Asbestos lung cancer risks: comparison of animal and human extrapolations

Our plain-English summary of Asbestos lung cancer risks: comparison of animal and human extrapolations, by J.N. Rowe, J.A. Springer (Risk Analysis, 1986).

The study

• Authors: J.N. Rowe, J.A. Springer
• Journal: Risk Analysis
• Published: 1986;6(2):171-80
• Cited by: 9 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. 000430).

Abstract

Using the most comprehensive inhalation study available, (Wagner, et al., 1974), the dose-response effects of the four major types of asbestos fibers (amosite, anthophyllite, crocidolite, and chrysotile: Canadian, Rhodesian) for lung cancer have been determined. From linear regression analysis of the animal data and five human epidemiology studies giving a wide range of risk estimates, slopes of the curves have been determined and lifetime risk estimates made. Projected risks for rats are presented with and without surface area (s.a.) conversion factors. On the basis of cumulative exposure, the geometric mean of the point estimates for the human studies (0.0146) is quite close to the geometric mean of the animal data (0.0179 without s.a.; 0.0122 with s.a. calculations). These values also match quite well if one of the studies (McDonald, et al.) is eliminated (geometric mean = 0.031) due to qualitatively different exposure considerations (mining and milling vs. industrial environments). Animal risks based on a concentration per day basis (assuming an average 70-year lifespan for humans) are below the lowest human estimate but within 5-6 fold (less) of the projected risk from nonsmoking asbestos workers (2.2 X 10(-3) using the Hammond et al. study.

In plain English

The authors collected no new data; they compared a published rat inhalation experiment (Wagner et al., 1974) with five worker studies chosen to span the widest range of risk estimates. The rats breathed amosite, anthophyllite, crocidolite, Canadian chrysotile or Rhodesian chrysotile for 1 day to 24 months. Only lung carcinomas in the rats were counted. From straight-line dose-response fits, the authors projected lifetime lung cancer risk for exposure to 0.5 fibers per cubic centimeter for 45 years. Rat projections varied at most 2.4-fold across fiber groups, while the worker studies varied 236-fold. The geometric mean of the worker estimates (0.0146) was close to the rat estimates (0.0179 without, 0.0122 with a surface-area adjustment). An approximate nonsmoker adjustment of one worker study gave 2.2 times 10 to the minus 3: 6 to 8 times below rat estimates based on cumulative exposure, but above the rat daily-dose estimate (0.4 to 0.5 times 10 to the minus 3). The authors concluded that this suggests some validity in animal-to-human extrapolation for asbestos. They noted gaps in knowledge about lung dose, unit conversions and smoking.

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: Quantitative risk-assessment reanalysis of previously published data: linear regression of one rat inhalation experiment compared with five published human epidemiology studies
• Who was studied: Animal data: SPF Wistar rats from the Wagner et al. (1974) inhalation study (859 exposed, 154 controls). Human data: five published worker studies, by Hammond et al., Henderson and Enterline, Dement et al., Seidman et al., and McDonald et al. The McDonald et al. study was of chrysotile mining and milling.
• Exposure: Rats inhaled UICC standard reference samples of amosite, anthophyllite, crocidolite, Canadian chrysotile and Rhodesian chrysotile at 9.7 to 14.7 mg/m3 for 1 day to 2 years. The human studies covered primarily chrysotile (Hammond), mixed asbestos types (Henderson and Enterline), chrysotile (Dement), amosite (Seidman) and chrysotile (McDonald). Risks were projected for 0.5 f/cm3 over 45 years (22.5 f-yr/cm3 cumulative exposure).
• Main results:
  • The geometric mean of the projected lifetime lung cancer risks from the five human studies was 0.0146. For the rat data it was 0.0179 without the surface-area adjustment and 0.0122 with it.
  • When the McDonald et al. mining and milling study was excluded, the geometric mean of the human estimates was 0.031.
  • Projected risks across the rat fiber-type groups varied within 2.4-fold without the surface-area calculation and within 2.25-fold with it.
  • Projected risks from the human studies varied by a factor of 236, or by a factor of 46 when the mining and milling study was excluded.
  • The projected risk for the Hammond et al. study, assuming general-population smoking rates, was 0.0216.
  • The authors adjusted the Hammond et al. dose-response curve to approximate nonsmoking asbestos workers (about one-tenth of the risk). This gave a projected risk of 2.2 x 10 to the minus 3, which was 6 to 8 times less than the rat projections calculated on a cumulative exposure basis.
  • Projected on a concentration-per-day ('unit dose') basis, the rat lifetime risk was 0.4 to 0.5 x 10 to the minus 3. This is below the lowest human estimate and below the nonsmoker estimate.
• The authors' conclusion: The authors concluded that the analysis suggests some validity in using animal-to-human lung cancer risk extrapolations for asbestos. They added that the issue needs continued examination.
• Limitations the authors state:
  • The animal risk calculations may overstate risk, depending on the dosage concept used (cumulative exposure versus lifetime average daily dose).
  • Available data do not allow firm statements about comparative doses reaching the lung tissue in rats and humans.
  • A single mass-to-fiber conversion factor was used, although different factors may be appropriate for crocidolite, chrysotile and amosite.
  • Extrapolating the human results to a full lifetime may overestimate relative risks at the oldest ages. At low doses, risks may be under- or overestimated.
  • Information is lacking on factors relevant to risk assessment, including target tissue dose, unit conversion methods and smoking-asbestos interactions.

Topics

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

Medical terms in this study, explained in our Lexicon: Lung Cancer, Dose-response relationship, Amosite, Anthophyllite, Crocidolite, Chrysotile, Epidemiology, Cumulative Exposure.

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