Pooled exposure-response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study

Objectives: Silica is one of the most common occupational exposures worldwi de. In 1997 the International Agency for Research on Cancer (IARC) classifi ed inhaled crystalline silica as a human carcinogen (group 1), but acknowle dged limitations in the epidemiologic data, including inconsistencies acros s studies and the lack of extensive exposure-response data. We have conduct ed a pooled exposure-response analysis of 10 silica-exposed cohorts to inve stigate lung cancer. Methods: The pooled cohort included 65,980 workers (44,160 miners, 21,820 n ominees), and 1072 lung cancer deaths (663 miners, 409 nonminers). Follow-u p has been extended for five of these cohorts beyond published data. Quanti tative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m(3)) acros s cohorts. Results: The log of cumulative exposure, with a 15-year lag, was a strong p redictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure w ere consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend w ith odds ratios of 1.0, 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve a lso showed a monotonic increase in risk with increasing exposure. The estim ated excess lifetime risk (through age 75) of lung cancer for a worker expo sed from age 20 to 65 at 0.1 mg/m(3) respirable crystalline silica (the per missible level in many countries) was 1.1-1.7%, above background risks of 3 -6%. Conclusions: Our results support the decision by the IARC to classify inhal ed silica in occupational settings as a carcinogen, and suggest that the cu rrent exposure limits in many countries may be inadequate. These data repre sent the first quantitative exposure-response analysis and risk assessment for silica using data from multiple studies.