Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers
Background: Impairment of the hematopoietic system is one of the primary adverse health effects from exposure to benzene. We previously have shown that exposure to benzene at low levels (<1 ppm) affects the blood forming system and that these effects were proportionally stronger at lower versus h...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412023002805 |
| _version_ | 1827923373303267328 |
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| author | Roel Vermeulen Qing Lan Qingshan Qu Martha S. Linet Luoping Zhang Guilan Li Lutzen Portengen Jelle Vlaanderen Kim Sungkyoon Richard B. Hayes Songnian Yin Martyn T. Smith Stephen M. Rappaport Nathaniel Rothman |
| author_facet | Roel Vermeulen Qing Lan Qingshan Qu Martha S. Linet Luoping Zhang Guilan Li Lutzen Portengen Jelle Vlaanderen Kim Sungkyoon Richard B. Hayes Songnian Yin Martyn T. Smith Stephen M. Rappaport Nathaniel Rothman |
| author_sort | Roel Vermeulen |
| collection | DOAJ |
| description | Background: Impairment of the hematopoietic system is one of the primary adverse health effects from exposure to benzene. We previously have shown that exposure to benzene at low levels (<1 ppm) affects the blood forming system and that these effects were proportionally stronger at lower versus higher levels of benzene exposure. This observation is potentially explained by saturation of enzymatic systems. Methods: Here we extend these analyses by detailed modeling of the exposure response association of benzene and its major metabolites (i.e. catechol, muconic acid, phenol, and hydroquinone) on peripheral white blood cell (WBC) counts and its major cell-subtypes (i.e. granulocytes, lymphocytes, and monocytes) using two previously published cross-sectional studies among occupationally exposed Chinese workers. Results: Supra-linear exposure response associations were observed between air benzene concentrations (range ∼ 0.1 – 100 ppm) and WBC counts and its cell-subtypes, with a larger than proportional decrease in cell counts at lower than at higher levels of benzene exposure. The hematotoxicity associations were largely similar in shape when the analyses were repeated with benzene urinary metabolites suggesting that enzymatic saturation is not a full explanation of the observed non-linearity with WBC endpoints. Discussion: We hypothesize that the flattening of the exposure response curve especially at higher benzene exposure levels may reflect a response by the bone marrow to maintain hematopoietic homeostasis. Toxicity to the bone marrow and an induced hyper-proliferative response could both contribute to risk of subsequently developing a hematopoietic malignancy. Additional work is needed to explore this hypothesis. |
| first_indexed | 2024-03-13T04:56:58Z |
| format | Article |
| id | doaj.art-adb9d37e5da148e1a862305804e6cc50 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-03-13T04:56:58Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-adb9d37e5da148e1a862305804e6cc502023-06-18T05:00:22ZengElsevierEnvironment International0160-41202023-07-01177108007Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workersRoel Vermeulen0Qing Lan1Qingshan Qu2Martha S. Linet3Luoping Zhang4Guilan Li5Lutzen Portengen6Jelle Vlaanderen7Kim Sungkyoon8Richard B. Hayes9Songnian Yin10Martyn T. Smith11Stephen M. Rappaport12Nathaniel Rothman13Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands; Corresponding author at: Institute for Risk Assessment Sciences (IRAS), Utrecht University, PO Box 80178, 3508 TD, Utrecht, The Netherlands.Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, United StatesNelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, United StatesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, United StatesSchool of Public Health, University of California, Berkeley, CA 94720, United StatesChinese Center for Disease Control and Prevention, Beijing, ChinaInstitute for Risk Assessment Sciences, Utrecht University, Utrecht, the NetherlandsInstitute for Risk Assessment Sciences, Utrecht University, Utrecht, the NetherlandsSchool of Public Health, Seoul National University, Seoul, Republic of KoreaNew York University School of Medicine, New YorkChinese Center for Disease Control and Prevention, Beijing, ChinaSchool of Public Health, University of California, Berkeley, CA 94720, United StatesSchool of Public Health, University of California, Berkeley, CA 94720, United StatesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, United StatesBackground: Impairment of the hematopoietic system is one of the primary adverse health effects from exposure to benzene. We previously have shown that exposure to benzene at low levels (<1 ppm) affects the blood forming system and that these effects were proportionally stronger at lower versus higher levels of benzene exposure. This observation is potentially explained by saturation of enzymatic systems. Methods: Here we extend these analyses by detailed modeling of the exposure response association of benzene and its major metabolites (i.e. catechol, muconic acid, phenol, and hydroquinone) on peripheral white blood cell (WBC) counts and its major cell-subtypes (i.e. granulocytes, lymphocytes, and monocytes) using two previously published cross-sectional studies among occupationally exposed Chinese workers. Results: Supra-linear exposure response associations were observed between air benzene concentrations (range ∼ 0.1 – 100 ppm) and WBC counts and its cell-subtypes, with a larger than proportional decrease in cell counts at lower than at higher levels of benzene exposure. The hematotoxicity associations were largely similar in shape when the analyses were repeated with benzene urinary metabolites suggesting that enzymatic saturation is not a full explanation of the observed non-linearity with WBC endpoints. Discussion: We hypothesize that the flattening of the exposure response curve especially at higher benzene exposure levels may reflect a response by the bone marrow to maintain hematopoietic homeostasis. Toxicity to the bone marrow and an induced hyper-proliferative response could both contribute to risk of subsequently developing a hematopoietic malignancy. Additional work is needed to explore this hypothesis.http://www.sciencedirect.com/science/article/pii/S0160412023002805BenzeneHematotoxicityComplete blood cell countExposure–responseQuantile-regression |
| spellingShingle | Roel Vermeulen Qing Lan Qingshan Qu Martha S. Linet Luoping Zhang Guilan Li Lutzen Portengen Jelle Vlaanderen Kim Sungkyoon Richard B. Hayes Songnian Yin Martyn T. Smith Stephen M. Rappaport Nathaniel Rothman Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers Environment International Benzene Hematotoxicity Complete blood cell count Exposure–response Quantile-regression |
| title | Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers |
| title_full | Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers |
| title_fullStr | Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers |
| title_full_unstemmed | Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers |
| title_short | Nonlinear low dose hematotoxicity of benzene; a pooled analyses of two studies among Chinese exposed workers |
| title_sort | nonlinear low dose hematotoxicity of benzene a pooled analyses of two studies among chinese exposed workers |
| topic | Benzene Hematotoxicity Complete blood cell count Exposure–response Quantile-regression |
| url | http://www.sciencedirect.com/science/article/pii/S0160412023002805 |
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