Benzene exposure linked to sperm abnormalities that cause birth defects.

Feb 16, 2010

Xing C, F Marchetti, G Li, RH Weldon, E Kurtovich, S Young, TE Schmid, L Zhang, S Rappaport, S Waidyanatha, AJ Wyrobek and B Eskenazi. 2010. Benzene exposure near the U.S. permissible limit is associated with sperm aneuploidy. Environmental Health Perspectives doi: 10.1289/ehp.0901531.




2010-0215sperm
Andy Wyrobek/Lawrence Berkeley National Laboratory
 Men exposed to benzene at levels close to the U.S. permissible limit are more likely to have an abnormal number of chromosomes in their sperm, researchers report in the journal Environmental Health Perspectives.
 
Some sperm can develop with either too many or too few chromosomes. Known as aneuploidy, this can adversely impact fertility and fetal development. Aneuploidy (in either the sperm or the egg) is the largest known cause of miscarriages in people.
 
This study of male factory workers in China has linked benzene exposure to aneuploidy in the men’s sperm.
 
  

Context

Benzene is a common industrial chemical that can be found in gasoline, paints, marking pens, rubber products and solvents. It is also released in cigarette smoke and vehicle exhaust.

Benzene has been associated with increased risk of cancer, particularly leukemia and lymphoma in adults (IARC 1982) and childhood leukemia. It is also linked to developmental, immune, neurological, reproductive and respiratory effects.

Exposure occurs indoors and out. Because benzene is extremely volatile, exposure generally occurs by breathing it in, but sometimes it is found in drinking water.

Indoor air sources include emissions from cars in attached garages, household surface coatings, consumer products, wood smoke and burning candles.

Urban areas typically have the highest outdoor concentrations of benzene because of traffic emissions. However, reductions in the amount of benzene allowed in gasoline have led to declines in annual average outdoor air concentrations (U.S. EPA 2003).

Smoking, pumping gas or spending time in a vehicle increases personal exposure to the chemical. Smokers are exposed to about five to 10 times more benzene than non-smokers. One study showed more than half of the total U.S. exposure was from smoking or exposure to tobacco smoke (Wallace 1989).

All people are exposed to low levels, but some occupations have higher exposures. The U.S. Occupational Safety and Health Administration requires that workers not exceed 1 part per million (ppm) of benzene exposure in an 8-hour work day. Many other countries have higher limits.

Studies are finding health effects at exposures lower than 1 ppm, including reduced white blood cell and platelet counts and increased frequency of sperm aneuploidy.

What did they do?

Researchers enrolled 66 men working in factories in Tianjin, China. Thirty-three men were recruited from factories that used benzene-containing adhesives to produce shoes, paper bags and sandpaper. These men were considered exposed to benzene. The researchers also enrolled 33 men who worked in a meat packing plant and an ice cream factory and were not exposed to benzene.

To confirm benzene exposure, men wore personal air monitors to measure benzene levels in the air at their workplace. Levels of benzene and benzene metabolites were also measured in the men’s urine. Based on their levels of urinary metabolites of benzene, the men were divided into three groups for comparison of sperm aneuploidy: 33 unexposed, 17 low-exposed and 16 high-exposed.

A semen sample was collected from each man. The researchers then applied colored fluorescent tags to chromosome 21 and to the X and Y chromosomes. The sperm were examined under a microscope and the number of colored chromosomes were visually identified and counted. For each man, 10,000 sperm were analyzed to determine the number of sperm cells with aneuploidy.

What did they find?

The researchers found that as men’s benzene exposure becomes higher, the number of sperm they produce with an extra sex chromosome also increases.

Compared to men with no benzene exposure, men with low exposure to benzene are twice as likely to have some sperm with two X chromosomes. Men with high exposure are almost three times as likely. Men with high exposure are also more likely to have sperm with two Y chromosomes.

What does it mean?

Men exposed to benzene at work have a two or three times higher risk for having abnormal numbers of chromosomes in their sperm than men who have not been exposed to the chemical.  These associations were seen at benzene levels lower than previously reported.

In this study, “low exposure” meant levels of benzene that are similar to the maximum level that the U.S. government deems safe for occupational exposure. Although other studies have found associations of high benzene exposure with sperm aneuploidy, this is the first study to find associations with benzene levels below the U.S. permissible limit.

The study raises the question of whether the U.S. permissible limit for occupational benzene exposure is sufficient to protect men from reproductive harm.

Chromosomes contain DNA – the hereditary material that guides how plants and animals develop, grow and maintain themselves. Healthy human sperm have 23 chromosomes, including one sex chromosome (either an X or a Y). The other 23 in the egg includes one X chromosome. When the sperm fertilizes the egg, the chromosomes pair and become a set of 46.

Cells that have too few or too many chromosomes are called aneuploid, and sex cells are particularly vulnerable to the condition. Many men have some sperm with either two Xs, two Ys or an XY. If one of these sperm fertilize an egg, the resulting child may suffer from chromosomal disorders, such as Klinefelter Sydrome (X-X-Y).

Men in the low exposure group of this study had daily levels of approximately 1 parts per million and men in the high exposure group had daily levels closer to 8 ppm. These levels are high, even for an occupational setting. It is unlikely that the average American would be exposed to levels as high as even the low exposure group in this study.

Although the general public isn’t likely to have benzene levels as high as those seen in this study, it is unclear what effects lower levels of exposure could be having. This study indicates that reducing benzene exposure might reduce reproductive risks in men.

Resources

Ambient concentrations of benzene. 2008. US Environmental Protection Agency. (PDF)

Benzene. 1982. In "IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans: Some Industrial Chemicals and Dyestuffs." Lyon, France: International Agency for Research on Cancer, pp. 93-148.

Benzene Toxicity: Physiologic Effects. 2000. Case Studies in Environmental Medicine. Agency for Toxic Substances and Disease Registry.

Facts about benzene. 2005. Centers for Disease Control and Prevention.

U.S. Environmental Protection Agency. National Air Quality and Emissions Trends Report, Special Studies Edition. 2003. Publication No. EPA 454/R-03-005, pp. 64.

Wallace, LA. 1989. The exposure of the general population to benzene. Cell and Biological Toxicology. 5(3):297-314.

 

 

 

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