Report on Carcinogens, Thirteenth Edition

National Toxicology Program, Department of Health and Human Services

For Table of Contents, see home page: http://ntp.niehs.nih.gov/go/roc13

Benzene

CAS No. 71-43-2

Known to be a human carcinogen

First listed in the First Annual Report on Carcinogens (1980)

Carcinogenicity

Benzene is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.

Cancer Studies in Humans

Case reports and case series have reported leukemia (mostly acute 

myelogenous leukemia, also known as acute myeloid or myelocytic 

leukemia) in individuals exposed to benzene. The strongest epidemiological evidence that benzene causes cancer is from several cohort studies in various industries and geographical locations, which 

found that occupational exposure to benzene increased the risk of 

mortality from leukemia (mainly acute myelogenous leukemia). Casecontrol studies also reported that exposure to benzene increased the 

risk of leukemia, but the usefulness of these studies was limited by 

poorly defined exposures and mixed exposure patterns (IARC 1974, 

1982, 1987).

Since benzene was reviewed for listing in the First Annual Report 

on Carcinogens, numerous epidemiological studies of benzene exposure and cancer have been published. The International Agency for 

Research on Cancer (IARC) evaluated benzene in 2012 and concluded 

that there was sufficient evidence for the carcinogenicity of benzene 

in humans, based on a causal relationship with myeloid leukemia/

acute non-lymphocytic leukemia (IARC 2012). IARC also concluded 

that there was limited evidence of carcinogenicity based on a positive association between exposure to benzene and acute lymphocytic leukemia, chronic lymphocytic leukemia, multiple myeloma, 

and non-Hodgkin lymphoma. 

Cancer Studies in Experimental Animals

Studies in experimental animals, including many published after 

benzene was listed in the First Annual Report on Carcinogens, have 

demonstrated that benzene causes cancer at numerous tissue sites in 

rodents. Oral exposure to benzene caused cancer of the Zymbal gland 

(carcinoma) in rats and mice of both sexes, cancer of the oral cavity (squamous-cell carcinoma) in rats of both sexes, malignant lymphoma and lung cancer (alveolar/bronchiolar carcinoma) in mice of 

both sexes, skin cancer (squamous-cell carcinoma) in male rats, benign tumors of the Harderian gland (adenoma) and cancer of the preputial gland (carcinoma) in male mice, and benign ovarian tumors 

and cancer of the mammary gland (carcinoma and carcinosarcoma) 

in female mice (NTP 1986, Huff et al. 1989). Inhalation exposure to 

benzene caused tumors at many tissue sites in rats and a tendency 

towards induction of lymphoid tumors in mice. Benzene administered by intraperitoneal injection caused benign lung tumors in male 

mice (IARC 1982, 1987). Dermal application of benzene caused benign skin tumors in transgenic mice carrying the v-Ha-ras oncogene, which increases their susceptibility to carcinogens (Blanchard

et al. 1998, Spalding et al. 1999, French and Saulnier 2000). In heterozygous p53-deficient mice (with only one functional copy of the 

p53 tumor-suppressor gene), benzene administered by stomach tube 

caused cancer (sarcoma) of head and neck, thoracic cavity, and subcutaneous tissue (French et al. 2001, Hulla et al. 2001).

Properties

Benzene is the primary aromatic compound. It exists at room temperature as a clear, colorless-to-yellow liquid with an aromatic odor. 

It is only slightly soluble in water, but it is miscible with alcohol, ether, 

chloroform, carbon disulfide, acetone, oils, carbon tetrachloride, glacial acetic acid, and most other organic solvents. Benzene is highly 

flammable (Akron 2009). Physical and chemical properties of benzene are listed in the following table.

Property Information

Molecular weight 78.1

Specific gravity 0.8787 at 15°C/4°C

Melting point 5.5°C

Boiling point 80.1°C

Log Kow 2.13

Water solubility 1.79 g/L at 25°C

Vapor pressure 94.8 mm Hg at 25°C

Vapor density relative to air 2.8

Source: HSDB 2009.

Use

Benzene is used primarily as a solvent in the chemical and pharmaceutical industries, as a starting material and intermediate in the synthesis of numerous chemicals, and in gasoline. As a raw material, it is 

used in the synthesis of ethylbenzene (used to produce styrene) (53%), 

cumene (used to produce phenol and acetone) (22%), cyclohexane 

(12%), nitrobenzene (used to produce aniline and other chemicals) 

(5%), detergent alkylate (linear alkylbenzene sulfonates) (3%), and 

chlorobenzenes and other products (5%). Benzene is used as an additive in gasoline, but it also is present naturally in gasoline, because 

it occurs naturally in crude oil and is a by-product of oil-refining processes. The percentage of benzene in unleaded gasoline is approximately 1% to 2% by volume (ATSDR 1997, HSDB 2009). 

