Shanghai Health Study (2001–2009): What was learned about benzene health effects?

Abstract

The Shanghai Health Study (SHS) was a large epidemiology study conducted as a joint effort between the University of Colorado and Fudan University in Shanghai, China. The study was funded by members of the American Petroleum Institute between 2001 and 2009 and was designed to evaluate the human health effects associated with benzene exposure. Two arms of the SHS included: an occupational-based molecular epidemiology study and several hospital-based case control studies. Consistent with historical literature, following sufficient exposure to relatively high airborne concentrations and years of exposure, the SHS concluded that exposure to benzene resulted in an increased risk of various blood and bone marrow abnormalities such as benzene poisoning, aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Non-Hodgkin lymphoma (NHL) was not significantly increased for the exposures examined in this study. Perhaps the most important contribution of the SHS was furthering our understanding of the mechanism of benzene-induced bone marrow toxicity and the importance of identifying the proper subset of MDS relevant to benzene. Investigators found that benzene-exposed workers exhibited bone marrow morphology consistent with an immune-mediated inflammatory response. Contrary to historic reports, no consistent pattern of cytogenetic abnormalities was identified in these workers. Taken together, findings from SHS provided evidence that the mechanism for benzene-induced bone marrow damage was not initiated by chromosome abnormalities. Instead, chronic inflammation, followed by an immune-mediated response, is likely to play a more significant role in benzene-induced disease initiation and progression than previously thought.

Keywords:

• Benzene
• molecular epidemiology
• exposure assessment
• aplastic anemia
• chronic myelomonocytic leukemia (CMML)
• acute myeloid leukemia (AML)
• non-Hodgkin lymphoma (NHL)
• myelodysplastic syndrome (MDS)

Acknowledgements

Dr. Sherilyn A. Gross was with ChemRisk when the bulk of this paper was written. The authors would like to extend their appreciation to Drs. A. Robert Schnatter, Patrick Kerzic, and Kristen Fedak for their review of various versions of this manuscript; Anh Le, Qian Chen, Gail Jorgensen, Susan Marcella, and the late Allan Holsomback for database management; and Thomas Armstrong, Yimei Zhou and the exposure assessment expert panel (especially Youxin Liang, Chi Zhang, and Xipeng Jin) for their contributions to the original study. Dr. Gross would like to thank the participating hospitals, including Huashan Hospital, Xinhua Hospital, Long March Hospital, Huang Pu Central District Hospital, Renji Hospital, Ruijin Hospital, Huadong Hospital, Jin An Central Hospital, No. 1 People’s Hospital, No. 5 People’s Hospital, No. 6 People’s Hospital, No. 9 People’s Hospital, Yang Pu Central Hospital, Zha Bei Central Hospital, Shu Guang Hospital, Chang Ning Central Hospital, Tong Ji Hospital, Shong Jin Central Hospital, Zhong Shan Hospital, Railway Hospital, Rong Hua Hospital, Changhai Hospital, Occupational Disease Hospital, Jiading Central Hospital, 455 Hospital, Shidong Hospital, No. 1 Baoshan Hospital, and Putuo Central Hospital. The data collection and most of the data analysis were conducted as part of the SHS. This manuscript was written independent of the Benzene Health Research Consortium and no funding of any type was received to write this manuscript.

Declaration of interest

At the time of manuscript preparation, Dr. Sherilyn Gross and Dr. Dennis Paustenbach were employees of Cardno ChemRisk, a consulting firm that provides scientific advice to the government, corporations, law firms, and various scientific/professional organizations. This manuscript was prepared and written exclusively by the authors. No outside financial support was provided to any of the authors for preparing the manuscript. The SHS was originally funded by an association of petrochemical firms in the American Petroleum Institute, the Benzene Health Research Consortium. No lawyers associated with API or litigation have read this paper prior to publication. Dr. Gross was a member of the research team from the University of Colorado, Denver, and an employee of that University at the time the study, 2001–2009. Dr. Gross conducted the work in conjunction with Fudan University, ExxonMobil Biomedical Sciences Inc., and Applied Health Sciences. The firm Cardno ChemRisk had no involvement in the SHS. Dr. Paustenbach has served as an expert in some legal cases involving benzene, but Dr. Gross has not. We understand that information assembled and analyzed in this paper may be used in regulatory deliberations, education, research, and relied upon in the courtroom.