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A Search for Thresholds and Other Nonlinearities in the Relationship Between Hexavalent Chromium and Lung Cancer

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  • Robert M. Park
  • Leslie T. Stayner

Abstract

The exposure‐response relationship for airborne hexavalent chromium exposure and lung cancer mortality is well described by a linear relative rate model. However, categorical analyses have been interpreted to suggest the presence of a threshold. This study investigates nonlinear features of the exposure response in a cohort of 2,357 chemical workers with 122 lung cancer deaths. In Poisson regression, a simple model representing a two‐step carcinogenesis process was evaluated. In a one‐stage context, fractional polynomials were investigated. Cumulative exposure dose metrics were examined corresponding to cumulative exposure thresholds, exposure intensity (concentration) thresholds, dose‐rate effects, and declining burden of accumulated effect on future risk. A simple two‐stage model of carcinogenesis provided no improvement in fit. The best‐fitting one‐stage models used simple cumulative exposure with no threshold for exposure intensity and had sufficient power to rule out thresholds as large as 30 μg/m3 CrO3 (16 μg/m3 as Cr+6) (one‐sided 95% confidence limit, likelihood ratio test). Slightly better‐fitting models were observed with cumulative exposure thresholds of 0.03 and 0.5 mg‐yr/m3 (as CrO3) with and without an exposure‐race interaction term, respectively. With the best model, cumulative exposure thresholds as large as 0.4 mg‐yr/m3 CrO3 were excluded (two‐sided upper 95% confidence limit, likelihood ratio test). A small departure from dose‐rate linearity was observed, corresponding to (intensity)0.8 but was not statistically significant. Models in which risk‐inducing damage burdens declined over time, based on half‐lives ranging from 0.1 to 40 years, fit less well than assuming a constant burden. A half‐life of 8 years or less was excluded (one‐sided 95% confidence limit). Examination of nonlinear features of the hexavalent chromium‐lung cancer exposure response in a population used in a recent risk assessment supports using the traditional (lagged) cumulative exposure paradigm: no intensity (concentration) threshold, linearity in intensity, and constant increment in risk following exposure.

Suggested Citation

  • Robert M. Park & Leslie T. Stayner, 2006. "A Search for Thresholds and Other Nonlinearities in the Relationship Between Hexavalent Chromium and Lung Cancer," Risk Analysis, John Wiley & Sons, vol. 26(1), pages 79-88, February.
    • Handle: RePEc:wly:riskan:v:26:y:2006:i:1:p:79-88
    DOI: 10.1111/j.1539-6924.2006.00709.x
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    References listed on IDEAS

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    1. Robert M. Park & James F. Bena & Leslie T. Stayner & Randall J. Smith & Herman J. Gibb & Peter S. J. Lees, 2004. "Hexavalent Chromium and Lung Cancer in the Chromate Industry: A Quantitative Risk Assessment," Risk Analysis, John Wiley & Sons, vol. 24(5), pages 1099-1108, October.
    2. Casey Crump & Kenny Crump & Eric Hack & Rose Luippold & Kenneth Mundt & Elizabeth Liebig & Julie Panko & Dennis Paustenbach & Deborah Proctor, 2003. "Dose‐Response and Risk Assessment of Airborne Hexavalent Chromium and Lung Cancer Mortality," Risk Analysis, John Wiley & Sons, vol. 23(6), pages 1147-1163, December.
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