Production

Benzene has been produced commercially from coal since 1849 and 

from petroleum since 1941. Since 1959, the major U.S. source of 

benzene has been petroleum (IARC 1989). In 1994, benzene ranked 

17th in production volume among chemicals produced in the United 

States. U.S. production of benzene increased from 5.4 million metric tons (12.0 billion pounds) in 1992 to 7.2 million metric tons (15.8 

billion pounds) in 2002, an average increase of 2.8% per year (CEN 

2003). Annual production during this period was highest in 2000, at 

8.1 million metric tons (17.8 billion pounds). In 2009, 59 U.S. manufacturers (SRI 2009) and 24 U.S. suppliers of benzene were identified (ChemSources 2009). In 2002, U.S. imports of benzene totaled 

over 4 billion liters (1.1 billion gallons), which greatly exceeded exports of 6 million liters (1.6 million gallons). This trend continued in 

2008, when 3.9 billion liters (1.03 billion gallons) was imported and 

49.6 million liters (13.1 million gallons) was exported (USITC 2009).

Exposure

The primary route of human exposure to benzene is inhalation of 

ambient air. Benzene is present in the atmosphere both from natural sources, which include forest fires and oil seeps, and from industrial sources, which include automobile exhaust, industrial 

emissions, and fuel evaporation from gasoline filling stations. Benzene has been measured in outdoor air at various U.S. locations at 

concentrations ranging from 0.02 ppb (0.06 μg/m3

) in a rural area to 

112 ppb (356 μg/m3

) in an urban area. The maximum 24-hour average concentrations of benzene 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) 
Report on Carcinogens, Thirteenth Edition

National Toxicology Program, Department of Health and Human Services 2

for Chicago, Illinois, 2.9 ppb (9.3 μg/m3) for Los Angeles, California, and 73.5 ppb (234.8 μg/m3

) for Houston, Texas (Clements et al.

2006). Exposure to benzene is highest in areas of heavy motor vehicle traffic and around gasoline filling stations. Based on an average 

benzene concentration of 12.5 ppb (40 μg/m3

) in the air and exposure of 1 hour per day, daily benzene intake from driving or riding in 

a motor vehicle is estimated to be 40 μg. Exposure is greater among 

people who spend significant time in motor vehicles in areas of congested traffic. In addition, pumping of gasoline can be a significant 

source of benzene exposure; for an individual spending 70 minutes 

per year pumping gasoline, daily benzene intake is estimated to be 

10 μg (ATSDR 1997). 

The general population can also be exposed to benzene by inhaling air containing tobacco smoke, drinking contaminated water, or 

eating contaminated food. About half of the total national exposure 

to benzene comes from cigarette smoke. The median level of benzene 

was 2.2 ppb (7 μg/m3

) in 185 homes without smokers and 3.3 ppb 

(10.5 μg/m3

) in 343 homes with one or more smokers. Amounts of 

benzene measured per cigarette ranged from 5.9 to 75 μg in mainstream smoke and from 345 to 653 μg in sidestream smoke. Benzene 

has been detected in fruits, vegetables, nuts, dairy products, eggs, 

and fish. In a 1992 survey of more than 50 foods, benzene concentrations in foods containing both benzoate and ascorbate food additives ranged from less than 1 to 38 ppb (< 3 to 120 μg/m3

) (ATSDR, 

1997). According to the U.S. Environmental Protection Agency’s Toxics Release Inventory, environmental releases of benzene decreased 

from 34 million pounds in 1988 to 6 million pounds in 2001, when 

5 million pounds was released to air and 19,000 lb to water. In 2007, 

775 facilities released 6.3 million pounds of benzene (TRI 2009). Benzene levels in water in the vicinity of four manufacturing facilities using or producing benzene ranged from less than 1 to 179 ppb (< 3 to 

569 μg/m3

) (ATSDR, 1997). 

Occupational exposure may occur during production of benzene 

or use of substances containing it. In the vulcanization step of tire 

manufacturing, benzene was measured at concentrations of up to 

27.2 mg/m3

, resulting in an estimated daily intake of 0.0045 mg/kg of 

body weight for workers (Durmusoglu 2007). The National Occupational Health Survey (conducted from 1972 to 1974) estimated that 

147,600 U.S. workers potentially were exposed to benzene (NIOSH 

1976), and the National Occupational Exposure Survey (conducted 

from 1981 to 1983) estimated that about 272,000 workers, including 

143,000 women, potentially were exposed to benzene (NIOSH 1990). 

