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Workplace
Original research
Benzene exposure and risk of benzene poisoning in Chinese workers
  1. Roel Vermeulen1,
  2. Lützen Portengen1,
  3. Guilan Li2,
  4. Ethel S Gilbert3,
  5. Graça M Dores4,
  6. Bu-Tian Ji5,
  7. Richard Hayes6,
  8. Sognian Yin7,
  9. Nathaniel Rothman5,
  10. Martha S Linet3,
  11. Qing Lan5
  12. on behalf of the Chinese Center for Disease Control and Prevention—U.S. National Cancer Institute Benzene Study Group
    1. 1Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
    2. 2Institute of Occupational Health and Injuries, Chinese Center for Disease Control and Prevention, Beijing, China
    3. 3Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
    4. 4Analytic Epidemiology Branch, Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA
    5. 5Occupational and Environmental Epidemiology Branch, National Cancer Institute Division of Cancer Epidemiology and Genetics, Bethesda, Maryland, USA
    6. 6Division of Epidemiology, Department of Population Health, New York University Grossman School of Medicine, New York, New York, USA
    7. 7Chinese Center for Disease Control and Prevention, Beijing, Beijing, China
    1. Correspondence to Dr Roel Vermeulen, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands; r.c.h.vermeulen{at}uu.nl

    Abstract

    Objectives Benzene is a known haematoxin and leukemogen that can cause benzene poisoning (BP), that is, a persistent reduction in white cell counts that is strongly associated with increased risk of lymphohaematopoietic malignancies. Data are needed on the exposure–response, particularly at low doses and susceptible populations for clinical and regulatory purposes.

    Methods In a case-cohort study among 110 631 Chinese workers first employed 1949–1987 and followed up during 1972–1999, we evaluated BP risk according to benzene exposure level and investigated risk modification by subject (sex, attained age) and exposure-related factors (latency, exposure windows, age at first benzene exposure, coexposure to toluene) using excess relative risk and excess absolute risk models.

    Results There were 538 BP cases and 909 benzene-exposed referents. The exposure metric with best model fit was cumulative benzene exposure during a 5-year risk window, followed by a 9-month lag period before BP diagnosis. Estimated excess absolute risk of BP at age 60 increased from 0.5% for subjects in the lowest benzene exposure category (>0 to 10 ppm-years) to 5.0% for those in the highest category (>100 ppm-years) compared with unexposed subjects. Increased risks were apparent at low cumulative exposure levels and for workers who were first exposed at <30 years of age.

    Conclusions Our data show a clear association between benzene exposure and BP, beginning at low cumulative benzene exposure levels with no threshold, and with higher risks for workers exposed at younger ages. These findings are important because BP has been linked to a strongly increased development of lymphohaematopoietic malignancies.

    • benzene
    • hematology
    • leukemia
    • risk assessment
    • epidemiology

    Data availability statement

    Data are available on reasonable request.

    https://doi.org/10.1136/oemed-2021-108155

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      Data availability statement

      Data are available on reasonable request.

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      Footnotes

      • Collaborators The following are members of the Chinese Centre for Disease Control and Prevention – U.S. National Cancer Institute Benzene Study Group: Cheng-yu Ding (Institute for Health Inspection and Supervision, Jinzhou Municipal Health Bureau, Jinzhou, China), Graça M. Dores (Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland and U.S. Food and Drug Administration, Silver Spring, Maryland, both in USA), Yuan Gao (Chengdu Centre for Disease Control and Prevention, Chengdu, China), Ethel S. Gilbert (Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA), Richard B. Hayes (Division of Epidemiology, Department of Population Health, New York University, School of Medicine, New York, New York, USA), Bu-tian Ji (Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA), Qing Lan (Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA), Gui-lan Li (Co-Principal Investigator, National Institute of Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, China), Gui-zhen Li (Institute for Health Inspection and Supervision, Shenyang Municipal Health Bureau, Shenyang, China), Martha S. Linet (Co-Principal Investigator, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA), Lian-Cui Liu (Kaifeng Centre for Disease Control and Prevention, Kaifeng, China), Yu-ne Ni (Institute for Health Inspection and Supervision, Shanghai Municipal Health Bureau, Shanghai, China), Xin-hua Niu (Zhengzhou Institute for Occupational Disease Control and Prevention, Zhengzhou, China), Lutzen Portengen (Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands), Nathaniel Rothman (Co-Principal Investigator, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA), Gui-fen Sun (Institute for Health Inspection and Supervision, Heilongjiang Province Health Bureau, Harbin, China), Qiang Tang (Institute for Health Inspection and Supervision, Chongqing Municipal Health Bureau, Chongqing, China), Hao-yuan Tian (National Institute of Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, China), Roel Vermeulen (Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands), Lu-wu Xiao (Guangzhou No. 12 People’s Hospital, Guangzhou, China), Song-nian Yin (Co-Principal Investigator, National Institute of Occupational Health and Poison Control, Chinese Centre for Disease Control and Prevention, Beijing, China), Hong-bin Zhao (Luoyang Centre for Disease Control and Prevention, Luoyang, China), Guang-fa Zhou (Tianjin Occupational Disease Hospital (Tianjin No. 3 Hospital), Tianjin, China), Jie-sen Zhou (Nanchang Centre for Disease Control and Prevention, Nanchang, China).

      • Contributors RV, GL, GMD, B-TJ, RH, SY, NR, MSL and QL designed and executed the study. GMS, MSL, GL and GMD evaluated the clinical information. LP and ESG performed the statistical analyses. RV and LP developed the first draft of the manuscript, and edited the paper according to coauthors’ suggestions. All authors contributed to the final draft of the manuscript. RV, LP, NR, MSL and QL accepted full responsibility for the finished article, had access to all data and controlled the decision to publish. RV is the guarantor of the paper.

      • Funding This project was supported by the National Institutes of Health Intramural Research PProgramme (Grant No: NA).

      • Disclaimer The content of this publication does not necessarily reflect the views or policies of the US Food and Drug Administration and Department of Health and Human Services, nor does mention of trade names, commercial products, or organisations imply endorsement by the US government.

      • Competing interests None declared.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.