriptions of modelling work, some of it in submitted manuscripts
• Who was studied: Presentations from the Thresholds in Epidemiology and Risk Assessment session at the Monticello III conference. The main data discussed were from Québec chrysotile miners, millers and factory workers, their families and neighbors, and from the German Porcelain Workers Study (silica).
• Exposure: Asbestos and other elongate mineral particles. The main focus was chrysotile, with tremolite in some Québec mines and crocidolite and/or amosite at a factory. Respirable crystalline silica was also discussed.
• Main results:
  • In exploratory Québec analyses of 23 mesothelioma cases (after removing low-confidence diagnoses and short-duration cases), the cases had a mean estimated exposure of over 1,000 f/cc-years, compared with a cohort average of approximately 500 f/cc-years. The lowest case had an estimated exposure of 135.7 f/cc-years.
  • Among the 17 of 23 cases with chrysotile lung content available, a central tendency of cumulative chrysotile exposure of 148.8 f/cc-years was reported. The authors said a confidence interval is difficult to establish.
  • The authors stated that these exploratory estimates point to a threshold value of 100 f/cc-years or greater.
  • Describing an earlier study by Case et al. of ten women with mesothelioma near Thetford Mines, the article reported reconstructed exposures averaging 226.1 f/cc-years (range 84.5 to 525.6 f/cc-years).
  • In a Monte Carlo simulation on chrysotile cohort data (described in more depth in a submitted paper), 72% of fitted models confirmed thresholds. The average threshold was 25.6 f/cc-years (95% CI: 24.2 to 27.1).
  • A filter model applied to non-textile chrysotile cohorts supported a threshold model, with a threshold level of 162 f/cc-years.
  • For silica and silicosis in the German porcelain workers data, the article described a segmented Cox regression method for estimating a threshold. It did not report a threshold value.
  • The authors stated that environmental exposure studies (for example Kubota in Japan, Casale Monferrato in Italy, and Wittenoom in Western Australia) did not provide confident measures of actual exposure levels.
• The authors' conclusion: The authors concluded that the evidence indicates there are situations in which thresholds for asbestos and silica exist. They said methods to establish thresholds quantitatively should be better developed, and urged researchers to include the possibility of a threshold in their analyses.
• Limitations the authors state:
  • There are many sources of uncertainty, including the mesothelioma diagnosis itself and exposure assessment.
  • The Québec exposure estimates apply to a selective subsample of cases and are exploratory.
  • Mesothelioma diagnoses were of low confidence in five Québec cases and of moderate confidence in 14.
  • The relatively small numbers of mesothelioma deaths, with fewer expected over time, severely limit statistical modelling.

Topics

Medical terms in this study, explained in our Lexicon: Epidemiology, Mesothelioma, Silicosis, Carcinogenic, elongate mineral particles (EMPs), Chrysotile, Background Rate, Crystalline.

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