Benzene risk assessment: does new evidence on myelodysplastic syndrome justify a new approach?

Abstract

Epidemiologic findings play an important role in benzene risk assessment, which is utilized to guide the selection of recommended benzene exposure levels to prevent adverse health effects. For decades, excess leukemia risk, especially that in the Pliofilm^® cohort, has been the focus of benzene risk assessment. While more stringent benzene standards, often ≤1 ppm, have been promulgated to protect workers from developing leukemia, recent epidemiologic studies have reported elevated risk of myelodysplastic syndrome (MDS). This report aims to examine whether the use of new data on MDS is scientifically warranted in future benzene risk assessments. First, we reviewed current benzene guidelines, regulations, and underlying risk assessments in developed countries. Second, we examined current epidemiologic literature on benzene and MDS, which identified seven studies with simultaneous measures of MDS risk and benzene exposure and 17 studies on MDS in populations potentially exposed to benzene. Next, we examined the potential of the MDS data to serve as the basis of future benzene risk assessments, by comparing its quality and risk estimates with those used in current benzene standards. We conclude from the current literature that there is strong evidence that MDS can be caused by benzene, and the MDS data from the pooled petroleum study should be further examined in future benzene risk assessments. We recommend that future MDS-based benzene risk assessment use total MDS as the endpoint, take into consideration the full exposure period, and examine a range of benzene exposure metrics, including the role of peak, intermittent benzene exposures.

Keywords:

• Benzene
• myelodysplastic syndrome
• leukemia
• risk assessment
• guideline
• regulation
• occupational exposure
• pooled petroleum study
• Pliofilm
• epidemiologic studies
• review
• cancer

Acknowledgements

The authors would like to thank the five expert reviewers who were identified by the Editor and anonymous to the authors for providing valuable comments on revising the manuscript. The authors would like to acknowledge Kate Creegan for developing the search algorithms used in the paper, Min Chen for providing insights on the reality checks for consistency of MDS data, Jeff Lewis and Colin North for very helpful comments.

Declaration of interest

The authors report no financial interest or benefit that will arise from the direct application of the research. The initial research was performed at ExxonMobil Biomedical Sciences, Inc. (EMBSI), where Ms. Li was employed as an intern and Dr. Schnatter was employed as a full-time employee. The American Petroleum Institute (API) and EMBSI each provided partial financial support for the initial work of the authors. An initial manuscript for publication was generated after Ms. Li returned to the University of Michigan. Ms. Li did not receive any financial support and Dr. Schnatter received financial support from EMBSI for the initial manuscript. The manuscript was further developed, without financial support, while Ms. Li was at University of Michigan and Dr. Schnatter at EpiSolutions, LLC. The authors have sole responsibility for the writing and content of the paper. The synthesis performed and the conclusions drawn are exclusively those of the authors and not necessarily those of their current or former employers. EMBSI reviewed and approved the manuscript prior to submission and the API did not review the manuscript prior to submission. Within the last 5 years, Ms. Li has not participated as an expert on any legal or regulatory matters related to the contents of the paper; whereas Dr. Schnatter, during his time at EMBSI, has provided expert advice to in-house legal contacts on legal matters and to trade associations (API, Conservation of Clean Air and Water in Europe, and the Lower Olefins and Aromatics REACH Consortium) on regulatory matters related to the contents of this paper.

Supplementary material

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