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

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 x 10-6) and MN frequencies (11.55 +/- 6.83%o) than those among the controls (PIG-A MFs: 5.46 +/- 4.56 x 10-6, MN frequencies: 4.51 +/- 1.58 %o), 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 deter-mined 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.

Automated summary

Based on previous exposure studies, benzene (BZ) has been classified as a human carcinogen and the current occupational exposure limit (OEL) of 1 ppm may not sufficiently protect against health hazards. This study used genotoxicity assessments to determine the hazards of benzene exposure below the OEL. The results indicated that lower OELs are necessary to better protect workers, with a proposed value of less than 0.07 ppm.