Report on Carcinogens, Fifteenth Edition For Table of Contents, see home page: http://ntp.niehs.nih.

gov/go/roc

Benzene Properties
Benzene is the primary aromatic compound. It exists at room tem-
CAS No. 71-43-2 perature as a clear, colorless-to-yellow liquid with an aromatic odor.
Known to be a human carcinogen It is only slightly soluble in water, but it is miscible with alcohol, ether,
chloroform, carbon disulfide, acetone, oils, carbon tetrachloride, gla-
First listed in the First Annual Report on Carcinogens (1980)
cial acetic acid, and most other organic solvents. Benzene is highly
flammable (Akron 2009). Physical and chemical properties of ben-
zene are listed in the following table.

Property Information
Carcinogenicity
Molecular weight 78.1
Benzene is known to be a human carcinogen based on sufficient evi- Specific gravity 0.8787 at 15°C/4°C
dence of carcinogenicity from studies in humans. Melting point 5.5°C
Boiling point 80.1°C
Cancer Studies in Humans Log Kow 2.13
Case reports and case series have reported leukemia (mostly acute Water solubility 1.79 g/L at 25°C
myelogenous leukemia, also known as acute myeloid or myelocytic Vapor pressure 94.8 mm Hg at 25°C
Vapor density relative to air 2.8
leukemia) in individuals exposed to benzene. The strongest epide-
miological evidence that benzene causes cancer is from several co- Source: HSDB 2009.

hort studies in various industries and geographical locations, which

found that occupational exposure to benzene increased the risk of Use
mortality from leukemia (mainly acute myelogenous leukemia). Case- Benzene is used primarily as a solvent in the chemical and pharma-
control studies also reported that exposure to benzene increased the ceutical industries, as a starting material and intermediate in the syn-
risk of leukemia, but the usefulness of these studies was limited by thesis of numerous chemicals, and in gasoline. As a raw material, it is
poorly defined exposures and mixed exposure patterns (IARC 1974, used in the synthesis of ethylbenzene (used to produce styrene) (53%),
1982, 1987). cumene (used to produce phenol and acetone) (22%), cyclohexane
Since benzene was reviewed for listing in the First Annual Report (12%), nitrobenzene (used to produce aniline and other chemicals)
on Carcinogens, numerous epidemiological studies of benzene expo- (5%), detergent alkylate (linear alkylbenzene sulfonates) (3%), and
sure and cancer have been published. The International Agency for chlorobenzenes and other products (5%). Benzene is used as an ad-
Research on Cancer (IARC) evaluated benzene in 2012 and concluded ditive in gasoline, but it also is present naturally in gasoline, because
that there was sufficient evidence for the carcinogenicity of benzene it occurs naturally in crude oil and is a by-product of oil-refining pro-
in humans, based on a causal relationship with myeloid leukemia/ cesses. The percentage of benzene in unleaded gasoline is approxi-
acute nonlymphocytic leukemia (IARC 2012). IARC also concluded mately 1% to 2% by volume (ATSDR 1997, HSDB 2009).
that there was limited evidence of carcinogenicity based on a pos-
itive association between exposure to benzene and acute lympho- Production
cytic leukemia, chronic lymphocytic leukemia, multiple myeloma, Benzene has been produced commercially from coal since 1849 and
and non-Hodgkin lymphoma. from petroleum since 1941. Since 1959, the major U.S. source of
benzene has been petroleum (IARC 1989). In 2009, 59 U.S. manu-
Cancer Studies in Experimental Animals facturers (SRI 2009) and 24 U.S. suppliers of benzene were identified
Studies in experimental animals, including many published after (ChemSources 2009). In 2015, the U.S. Environmental Protection
benzene was listed in the First Annual Report on Carcinogens, have Agency (EPA) estimated that combined production and imports of
demonstrated that benzene causes cancer at numerous tissue sites in benzene were in the range of 10 to 20 billion pounds, similar to the
rodents. Oral exposure to benzene caused cancer of the Zymbal gland 12.0 to 17.8 billion pounds reported for production only from 1990
(carcinoma) in rats and mice of both sexes, cancer of the oral cav- to 2000 (CEN 2003). In 2017, U.S. imports of benzene were substan-
ity (squamous-cell carcinoma) in rats of both sexes, malignant lym- tially higher than exports (as shown in the following table).
phoma and lung cancer (alveolar/bronchiolar carcinoma) in mice of
both sexes, skin cancer (squamous-cell carcinoma) in male rats, be- Category Year Quantity (lb)
nign tumors of the Harderian gland (adenoma) and cancer of the pre- Production + imports a
2015 10 billion to 20 billion
putial gland (carcinoma) in male mice, and benign ovarian tumors U.S. importsb 2017 6.5 billion
and cancer of the mammary gland (carcinoma and carcinosarcoma) U.S. exportsb 2017 372.5 million
in female mice (NTP 1986, Huff et al. 1989). Inhalation exposure to Sources: aEPA 2016. bUSITC 2018 (imports reported as “benzene of a purity of 95% or
benzene caused tumors at many tissue sites in rats and a tendency more by weight”).

