Benchmark dose estimation for benzene-exposed workers in China: Based on quantitative and multi-endpoint genotoxicity assessments

Yiyi Cao; Tongshuai Wang; Jing Xi; Wei Tian; Weiying Liu; Yuan Sun; Wuzhong Liu; Xinyue You; Anqi Li; Guanghui Zhang; XinYu Zhang; Zhao-Lin Xia; Yang Luan

doi:10.1016/j.envpol.2023.121765

Benchmark dose estimation for benzene-exposed workers in China: Based on quantitative and multi-endpoint genotoxicity assessments

Environ Pollut. 2023 Aug 1:330:121765. doi: 10.1016/j.envpol.2023.121765. Epub 2023 May 2.

Authors

Yiyi Cao¹, Tongshuai Wang², Jing Xi¹, Wei Tian³, Weiying Liu¹, Yuan Sun⁴, Wuzhong Liu⁴, Xinyue You¹, Anqi Li⁵, Guanghui Zhang⁶, XinYu Zhang¹, Zhao-Lin Xia⁷, Yang Luan⁸

Affiliations

¹ School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
² Department of Occupational Health & Toxicology, School of Public Health, Fudan University, Shanghai, 200030, China; Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 200120, Shanghai, China.
³ School of Public Health, Xinjiang Medical University, Urumqi, 830000, China.
⁴ Shanghai Institute of Occupational Disease for Chemical Industry (Shanghai Institute of Occupational Safety & Health), Shanghai, 200000, China.
⁵ Department of Occupational Health & Toxicology, School of Public Health, Fudan University, Shanghai, 200030, China.
⁶ Department of Environmental Health, College of Preventive Medicine, Army Medical University, Chongqing, 400038, China.
⁷ Department of Occupational Health & Toxicology, School of Public Health, Fudan University, Shanghai, 200030, China; School of Public Health, Xinjiang Medical University, Urumqi, 830000, China.
⁸ School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: yluan@sjtu.edu.cn.

PMID: 37142205
DOI: 10.1016/j.envpol.2023.121765

Abstract

Based on previous exposure studies, benzene (BZ) has been classified as a human carcinogen and occupational exposure limit (OELs) for BZ has been set to be about 1 ppm around the world. However, health hazards have still been reported with exposure below the OEL. Thus, the OEL needs to be updated to reduce health risk. The overall aim of our study was therefore to generate new OEL for BZ via a benchmark dose (BMD) approach and based on quantitative and multi-endpoint genotoxicity assessments. Genotoxicities were determined using the novel human PIG-A gene mutation assay, the micronucleus (MN) test and the COMET assay in benzene-exposed workers. Among the 104 workers with below current OELs, they exhibited significantly higher PIG-A mutant frequencies (MFs) (15.96 ± 14.41 × 10^-6) and MN frequencies (11.55 ± 6.83‰) than those among the controls (PIG-A MFs: 5.46 ± 4.56 × 10^-6, MN frequencies: 4.51 ± 1.58 ‰), but no difference in the COMET assay. A significant association was also observed between BZ exposure doses and PIG-A MFs and MN frequencies (P < 0.001). Our results indicate that health hazards were induced among workers with below OEL exposures. Based on results from the PIG-A and MN assays, the lower confidence limit of the BMD (BMDL) were calculated to be 8.71 mg/m³-year and 0.44 mg/m³-year, respectively. Based on these calculations, the OEL for BZ was determined to be lower than 0.07 ppm. This value can be considered by regulatory agencies to set new exposure limits and to better protect workers.

Keywords: Benchmark dose; Benzene; Biomarkers; Genotoxicity; Occupational exposure limits.

MeSH terms

Benchmarking
Benzene* / toxicity
China
DNA Damage
Humans
Micronucleus Tests
Occupational Exposure* / analysis

Substances

Benzene