Occupational Exposure to Benzene and Chromosomal Structural Aberrations in the Sperm of Chinese Men
Marchetti, Francesco, Eskenazi, Brenda, Weldon, Rosana H., Li, Guilan, Zhang, Luoping, Rappaport, Stephen M., Schmid, Thomas E., Xing, Caihong, Kurtovich, Elaine, Wyrobek, Andrew J., Environmental Health Perspectives
BACKGROUND: Benzene is an industrial chemical that causes blood disorders, including acute myeloid leukemia. We previously reported that occupational exposures near the U.S. Occupational Safety and Health Administration permissible exposure limit (8 hr) of 1 ppm was associated with sperm aneuploidy
OBJECTIVE: We investigated whether occupational exposures near 1 ppm increase the incidence of sperm carrying structural chromosomal aberrations.
METHODS: We applied a sperm fluorescence in situ hybridization assay to measure frequencies of sperm carrying partial chromosomal duplications or deletions of Icen or lp36.3 or breaks within lcen-1q12 among 30 benzene-exposed and 11 unexposed workers in Tianjin, China, as part of the China Benzene and Sperm Study (C-BASS). Exposed workers were categorized into low-, moderate-, and high-exposure groups based on urinary benzene (medians: 2.9, 11.0, and 110.6[micro]g/L, respectively). Median air benzene concentrations in the three exposure groups were 1.2, 3.7, and 8.4 ppm, respectively.
RESULTS: Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for all structural aberrations combined were 1.42 (95% CI: 1.10, 1.83), 1.44 (95% CI: 1.12, 1.85), and 1.75 (95% CI: 1.36, 2.24) and for deletion of lp36.3 alone were 4.31 (95% CI: 1.18, 15.78), 6.02 (95% CI: 1.69, 21.39), and 7.88 (95% CI: 2.21, 28.05) for men with low, moderate, and high exposures respectively, compared with unexposed men. Chromosome breaks were significantly increased in the high-exposure group [IRR 1.49 (95% CI: 1.10, 2.02)].
CONCLUSIONS: Occupational exposures to benzene were associated with increased incidence of chromosomally defective sperm, raising concerns for worker infertility and spontaneous abortions as well as mental retardation and inherited defects in their children. Our sperm findings point to benzene as a possible risk factor for de novo lp36 deletion syndrome. Because chromosomal aberrations in sperm can arise from defective stem cells/spermatogonia, our findings raise concerns that occupational exposure to benzene may have persistent reproductive effects in formerly exposed workers.
KEY WORDS: benzene, chromosome 1, germ cells, sperm fluorescence in situ hybridization, structural aberrations. Environ Health Perspect 120:229-234 (2012). http://dx.doi.org/10.1289/ehp.1103921 [Online 15 November 2011]
Benzene is an important industrial chemical with Greater than 2 billion pounds produced every year in the United States. Low-level exposures (Less than 5 ppb) to benzene, widespread in the U.S. population, are primarily due to smoking, gasoline fumes, and vehicle emissions (Hricko 1994). Early epidemiological cohort studies found that benzene is associated with an increased risk of leukemia at high levels (around 10 ppm average or 40 ppm-years) (Hayes et aI. 1997; Yin et al. 1996, l987a, 1987b), whereas more recent studies found excess leukemia risk associated with levels of exposure as low as 0.8-1.6 ppm or 2-4 ppm-years of cumulative exposure (Glass et al. 2003, 2004; Hayes et al. 2001). Benzene is hematotoxic, and in a large study of more than 400 workers, almost all blood cell counts were significantly decreased, even in individuals exposed to Less than 1 ppm benzene [mean [+ or -] SD of exposed individuals 0.57 [+ or -] 0.24 ppm, and mean of unexposed individuals [less than or equal to] 0.04 ppm (Lan et al. 2004)]. Therefore, benzene is highly regulated with the U.S. permissible exposure limit (PEL; 8-hr time-weighted average) set at 1 ppm by the Occupational Safety and Health Administration (OSHA 1987). Although significant international progress has been seen in reducing occupational exposure to benzene, workers in some countries still experience levels of benzene well above the U.S. PEL (Liang et al. 2005).
Specific chromosomal aneuploidies and aberrations implicated in leukemia have been detected in the blood cells of benzene-related leukemia patients as well as in healthy benzene-exposed workers, suggesting that these abnormalities precede and may he a potential mechanism underlying benzene-induced leukemia (Zhang et al. …