towards induction of lymphoid tumors in mice. Benzene adminis-

tered by intraperitoneal injection caused benign lung tumors in male Exposure
mice (IARC 1982, 1987). Dermal application of benzene caused be- People are exposed to benzene in the workplace and in their everyday
nign skin tumors in transgenic mice carrying the v‑Ha‑ras onco- lives. Occupational exposure may occur during production of ben-
gene, which increases their susceptibility to carcinogens (Blanchard zene or use of substances containing it. In the vulcanization step of
et al. 1998, Spalding et al. 1999, French and Saulnier 2000). In het- tire manufacturing, benzene was measured at concentrations of up to
erozygous p53‑deficient mice (with only one functional copy of the 27.2 mg/m3, resulting in an estimated daily intake of 0.0045 mg/kg of
p53 tumor-suppressor gene), benzene administered by stomach tube body weight for workers (Durmusoglu 2007). The National Occupa-
caused cancer (sarcoma) of head and neck, thoracic cavity, and sub- tional Health Survey (conducted from 1972 to 1974) estimated that
cutaneous tissue (French et al. 2001, Hulla et al. 2001). 147,600 U.S. workers potentially were exposed to benzene (NIOSH

National Toxicology Program, Department of Health and Human Services For definitions of technical terms, see the Glossary.
Report on Carcinogens, Fifteenth Edition For definitions of technical terms, see the Glossary.

