One agent, many diseases: exposure-response data and comparative risks of different outcomes following silica exposure

Our plain-English summary of One agent, many diseases: exposure-response data and comparative risks of different outcomes following silica exposure, by K. Steenland (American Journal of Industrial Medicine, 2005).

The study

• Author: K. Steenland
• Journal: American Journal of Industrial Medicine
• Published: 2005;48(1):16-23
• Cited by: 94 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Evidence in recent years indicates that silica causes lung cancer, and probably renal disease, in addition to its well-known relationship to silicosis. There is also suggestive evidence that silica can cause arthritis and other auto-immune diseases. Silica has, therefore, joined a handful of other toxic exposures such as tobacco smoke, dioxin, and asbestos which cause multiple serious diseases.

Methods: The available exposure-response data for silica and silicosis, lung cancer, and renal disease are reviewed. We compare the corresponding excess risks (or absolute risks in the case of silicosis) of death or disease incidence by age 75 for these three diseases, subsequent to a lifetime (45 years) of exposure to silica at current US standard (0.1 mg/m(3) respirable crystalline silica).

Results: The absolute risk of silicosis, as defined by small opacities greater than or equal to ILO classification 1/1 on an X-ray, ranges from 47% to 77% in three cohort studies with adequate follow-up after employment. The absolute risk of death from silicosis is estimated at 1.9% (0.8%-2.9%), based on a pooled analysis of six cohort studies. The excess risk of lung cancer death, assuming US male background rates, is 1.7% (0.2%-3.6%), based on a pooled analysis of ten cohort studies. The excess risk of end-stage renal disease (assuming male background rates) is 5.1% (2.2%-7.3%), based on a single cohort. The excess risk of death from renal disease is estimated to be 1.8% (0.8%-9.7%), based on a pooled analysis of three cohorts.

Conclusions: Keeping in mind that the usual OSHA acceptable excess risk of serious disease or death for workers is 0.1%, it is clear that the current standard is far from sufficiently protective of workers' health. Perhaps surprisingly, kidney disease emerges as perhaps a higher risk than either mortality from silicosis or lung cancer, although the data are based on fewer studies.

In plain English

This review estimated men's risks by age 75 from silica exposure-response data, assuming 45 years at the US standard of 0.1 mg/m3 respirable crystalline silica. In three cohort studies with post-employment follow-up, the risk of X-ray silicosis (small opacities, ILO 1/1 or more) was 47% to 77%; opacities need not mean symptoms. Pooled data gave a 1.9% (0.8% to 2.9%) risk of silicosis death and a 1.7% (0.2% to 3.6%) excess risk of lung cancer death, above a 7.5% background. Among 4,620 industrial sand workers, 23 developed end-stage kidney disease versus 11.7 expected. Its estimated excess risk was 5.1%, given as 3.3% to 7.3% in the main text but 2.2% to 7.3% in the abstract. Excess risk of kidney disease death was 1.8% (0.8% to 9.7%). Against OSHA's usual acceptable excess risk of 0.1%, the author concluded the standard was far from sufficiently protective. The author judged kidney disease perhaps the most common serious outcome apart from X-ray changes, though on fewer studies. The author noted silicosis would be the largest risk if X-ray changes often became symptomatic.

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 exposure-response data for silica and silicosis, lung cancer and renal disease, largely drawn from the author's own earlier cohort and pooled analyses, with calculation of lifetime risks at the US standard. Asbestos is mentioned only as another agent that causes several diseases.
• Who was studied: Workers in previously published cohorts. Silicosis X-ray data came from three cohort studies with post-employment follow-up. Silicosis mortality came from an IARC pooled study of 18,000 workers in six cohorts (170 deaths). Lung cancer came from an IARC pooled analysis of ten cohorts with 65,000 workers and over 1,000 lung cancer deaths. End-stage renal disease came from a cohort of 4,620 US industrial sand workers. Renal disease mortality came from three pooled cohorts (n = 13,000). Risks were calculated for men only.
• Exposure: Respirable crystalline silica. Risks were estimated for a 45-year working lifetime at the US standard of 0.1 mg/m3, and also at a tenth of that level (0.01 mg/m3).
• Main results:
  • Risk of silicosis (small opacities, ILO 1/1 or more, on X-ray) after 45 years at 0.1 mg/m3 was 47% to 77%, based on three cohort studies with adequate post-employment follow-up.
  • Estimated absolute risk of death from silicosis after a lifetime at 0.1 mg/m3 was 1.9% (0.8%–2.9%), based on a pooled analysis of six cohort studies.
  • In the ten-cohort pooled analysis, lung cancer odds ratios by quintile of cumulative silica exposure were 1.0, 1.0 (0.9–1.3), 1.3 (1.1–1.7), 1.5 (1.2–1.9) and 1.7 (1.3–2.1).
  • Excess lifetime risk of lung cancer death (to age 75) after 45 years at 0.1 mg/m3 was 1.7% (0.2%–3.6%), above a background risk of 7.5%.
  • Among 4,620 industrial sand workers, 23 cases of end-stage renal disease were observed.
  • The 23 end-stage renal disease cases in the industrial sand cohort compared with 11.7 expected, giving a standardized incidence ratio of 1.97 (1.25–2.96).
  • Estimated excess risk of end-stage renal disease by age 75 after a 45-year working lifetime at the OSHA standard was 5.1% (3.3–7.3%) in the main text and Table VI.
  • The article's own abstract gives the same 5.1% excess risk of end-stage renal disease with a different range, 2.2%–7.3%.
  • Estimated excess risk of death from renal disease (underlying cause) after 45 years at the OSHA standard was 1.8% (0.8–9.7%), based on three pooled cohorts.
  • The author found that kidney disease emerged as perhaps the most common serious chronic outcome of silica exposure, apart from X-ray findings of small opacities.
  • The author added that if X-ray changes frequently progress to symptomatic silicosis, silicosis would represent the largest risk.
  • Even at a tenth of the current standard, the estimated risks remained above OSHA's usual permitted risk.
• The authors' conclusion: The author concluded that, given OSHA's usual acceptable excess risk of 0.1%, the current US silica standard is far from sufficiently protective of workers' health.
• Limitations the authors state:
  • Small opacities on X-ray do not necessarily mean symptomatic disease.
  • The kidney disease estimates rest on fewer studies.
  • The author described the overall evidence that silica causes kidney disease as too sparse to call conclusive.
  • Risks were calculated only for men, because the cohorts contained negligible numbers of women.
  • In one South African study, exposures were underestimated, which led to an overestimate of its exposure-response coefficient.

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, Silicosis, Crystalline, ILO Classification, Meta-Analysis, Background Rate, OSHA.

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• Silica and asbestos exposure in ANCA-associated vasculitis with pulmonary involvement — Z. Rihova, D. Maixnerova, et al. (2005)
• Re: "Dose-response associations of silica with nonmalignant respiratory disease and lung cancer mortality in the diatomaceous earth industry" — G.W. Gibbs (1998)
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