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

Details

• Personal Author:
  Park RM ; Stayner, Leslie T.
• Description:
  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 mug/m(3) CrO(3) (16 mug/m(3) 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/m(3) (as CrO(3)) with and without an exposure-race interaction term, respectively. With the best model, cumulative exposure thresholds as large as 0.4 mg-yr/m(3) CrO(3) 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. [Description provided by NIOSH]
• Subjects:
  Chromium Environmental Monitoring Lung Lung Diseases Mortality Neoplasms Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Cancer Chromium-compounds Exposure-assessment Lung-cancer Models Mortality-data Mortality-rates Occupational-exposure Pulmonary-system-disorders Respiratory-system-disorders Risk-analysis Risk-factors Worker-health Workers

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• ISSN:
  0272-4332
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  EID - Education and Information Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  79-88
• Volume:
  26
• Issue:
  1
• NIOSHTIC Number:
  nn:20029720
• Citation:
  Risk Anal 2006 Feb; 26(1):79-88
• Contact Point Address:
  Robert M. Park, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Education and Information Division, MS C-15, 4676 Columbia Parkway, Cincinnati, OH 45226
• Email:
  rhp9@cdc.gov
• CAS Registry Number:
  Chromium(6+) (CAS RN 18540-29-9)
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Risk Assessment Methods
• Peer Reviewed:
  True
• Source Full Name:
  Risk Analysis
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:09e5c4d733cc6f54aac99e5f5ce1016a71825883685ddc8934e0049fc618c8d6eaba6a2320e31baf81f220ec5eb98e68cc21c6edff1e3ecf1e1f0f14eb03d176
• Download URL:
  https://stacks.cdc.gov/view/cdc/190642/cdc_190642_DS1.pdf
• File Type:
  [PDF - 225.60 KB ]