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.
Highlights
Assessment of exposure in epidemiologic studies is especially difficult for historical periods when worker or workplace monitoring data were scarce
Percentiles chosen for each primary work area/job group in the six plants ranged from a minimum value of 1 to a maximum of 99
In our study of mortality among North American synthetic rubber industry workers, we assessed the impact of potential systematic error due to problems with historical exposure estimation on the observed association between butadiene and leukemia
Summary
Assessment of exposure in epidemiologic studies is especially difficult for historical periods when worker or workplace monitoring data were scarce. Exposure typically must be estimated using information on subjects’ history of employment by production area, job title, task, duration of employment or a combination of these [1,2] In these situations misclassification of subjects by exposure is inevitable, error in study results is likely and the direction of the error may be unpredictable [3,4,5,6,7,8,9,10]. We selected one subject’s work history, with its calendar year and work area/job group combinations and the corresponding butadiene estimates used in our main analyses.
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