Abstract

http://ssrn.com/abstract=943194
 
 

References (23)



 


 



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


Robert M. Park


Government of the United States of America - National Institute for Occupational Safety and Health

Leslie T. Stayner


University of Illinois at Chicago - Epidemiology/Biostatistics


Risk Analysis, Vol. 26, No. 1, pp. 79-88, February 2006

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 mg/m(3) CrO(3) (16 mg/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)(.08) 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.

Number of Pages in PDF File: 10

Accepted Paper Series


Date posted: November 7, 2006  

Suggested Citation

Park, Robert M. and Stayner, Leslie T., A Search for Thresholds and Other Nonlinearities in the Relationship Between Hexavalent Chromium and Lung Cancer. Risk Analysis, Vol. 26, No. 1, pp. 79-88, February 2006. Available at SSRN: http://ssrn.com/abstract=943194 or http://dx.doi.org/10.1111/j.1539-6924.2006.00709.x

Contact Information

Robert M. Park (Contact Author)
Government of the United States of America - National Institute for Occupational Safety and Health ( email )
Education and Information Division
4676 Columbia Parkway
Cincinnati, OH 45226
United States
(513) 533-8572 (Phone)
(513) 533-8224 (Fax)
Leslie T. Stayner
University of Illinois at Chicago - Epidemiology/Biostatistics ( email )
Chicago, IL 60612
United States
(312) 355-3692 (Phone)
HOME PAGE: http://www.srl.uic.edu/gcsrm/faculty.htm
Feedback to SSRN


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References:  23

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