Regulations

Coast Guard, Department of Homeland Security

Comprehensive regulations have been established for safe transport of benzene on ships and barges.

Consumer Product Safety Commission (CPSC)

Products containing 5% or more by weight of benzene are considered hazardous and require special 

labeling.

Solvents for paints or other surface-coating materials containing 10% or more by weight of benzene 

require special packaging.

Department of Transportation (DOT)

Benzene is considered a hazardous material, and special requirements have been set for marking, 

labeling, and transporting this material.

Environmental Protection Agency (EPA)

Clean Air Act

Comprehensive regulations have been developed to control benzene levels in gasoline and benzene 

emissions from motor vehicles.

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 

content of 1.3 vol% may not be exceeded.

National Emission Standards for Hazardous Air Pollutants: Listed as a hazardous air pollutant.

New Source Performance Standards: Manufacture is subject to certain provisions for the control of 

volatile organic compound emissions.

Urban Air Toxics Strategy: Identified as one of 33 hazardous air pollutants that present the greatest 

threat to public health in urban areas.

Clean Water Act

Designated a hazardous substance.

Effluent Guidelines: Listed as a toxic pollutant.

Water Quality Criteria: Based on fish or shellfish and water consumption = 2.2 μg/L; based on fish or 

shellfish consumption only = 51 μg/L.

Comprehensive Environmental Response, Compensation, and Liability Act

Reportable quantity (RQ) = 10 lb.

Emergency Planning and Community Right-To-Know Act

Toxics Release Inventory: Listed substance subject to reporting requirements.

Resource Conservation and Recovery Act

Characteristic Hazardous Waste: Toxicity characteristic leaching procedure (TCLP) threshold = 0.5 mg/L.

Listed Hazardous Waste: Waste codes for which the listing is based wholly or partly on the presence of 

benzene = U019, F005, F024, F025, F037, F038, K085, K104, K105, K141, K142, K143, K144, K145, 

K147, K151, K159, K169, K171, K172.

Listed as a hazardous constituent of waste.

Safe Drinking Water Act

Maximum contaminant level (MCL) = 0.005 mg/L.

Food and Drug Administration (FDA)

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.

Occupational Safety and Health Administration (OSHA)

While this section accurately identifies OSHA’s legally enforceable PELs for this substance in 2010, 

specific PELs may not reflect the more current studies and may not adequately protect workers.

Acceptable peak exposure = 50 ppm (maximum duration = 10 min) for select industries.

Ceiling concentration = 25 ppm for select industries.

Permissible exposure limit (PEL) = 1 ppm; = 10 ppm for select industries.

Short-term exposure limit (STEL) = 5 ppm.

Comprehensive standards for occupational exposure to benzene have been developed.

Guidelines

American Conference of Governmental Industrial Hygienists (ACGIH)

Threshold limit value – time-weighted average (TLV-TWA) = 0.5 ppm.

Threshold limit value – short-term exposure limit (TLV-STEL) = 2.5 ppm.

Potential for dermal absorption.

National Institute for Occupational Safety and Health (NIOSH)

Immediately dangerous to life and health (IDLH) limit = 500 ppm.

Short-term exposure limit (STEL) = 1 ppm.

Recommended exposure limit (time-weighted-average workday) = 0.1 ppm.

Listed as a potential occupational carcinogen.

References

Akron. 2009. The Chemical Database. The Department of Chemistry at the University of Akron. http://ull.

chemistry.uakron.edu/erd and search on CAS number. Last accessed: 10/20/09.

ATSDR. 1997. Toxicological Profile for Benzene. Update (Final Report). NTIS Accession No. PB98-101157. 

Atlanta, GA: Agency for Toxic Substances and Disease Registry. 459 pp.

Blanchard KT, Ball DJ, Holden HE, Furst SM, Stoltz JH, Stoll RE. 1998. Dermal carcinogenicity in 

transgenic mice: relative responsiveness of male and female hemizygous and homozygous Tg.AC mice 

to 12-O-tetradecanoylphorbol 13-acetate (TPA) and benzene. Toxicol Pathol 26(4): 541-547.

CEN. 2003. Production inches up in most countries. Chem Eng News 81(27): 51-61.

