Systematic review of the scientific evidence of the pulmonary carcinogenicity of talc

Our plain-English summary of Systematic review of the scientific evidence of the pulmonary carcinogenicity of talc, by H.N. Lynch, D.J. Lauer, W.J. Thompson, et al (Frontiers in Public Health, 2022).

The study

• Authors: H.N. Lynch, D.J. Lauer, W.J. Thompson, O. Leleck, R.D. Freid, J. Collins, K. Chen, A.M. Ierardi, A.M. Urban, M.A. Cappello, P. Boffetta, K.A. Mundt
• Journal: Frontiers in Public Health
• Published: 2022;10:989111
• Type of article: Systematic review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We conducted a systematic review to assess the potential pulmonary carcinogenicity of inhaled talc in humans. Our systematic review methods adhere to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and incorporated aspects from the US Institute of Medicine (IOM) and several United States (US) Environmental Protection Agency (EPA) frameworks for systematic reviews. A comprehensive literature search was conducted. Detailed data abstraction and study quality evaluation, adapting the US Toxic Substances Control Act (TSCA) framework, were central to our analysis. The literature search and selection process identified 23 primary studies that assessed exposure to talc and pulmonary cancer risks in humans (n = 19) and animals (n = 3). Integrating all streams of evidence according to the IOM framework yielded classifications of suggestive evidence of no association between inhaled talc and lung cancer and pleural mesothelioma at human-relevant exposure levels.

Copyright © 2022 Lynch, Lauer, Thompson, Leleck, Freid, Collins, Chen, Ierardi, Urban, Cappello, Boffetta and Mundt.

In plain English

This was a systematic review. Their search on talc and all cancers yielded 716 publications, from which they selected studies on lung cancer or pleural mesothelioma. They included 19 epidemiological studies and three animal studies. The human studies covered talc miners and millers in New York State, Italy, Norway, France, Austria and Vermont. The authors found no epidemiological studies of consumer talc use. Some New York mines were reported to produce talc with amphibole minerals including tremolite and anthophyllite. None of the 17 cohort studies identified an increased risk of pleural or peritoneal mesothelioma. Among the most recent cohort updates, only one New York cohort reported a statistically significant lung cancer excess (SMR 2.32; 95% CI 1.57 to 3.29). In that cohort, risk did not increase with cumulative exposure. In one animal study, female rats given very high doses of micronized talc had more lung tumors. The authors said these doses appeared to cause particle overload, which limited extrapolation to humans. The authors concluded there was suggestive evidence of no association between inhaled talc and lung cancer and pleural mesothelioma at human-relevant exposure levels. They noted smoking was not adequately considered in lung cancer studies.

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: Systematic review of epidemiological, animal and mechanistic studies. It followed PRISMA, rated study quality with an adapted US EPA TSCA framework, and classified conclusions with the US Institute of Medicine framework.
• Who was studied: Studies found by a PubMed search on talc exposure and all cancers (April, updated September 2021), which yielded 716 publications, plus supplemental searches. Included were 19 epidemiological studies (17 cohort study publications and two nested case-control studies) and three animal studies addressing pulmonary cancers. The human studies were of talc miners and millers in New York State, Italy, Norway, France, Austria and Vermont. Cohorts ranged from about 400 to over 1,700 workers.
• Exposure: Inhaled talc in mining and milling. Italian, Norwegian, French and Austrian talcs were described as non-asbestiform, and Vermont talc as free of asbestiform mineral. Some upstate New York mines were reported to produce talc with asbestiform or non-asbestiform amphibole minerals including tremolite and anthophyllite. The animal studies used baby powder, Italian talc and micronized talc.
• Main results:
  • None of the 17 cohort studies of talc miners and millers identified an increased risk of malignant pleural or peritoneal mesothelioma.
  • Among the most recent cohort updates, only the New York cohort of Honda et al. reported a statistically significant excess of lung cancer (SMR = 2.32; 95% CI: 1.57 to 3.29).
  • In an earlier New York analysis (Lamm et al.) of 705 white men employed between 1957 and 1977, lung cancer mortality was statistically significantly elevated among workers employed less than 1 year (SMR = 3.17, based on six lung cancer deaths). Those authors attributed the excess to previous employment and smoking.
  • Lung cancer mortality was slightly elevated but not statistically significant in French (SMR = 1.23; 95% CI: 0.76 to 1.89) and Vermont (SMR = 1.44; 95% CI: 0.98 to 2.03) talc miners and millers.
  • Lung cancer mortality was close to unity in Austrian (SMR = 1.06; 95% CI: 0.43 to 2.19), Italian (SMR = 1.02; 95% CI: 0.82 to 1.27) and Norwegian (SIR = 1.17; 95% CI: 0.73 to 1.79) talc miners and millers.
  • In the New York cohort of Honda et al., lung cancer risk did not increase with increasing cumulative exposure.
  • In the French and Austrian nested case-control analysis, lung cancer showed no association with increasing cumulative talc exposure after adjustment for smoking, quartz exposure and underground work.
  • A power analysis by Ierardi and Marsh estimated that the pooled cohorts had 59% power to detect a 2.5-fold or greater increased risk of mesothelioma, and 78% power to detect a 3.0-fold or greater increased risk.
  • All cohorts except the Norwegian one reported statistically significant excess mortality from pneumoconiosis.
  • In the National Toxicology Program study, female rats had an increased incidence of lung alveolar/bronchiolar adenomas and carcinomas. The authors said the lung tumors occurred at very high doses of micronized talc that appeared to cause particle overload, which limited extrapolation to relevant human exposures. Mice showed no evidence of carcinogenic activity.
  • In the Wagner et al. rat study, two adenomas (not considered cancerous) were seen in talc-exposed rats, 13 lung tumors in chrysotile-exposed rats, and one adenoma in air-exposed controls.
  • Talc was negative in all available genotoxicity assays.
• The authors' conclusion: The authors concluded that the evidence was suggestive of no association between inhaled talc and lung cancer and pleural mesothelioma at human-relevant exposure levels.
• Limitations the authors state:
  • Smoking was not adequately considered in the lung cancer studies.
  • Information on cohort members' prior employment was inadequate, so possible prior occupational asbestos exposure could not be determined.
  • No epidemiological studies of consumer use of talc or talcum powder products were found.
  • Mechanistic information was scarce.
  • Some of the individual cohorts were small.
  • The positive animal study used micronized talc. The authors said micronized talc is not used in cosmetic talcum powder, which may limit how far the results apply.
  • Under the classification framework the authors used, the possibility of a very small elevation in risk at the exposure levels studied can never be excluded.
  • The authors acknowledged that their review approach could be further refined.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Talc and vermiculite.

Medical terms in this study, explained in our Lexicon: Systematic Review, Talc, Toxic Substances Control Act (TSCA), Lung Cancer, Pleural Mesothelioma.

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