Benzene is a human carcinogen widely used in the United States, ranked in the top 20 chemicals for production volume. It is the primary starting material for chemicals used to make plastics, resins, synthetic fibers, dyes, detergents, drugs, and pesticides. Benzene is also a component of crude oil, gasoline, and cigarette smoke.

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Benzene is strongly associated with blood and immune system disorders, including anemia, leukemia and lymphoma.

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The general population is exposed to benzene mainly through breathing of fuel emission exhaust, tobacco smoking and second-hand smoking, and through breathing vapors of household items like paints, adhesives, marking pens, rubber products and tapes.

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Common genetic variations in metabolic genes can alter individual susceptibility to benzene toxicity.

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Routes of exposure

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Environmental exposure to benzene is quite variable because it is influenced by several factors like individual lifestyles, weather conditions, living environments and geographical location. The main environmental sources of benzene exposure are related to fuel emission exhaust from motor vehicles and evaporation losses from handling, distribution and storage of fuels. Another major source of environmental benzene exposure is tobacco smoking for both mainstream and second-hand smokers. It has been found that smokers receive 90% of their total benzene exposure from smoking and that benzene concentration in the breathing air of smokers can be 10–20-times higher than in nonsmokers. Other sources may also contribute to the cumulative benzene indoor concentration. Household items like paints, adhesives, marking pens, rubber products and tapes emit benzene vapors.

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Health effects of benzene

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The solvent acts like a pro-carcinogen that damages the DNA. In a recent re-evaluation of the carcinogenicity of benzene, the International Agency for Research on Cancer (IARC, 2012) has concluded that there is sufficient evidence in humans for a causal role in inducing leukemia, lymphoma and myeloma.​

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During metabolism of benzene, electrophilic metabolites are produced together with highly reactive oxygen species (ROS). These compounds induce a condition of oxidative stress onto lipids, proteins and nucleic acids. The oxidation of such biological cell components results in cell damage, DNA lesions and strand breaks, favoring mutagenesis and chromosomal aberrations as well as alteration of RNA transcription and protein translation process. As a result, the benzene uptake by bone marrow affects the stem cell differentiation and proliferation, leading to malignant transformation of hematopoietic blood cells. B-cell and T-cell proliferation is also reduced by benzene, altering the immune system response.

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Occupational exposure to benzene is associated with a higher risk of toxic and carcinogenic effects, in particular on the lympho-haematopoietic system: the solvent may induce bone marrow suppression, causing anemia, abnormal blood count and leukemia. In China, where benzene has been used extensively resulting in very high air concentrations, a haematotoxic syndrome called chronic benzene poisoning has been even recognized by the Ministry of Health.

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Both toxic and carcinogenic effects have been demonstrated recently also for exposures in the ppb (parts per billion) range, i.e. lower than the 8 h occupational exposure limit (1 part in a million) recommended by both the European Scientific Committee for Occupational Exposure Limit and the U.S. Occupational Safety and Health Administration (OSHA). A supralinear (“more than expected”) relationships between low-dose exposure and metabolism of benzene has been discovered. Low dose exposure may be as bad as being exposed to a dose 1000 times larger.

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The International Agency for Research on Cancer (IARC) is part of the World Health Organization (WHO). One of its goals is to identify causes of cancer. IARC classifies benzene as “carcinogenic to humans,” based on sufficient evidence that benzene causes acute myeloid leukemia (AML). IARC also notes that benzene exposure has been linked with acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin lymphoma.

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The National Toxicology Program (NTP) is formed from parts of several different US government agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA). The NTP has classified benzene as “known to be a human carcinogen.”

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The US Environmental Protection Agency (EPA) maintains the Integrated Risk Information System (IRIS), an electronic database that contains information on human health effects from exposure to various substances in the environment. The EPA classifies benzene as a known human carcinogen.

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Epidemiology

 

​In the United States, workers are exposed to potentially high levels of benzene in the chemical industry, in petroleum refineries, in oil pipelines, on ships and tankers, in auto repair shops, and in bus garages. Occupational exposures in the developing world are sometimes very high because of the continuing presence of benzene in industrial solvents and glues.

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The general population is exposed to benzene mainly through breathing of fuel emission exhaust from motor vehicles, tobacco smoking and second-hand smoking, and through breathing vapors of household items like paints, adhesives, marking pens, rubber products and tapes.

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Metabolism

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Inhaled benzene is readily absorbed into the blood, taking 40 to 70% of airborne dose by passive diffusion through the lung capillary membranes. Benzene undergoes biotransformation within the liver but can be metabolized also in the lung and bone marrow.

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Biotransformation of benzene generates electrophilic metabolites as well as reactive oxygen species (ROS) as biotransformation byproducts. Both these categories of electrophilic species may modify, upon covalent binding to nucleophilic moieties, cell macromolecules (DNA, RNA, proteins, lipids).

 

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Genetic sensitivity to benzene

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Many studies referred high variability in the levels of benzene biomarkers in humans, suggesting the involvement of polymorphic metabolic genes in the individual susceptibility to benzene toxicity.

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The NQO1 enzyme acts by decreasing the formation of free radicals (semiquinones), hence protecting cells against the adverse effects of quinones and their derivatives. The mutant NQO1*2 protein is very unstable, and is rapidly degraded, making it virtually undetectable in humans carrying two copies of this variant (NQO1*2/*2 genotype).

 

The NQO1*2 is the more prominent polymorphism associated with benzene toxicity, in terms of both frequency and consequences of the genetic variation. A higher risk of chronic benzene poisoning was observed among heavily exposed workers carrying the homozygous NQO1 variant genotype. Deleterious effects was also found in workers exposed to low levels of benzene, such as taxi drivers and gasoline station attendants. The NQO1*2 polymorphism prevalence was found higher in families whose children are affected by acute lymphocytic leukemia.

 

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How to reduce the risk from exposure to benzene

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Benzene exposure can be reduced by limiting contact with its sources. People are exposed to benzene from both active and passive second hand smoke. Average smokers take in about 10 times more benzene than nonsmokers each day. Families are encouraged not to smoke in their house, in enclosed environments, or near their children.

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Benzene is a major component of gasoline and used in many manufacturing processes. Increased levels of benzene can be found at fueling stations, and in air emissions from manufacturing plants and hazardous waste sites. Living near gasoline fueling stations or hazardous waste sites may increase exposure to benzene. People are advised not to have their families play near fueling stations, manufacturing plants, or hazardous waste sites. Try to limit gasoline fumes by pumping gas carefully and using gas stations with vapor recovery systems that capture the fumes. Avoid skin contact with gasoline.

 

When possible, limiting the time you spend near idling car engines can help lower your exposure to exhaust fumes, which contain benzene (as well as other potentially harmful chemicals).

 

Limit or avoid exposure to fumes from solvents, paints, and art supplies, especially in unventilated spaces.

 

If you are exposed at your workplace, talk to your employer about limiting your exposure through process changes (such as replacing the benzene with another solvent or enclosing the benzene source) or by using personal protective equipment. If needed, the Occupational Safety & Health Administration (OSHA) can provide more information or make an inspection.

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