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Search for thresholds and other non-linearities in the hexavalent chromium - lung cancer exposure response.
Am J Epidemiol 2005 Jun; 161(11)(Suppl):S87
This study investigated non-linear features of the exposure response including threshold and dose rate effects, and other attributes, in a cohort of 2357 chemical workers with 122 lung cancer deaths. Variations in the construction of the cumulative exposure thresholds, exposure intensity thresholds, variable dose-rate effects, and a declining burden of accumulated future risk. Using Poisson regression, a simple two-stage carcinogenesis model was rejected. The best fitting models had no threshold for exposure intensity and the study had sufficient power to rule out thresholds as large as 50 ug/m3 CrO3 (likelihood ratio test, p<.03) (the current OSHA standard permits exposures up to 100 ug/m3 CrO3. For cumulative exposure, slightly better fitting models were observed for thresholds of 0.05-0.5 mg-yr/m3 (as CrO3) but the fits were not statistically significantly better than a model without a threshold. Cumulative exposure thresholds as large as 1.5 mg-yr/m3 CrO3 were excluded (likelihood ratio test, p<.01) (current standard permits lifetime cumulative exposures up to 4.5 mg-yr/m3 CrO3). Departure from linearity of the dose rate effect was negative, corresponding to intensity raised to the 0.8 power but this was not statistically significant. Models with declining risk burdens based on half-lives ranging 0.1 to 40 years fit less well than assuming a constant burden. This examination of non-linear features of the hexavalent chromium - lung cancer response supports the use of the traditional (lagged) cumulative exposure paradigm: no threshold, linearity in intensity, and constant increment in risk following an exposure.
Chromium-compounds; Cancer; Lung-cancer; Exposure-assessment; Hexavalent-chromium-compounds; Risk-analysis; Risk-factors; Pulmonary-system-disorders; Models; Respiratory-system-disorders; Statistical-analysis; Epidemiology
Issue of Publication
American Journal of Epidemiology
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division