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The Effect of Uncertainty in Exposure Estimation on the Exposure-Response Relation between 1,3-Butadiene and Leukemia
Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, MI 48201, USA
University of Alabama at Birmingham School of Public Health, Department of Epidemiology, Birmingham, AL 35294, USA
Centers for Disease Control and Prevention, Division of Reproductive Health, Atlanta, GA 30341, USA
University of Minnesota School of Public Health, Division of Environmental Health Sciences, Minneapolis, MN 55455, USA
* Author to whom correspondence should be addressed.
Received: 16 July 2009; Accepted: 8 September 2009 / Published: 11 September 2009
Abstract: Abstract: In a follow-up study of mortality among North American synthetic rubber industry workers, cumulative exposure to 1,3-butadiene was positively associated with leukemia. Problems with historical exposure estimation, however, may have distorted the association. To evaluate the impact of potential inaccuracies in exposure estimation, we conducted uncertainty analyses of the relation between cumulative exposure to butadiene and leukemia. We created the 1,000 sets of butadiene estimates using job-exposure matrices consisting of exposure values that corresponded to randomly selected percentiles of the approximate probability distribution of plant-, work area/job group-, and year specific butadiene ppm. We then analyzed the relation between cumulative exposure to butadiene and leukemia for each of the 1,000 sets of butadiene estimates. In the uncertainty analysis, the point estimate of the RR for the first non zero exposure category (>0–<37.5 ppm-years) was most likely to be about 1.5. The rate ratio for the second exposure category (37.5–<184.7 ppm-years) was most likely to range from 1.5 to 1.8. The RR for category 3 of exposure (184.7–<425.0 ppm-years) was most likely between 2.1 and 3.0. The RR for the highest exposure category (425.0+ ppm-years) was likely to be between 2.9 and 3.7. This range off RR point estimates can best be interpreted as a probability distribution that describes our uncertainty in RR point estimates due to uncertainty in exposure estimation. After considering the complete probability distributions of butadiene exposure estimates, the exposure-response association of butadiene and leukemia was maintained. This exercise was a unique example of how uncertainty analyses can be used to investigate and support an observed measure of effect when occupational exposure estimates are employed in the absence of direct exposure measurements.
Keywords: 1,3-butadiene; epidemiology; methods; leukemia; workplace exposures; uncertainty analysis
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Graff, J.J.; Sathiakumar, N.; Macaluso, M.; Maldonado, G.; Matthews, R.; Delzell, E. The Effect of Uncertainty in Exposure Estimation on the Exposure-Response Relation between 1,3-Butadiene and Leukemia. Int. J. Environ. Res. Public Health 2009, 6, 2436-2455.
Graff JJ, Sathiakumar N, Macaluso M, Maldonado G, Matthews R, Delzell E. The Effect of Uncertainty in Exposure Estimation on the Exposure-Response Relation between 1,3-Butadiene and Leukemia. International Journal of Environmental Research and Public Health. 2009; 6(9):2436-2455.
Graff, John J.; Sathiakumar, Nalini; Macaluso, Maurizio; Maldonado, George; Matthews, Robert; Delzell, Elizabeth. 2009. "The Effect of Uncertainty in Exposure Estimation on the Exposure-Response Relation between 1,3-Butadiene and Leukemia." Int. J. Environ. Res. Public Health 6, no. 9: 2436-2455.