The National Institute of Occupational Safety and Health (NIOSH) recently completed a vital status update adding 6 years of observation on the rubber workers known as the Pliofilm cohort. Using traditional standardized mortality ratio (SMR) analysis, we investigate the impact of the additional information gathered in the NIOSH update. We also compare the effect of using three sets of job-, plant-, and year-specific exposure estimates on the evaluation of benzene's leukemogenicity. The lack of any additional cases of multiple myeloma does not support trends toward elevated risks for this endpoint (as had been observed earlier), and there is no indication of increased incidences of solid tumors (as predicted by animal studies). Qualitatively, which exposure estimates are used does not alter the conclusions. The data added in the update did not greatly modify the estimated relative risk of leukemia associated with benzene exposure, but did confirm previous findings that occupational exposure to high concentrations had leukemogenic potential. The fact that leukemia has not been observed in any individual who started employment in Pliofilm production after 1950 suggests that the observed leukemia cases could be a response to very high levels of benzene exposure that occurred during the early years of this manufacturing process.

The detailed work histories of the individual workers composing the Pliofilm cohort represent a unique resource for estimating the dose-response for leukemia that may follow occupational exposure to benzene. In this paper, we report the results of analyzing the updated Pliofilm cohort using the proportional hazards model, a more sophisticated technique that uses more of the available exposure data than the conditional logistic model used by Rinsky et al. The more rigorously defined exposure estimates derived by Paustenbach et al. are consistent with those of Crump and Allen in giving estimates of the slope of the leukemogenic dose-response that are not as steep as the slope resulting from the exposure estimates of Rinsky et al. We consider estimates of 0.3-0.5 additional leukemia deaths per thousand workers with 45 ppm-years of cumulative benzene exposure to be the best estimates currently available of leukemia risk from occupational exposure to benzene. These risks were estimated in the proportional hazards model when the exposure estimates of Crump and Allen or of Paustenbach et al. were used to derive a cumulative concentration-by-time metric.

A reanalysis of the Pliofilm cohort was conducted incorporating six additional years of follow-up information gathered by the National Institute of Occupational Safety and Health (NIOSH) and a new set of exposure estimates developed recently. The distribution of individual worker exposures calculated with the Paustenbach exposure estimates was compared to those derived using two earlier sets of job-, plant-, and year-specific exposure estimates. A traditional standardized mortality ratio analysis and the Cox proportional hazards model were used to investigate the impact of these exposure estimates and the NIOSH updated information on evaluation of benzene's leukemogenicity. There were no additional cases of multiple myeloma or any indication of increased incidences of solid tumors. The data added in the update did not greatly modify the estimated relative risk of all leukemias associated with benzene exposure but confirmed previous findings that occupational exposure only to very high concentrations had leukemogenic potential. Leukemia has not been observed in anyone who began employment in Pliofilm production after 1950. Neither the Paustenbach nor the Crump exposures gave dose-response estimates as steep as that resulting from the Rinsky exposures.

A reanalysis of the Pliofilm cohort was conducted incorporating six additional years of follow-up information gathered by the National Institute of Occupational Safety and Health (NIOSH) and a new set of exposure estimates developed recently. The distribution of individual worker exposures calculated with the Paustenbach exposure estimates was compared to those derived using two earlier sets of job-, plant-, and year-specific exposure estimates. A traditional standardized mortality ratio analysis and the Cox proportional hazards model were used to investigate the impact of these exposure estimates and the NIOSH updated information on evaluation of benzene's leukemogenicity. There were no additional cases of multiple myeloma or any indication of increased incidences of solid tumors. The data added in the update did not greatly modify the estimated relative risk of all leukemias associated with benzene exposure but confirmed previous findings that occupational exposure only to very high concentrations had leukemogenic potential. Leukemia has not been observed in anyone who began employment in Pliofilm production after 1950. Neither the Paustenbach nor the Crump exposures gave dose-response estimates as steep as that resulting from the Rinsky exposures.

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