1976), and the National Occupational Exposure Survey (conducted Regulations

from 1981 to 1983) estimated that about 272,000 workers, including
Coast Guard, Dept. of Homeland Security
143,000 women, potentially were exposed to benzene (NIOSH 1990).
Comprehensive regulations have been established for safe transport of benzene on ships and barges.
Evidence that the U.S. general population is exposed to benzene
Consumer Product Safety Commission (CPSC)
comes from the 2013–2014 National Health and Nutrition Examina-
Products containing 5% or more by weight of benzene are considered hazardous and require special
tion Survey (NHANES), which found that the 95th-percentile con-
labeling.
centration of benzene in whole blood was 0.285 ng/mL (0.285 µg/L), Solvents for paints or other surface-coating materials containing 10% or more by weight of benzene
based on a sample of 3,094 individuals of all ages, both genders, and require special packaging.
all race and ethnicity groups (CDC 2018a). The primary route of hu- Department of Transportation (DOT)
man exposure to benzene is inhalation of ambient air. The general Benzene is considered a hazardous material, and special requirements have been set for marking,
population can also be exposed to benzene by inhaling air containing labeling, and transporting this material.
tobacco smoke, drinking contaminated water, or eating contaminated Environmental Protection Agency (EPA)
food. About half of the total national exposure to benzene comes from Clean Air Act
cigarette smoke. In the NHANES study, benzene levels in blood were Comprehensive regulations have been developed to control benzene levels in gasoline and benzene
much higher in smokers (95th percentile = 0.500 ng/mL [0.500 µg/L], emissions from motor vehicles.
915 samples) than in nonsmokers (0.081 ng/mL [0.081 µg/L], 2,049 Mobile Source Air Toxics: Beginning in 2011, refiners must meet an annual average gasoline benzene
content standard of 0.62% by volume (vol%) on all gasoline; by 2012, a maximum benzene
samples) (CDC 2018b). In a study of benzene levels in homes, the
content of 1.3 vol% may not be exceeded.
median level was 2.2 ppb (7 μg/m3) in 185 homes without smokers National Emission Standards for Hazardous Air Pollutants: Listed as a hazardous air pollutant.
and 3.3 ppb (10.5 μg/m3) in 343 homes with one or more smokers. New Source Performance Standards: Manufacture is subject to certain provisions for the control of
Amounts of benzene measured per cigarette ranged from 5.9 to 75 μg volatile organic compound emissions.
in mainstream smoke and from 345 to 653 μg in sidestream smoke. Urban Air Toxics Strategy: Identified as one of 33 hazardous air pollutants that present the greatest
threat to public health in urban areas.
Benzene has also been found in some consumer products, includ-
Clean Water Act
ing hand sanitizers and sun-care products. In 2021, an independent
Designated a hazardous substance.
testing laboratory reported benzene contamination at levels rang-
Effluent Guidelines: Listed as a toxic pollutant.
ing from 0.1 to 16.1 ppm in 44 (17%) of 260 unique batches of liquid Water Quality Criteria: Based on fish or shellfish and water consumption = 0.58 to 2.1 μg/L; based on
and non-liquid hand sanitizers and at levels ranging from < 0.1 to fish or shellfish consumption only = 16 to 58 μg/L.
6.26 ppm in 78 (27%) of 294 unique batches of sunscreen and after- Comprehensive Environmental Response, Compensation, and Liability Act
sun products (sprays, gels, and lotions with chemical- and mineral- Reportable quantity (RQ) = 10 lb.
based formulations) (Valisure 2021a,b). Benzene has been detected Emergency Planning and Community Right-To-Know Act
in fruits, vegetables, nuts, dairy products, eggs, and fish. In a 1992 Toxics Release Inventory: Listed substance subject to reporting requirements.
survey of more than 50 foods, benzene concentrations in foods con- Resource Conservation and Recovery Act
taining both benzoate and ascorbate food additives ranged from less Characteristic Hazardous Waste: Toxicity characteristic leaching procedure (TCLP) threshold = 0.5 mg/L.
than 1 to 38 ppb (< 3 to 120 μg/m3) (ATSDR 1997). Listed Hazardous Waste: Waste codes for which the listing is based wholly or partly on the presence of
Benzene is present in the atmosphere both from natural sources, benzene = U019, F005, F024, F025, F037, F038, K085, K104, K105, K141, K142, K143, K144, K145,
which include forest fires and oil seeps, and from industrial sources, K147, K151, K159, K169, K171, K172.
Listed as a hazardous constituent of waste.
which include automobile exhaust, industrial emissions, and fuel
evaporation from gasoline filling stations. Benzene has been mea- Safe Drinking Water Act
sured in outdoor air at various U.S. locations at concentrations rang- Maximum contaminant level (MCL) = 0.005 mg/L.
ing from 0.02 ppb (0.06 μg/m3) in a rural area to 112 ppb (356 μg/m3) in Food and Drug Administration (FDA, an HHS agency)
an urban area. The maximum 24-hour average concentrations of ben- Maximum permissible level in bottled water = 0.005 mg/L.
Residues of benzene used as a solvent in producing modified hop extract shall not exceed 1.0 ppm.
zene reported for four U.S. cities in 2004 were 1.1 ppb (3.5 μg/m3) for
St. Louis, Missouri, 2.7 ppb (8.6 μg/m3) for Chicago, Illinois, 2.9 ppb Occupational Safety and Health Administration (OSHA, Dept. of Labor)
(9.3 μg/m3) for Los Angeles, California, and 73.5 ppb (234.8 μg/m3) While this section accurately identifies OSHA’s legally enforceable PELs for this substance in 2018,
specific PELs may not reflect the more current studies and may not adequately protect workers.
for Houston, Texas (Clements et al. 2006). Exposure to benzene is Acceptable peak exposure = 50 ppm (maximum duration = 10 min) for select industries.
highest in areas of heavy motor vehicle traffic and around gasoline fill- Ceiling concentration = 25 ppm for select industries.
ing stations. Based on an average benzene concentration of 12.5 ppb Permissible exposure limit (PEL) = 1 ppm; = 10 ppm for select industries.
(40 μg/m3) in the air and exposure of 1 hour per day, daily benzene Short-term exposure limit (STEL) = 5 ppm.
Comprehensive standards for occupational exposure to benzene have been developed.
intake from driving or riding in a motor vehicle is estimated to be
40 μg. Exposure is greater among people who spend significant time Guidelines
in motor vehicles in areas of congested traffic. In addition, pump-
ing of gasoline can be a significant source of benzene exposure; for American Conference of Governmental Industrial Hygienists (ACGIH)
an individual spending 70 minutes per year pumping gasoline, daily Threshold limit value – time-weighted average (TLV-TWA) = 0.5 ppm.
Threshold limit value – short-term exposure limit (TLV-STEL) = 2.5 ppm.
benzene intake is estimated to be 10 μg (ATSDR 1997). According Potential for dermal absorption.
to EPA’s Toxics Release Inventory, environmental releases of ben- Biological exposure index (BEI) (end of shift) = 25 μg/g of creatinine for S-phenylmercapturic acid in
zene decreased from 34 million pounds in 1988 to 6 million pounds urine; = 500 μg/g of creatinine for t,t-muconic acid in urine.
in 2001, when 5 million pounds was released to air and 19,000 lb to National Institute for Occupational Safety and Health (NIOSH, CDC, HHS)
water. In 2007, 775 facilities released 6.3 million pounds of benzene Immediately dangerous to life and health (IDLH) limit = 500 ppm.
(TRI 2009). Benzene levels in water in the vicinity of four manufac- Short-term exposure limit (STEL) = 1 ppm.
turing facilities using or producing benzene ranged from less than 1 Recommended exposure limit (time-weighted-average workday) = 0.1 ppm.
Listed as a potential occupational carcinogen.
to 179 ppb (< 3 to 569 μg/m3) (ATSDR 1997).

National Toxicology Program, Department of Health and Human Services 2

Report on Carcinogens, Fifteenth Edition For definitions of technical terms, see the Glossary.

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National Toxicology Program, Department of Health and Human Services 3