Winter 2025

Health Effects of Exposure to Benzene

By Robyn Prueitt, Ph.D., DABT

Benzene is a liquid at ambient temperatures but it evaporates very quickly, and most exposures occur by inhalation of benzene in the air.  After exposure occurs and benzene enters the body, it is metabolized, or transformed, into several different metabolites that are highly reactive and can move throughout the body.  This metabolism has been shown to be necessary to produce the toxicity associated with benzene exposure, but there is currently no scientific consensus as to which metabolite or metabolites of benzene produce its toxic effects (Baan et al., 2019).

[S]ufficient exposure to benzene has been known to cause bone marrow toxicity in humans since the nineteenth century.”

The health effects associated with inhalation of benzene have been studied widely in human populations and laboratory animals, and these studies indicate that the primary targets of benzene toxicity are the blood and bone marrow.  In fact, sufficient exposure to benzene has been known to cause bone marrow toxicity in humans since the nineteenth century (Baan et al., 2019).  Studies of workers with long-term occupational exposure to benzene at concentrations that exceed regulated workplace limits have reported an increase in the incidence of aplastic anemia, a condition in which the bone marrow is damaged and cannot produce enough normal blood cells (ATSDR, 2007).  The most sensitive indicator of benzene toxicity (i.e., the health effect that occurs at the lowest exposure concentration) is a lower-than-normal number of circulating white blood cells, particularly the subset of white blood cells known as lymphocytes, which have important functions in the body’s immune response to infections (ATSDR, 2007).

In addition, benzene exposure has been associated with the development of adult acute myeloid leukemia (AML).  AML is a type of blood cancer that can progress rapidly.  It occurs when the stem cells in the bone marrow that are responsible for producing healthy blood cells instead produce abnormal blood cells that multiply uncontrollably, causing the bone marrow to stop making healthy blood cells (see Figure).  Benzene has been recognized as a cause of AML for decades, based on reports of an increased incidence of AML in studies of workers with long-term exposure to high concentrations of benzene in workplace air (Baan et al., 2019).  Associations between benzene exposure and other types of leukemias and blood cancers have not been reported consistently across studies (IARC, 2018).  In addition, benzene exposure has not been associated consistently with any type of cancer in children (IARC, 2018).  While some carcinogenic substances cause cancer by directly causing mutations in DNA, such that any level of exposure can cause a mutation and increase cancer risk, benzene does not directly mutate DNA.  Thus, there is growing evidence that benzene should be considered as having a threshold exposure level below which there is no increased cancer risk (North et al., 2020).

Benzene Exposure Is Associated with Acute Myeloid Leukemia

The studies of benzene workers have several methodological limitations that make it difficult to fully understand what benzene concentrations are necessary to cause its harmful effects (ATSDR, 2007; IARC, 2018), but studies of long-term inhalation benzene exposure in laboratory animals provide support for the findings in human studies.  Chronic benzene exposure at sufficient concentrations (at least 100 parts per million [ppm] benzene) in laboratory rodents has been shown to reduce the production of blood cells by the bone marrow, reduce the number of circulating lymphocytes, and cause several types of cancer, including blood cancers (ATSDR, 2007).  In addition to its long-term effects on the blood and bone marrow, exposure to very high concentrations of benzene in air for a short period of time has been reported to cause reversible effects on the central nervous system, such as drowsiness, dizziness, rapid heart rate, headaches, and confusion, as well as skin irritation, eye irritation, and shortness of breath (ATSDR, 2007).  Further, most studies on the health effects of benzene exposure by routes other than inhalation have been conducted in laboratory animals.  For example, these studies have reported effects on the nervous system and blood cell production, as well as various types of cancers, when benzene was ingested, and skin irritation effects, but no development of skin cancers, when benzene was applied directly to the skin (ATSDR, 2007).

Overall, long-term exposure to concentrations of benzene that exceed workplace limits is known to cause adverse effects on the bone marrow and the production of blood cells, so it is important to limit such exposures in workplaces that make or use benzene.  Although benzene is also present in the ambient air and in certain products, exposures to the public from these sources, even if long term, are not expected to be sufficient to cause the health effects observed in studies with high occupational exposures.