ChemSources. 2009. Chem Sources - Chemical Search. Chemical Sources International. http://www.

chemsources.com/chemonline.html and search on benzene. Last accessed: 10/20/09.

Clements AL, Flatt VB, Fraser MP, Hamilton WJ, Ledvina PS, Mathur SK, Tamhane A, Ward JB. 2006. The 

Control of Air Toxics: Toxicology Motivation and Houston Implications. Rice University Department of Civil 

and Environmental Engineering. http://hydrology.rice.edu/ceve/fraser/FINAL%20MASTER.pdf.

Durmusoglu E, Aslan S, Can E, Bulut Z. 2007. Health risk assessment of workers’ exposure to organic 

compounds in a tire factory. Hum Ecol Risk Assess 13: 209-222.

French JE, Lacks GD, Trempus C, Dunnick JK, Foley J, Mahler J, Tice RR, Tennant RW. 2001. Loss of 

heterozygosity frequency at the Trp53 locus in p53-deficient (+/–) mouse tumors is carcinogen-and 

tissue-dependent. Carcinogenesis 22(1): 99-106.

French JE, Saulnier M. 2000. Benzene leukemogenesis: an environmental carcinogen-induced tissuespecific model of neoplasia using genetically altered mouse models. J Toxicol Environ Health A 61(5-6): 

377-379.

HSDB. 2009. Hazardous Substances Data Bank. National Library of Medicine. http://toxnet.nlm.nih.gov/

cgi-bin/sis/htmlgen?HSDB and search on CAS number. Last accessed: 10/20/09.
Report on Carcinogens, Thirteenth Edition

National Toxicology Program, Department of Health and Human Services 3

Huff JE, Haseman JK, DeMarini DM, Eustis S, Maronpot RR, Peters AC, Persing RL, Chrisp CE, Jacobs AC. 

1989. Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice. Environ Health Perspect 

82: 125-163.

Hulla JE, French JE, Dunnick JK. 2001. Chromosome 11 allelotypes reflect a mechanism of chemical 

carcinogenesis in heterozygous p53-deficient mice. Carcinogenesis 22(1): 89-98.

IARC. 1974. Benzene. In Some Anti-Thyroid And Related Substances, Nitrofurans And Industrial Chemicals. 

IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 7. Lyon, France: 

International Agency for Research on Cancer. pp. 203-221.

IARC. 1982. Benzene. In Some Industrial Chemicals and Dyestuffs. IARC Monographs on the Evaluation 

of Carcinogenic Risk of Chemicals to Humans, vol. 29. Lyon, France: International Agency for Research 

on Cancer. pp. 93-148.

IARC. 1987. Benzene. In Overall Evaluations of Carcinogenicity. IARC Monographs on the Evaluation of 

Carcinogenic Risk of Chemicals to Humans, suppl 7. Lyon, France: International Agency for Research on 

Cancer. pp. 120-122.

IARC. 1989. Occupational exposures in petroleum refining. In Occupational Exposures in Petroleum Refining; 

Crude Oil and Major Petroleum Fuels. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals 

to Humans, vol. 45. Lyon, France: International Agency for Research on Cancer. pp. 39-118.

NIOSH. 1976. National Occupational Hazard Survey (1972-74). DHEW (NIOSH) Publication No. 78-114. 

Cincinnati, OH: National Institute for Occupational Safety and Health.

NIOSH. 1990. National Occupational Exposure Survey (1981-83). National Institute for Occupational Safety 

and Health. Last updated: 7/1/90. http://www.cdc.gov/noes/noes1/09070sic.html.

NTP. 1986. Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1

Mice (Gavage Studies). Technical Report Series no. 289. NIH Publication no. 86-2545. Research Triangle 

Park, NC, and Bethesda, MD: National Toxicology Program. 277 pp.

Spalding JW, French JE, Tice RR, Furedi-Machacek M, Haseman JK, Tennant RW. 1999. Development of a 

transgenic mouse model for carcinogenesis bioassays: evaluation of chemically induced skin tumors in 

Tg.AC mice. Toxicol Sci 49(2): 241-254.

SRI. 2009. Directory of Chemical Producers. Menlo Park, CA: SRI Consulting. Database edition. Last accessed: 

10/20/09.

TRI. 2009. TRI Explorer Chemical Report. U.S. Environmental Protection Agency. http://www.epa.gov/

triexplorer and select Benzene.

USITC. 2009. USITC Interactive Tariff and Trade DataWeb. United States International Trade Commission. 

http://dataweb.usitc.gov/scripts/user_set.asp and search on HTS no. 2900220. Last accessed: 10/20/09.