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

1,3-Butadiene

CAS No. 106-99-0

Known to be a human carcinogen

First listed in the Fifth Annual Report on Carcinogens (1989)

H2C

C

H

H

C

CH2

Carcinogenicity

1,3-Butadiene is known to be a human carcinogen based on sufficient 

evidence of carcinogenicity from studies in humans, including epidemiological and mechanistic studies. 1,3-Butadiene was first listed in 

the Fifth Annual Report on Carcinogens in 1989 as reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. The listing was 

revised to known to be a human carcinogen in the Ninth Report on 

Carcinogens in 2000. 

Cancer Studies in Humans 

A number of epidemiological studies have shown an association between occupational exposure to 1,3-butadiene and excess mortality 

from cancer of the lymphatic and hematopoietic systems. These include (1) a cohort study showing increased risk of lymphosarcoma 

and reticulosarcoma in workers who manufactured 1,3-butadiene 

monomer, (2) a study of styrene-butadiene rubber workers in eight 

plants in the United States and Canada showing increased risk of 

leukemia among production workers, and (3) a case-control study 

within the cohort of styrene-butadiene rubber workers showing a 

large excess of leukemia associated with exposure to 1,3-butadiene 

and not to styrene (IARC 1992). In addition, an excess of lymphosarcoma and reticulosarcoma was found among 1,3-butadiene production workers in a previously unstudied chemical plant (Ward et al. 

1996). Excess deaths from leukemia were observed among long-term 

workers who were hired before 1960 and had worked in the three (of 

eight studied) styrene-butadiene rubber plants with the highest exposure to butadiene (standardized mortality ratio = 1.8 in comparison 

with the U.S. population). A second case-control study of styrenebutadiene rubber workers with lymphopoietic cancer (with a new 

set of controls for each case) confirmed the strong association and 

significant dose-response relationship between 1,3-butadiene exposure score and risk of leukemia (Matanoski et al. 1993). Finally, a follow-up study of styrene-butadiene rubber workers in the synthetic 

rubber industry also found a dose-response relationship between 

1,3-butadiene exposure level and the occurrence of leukemia (Delzell et al. 1996, 2006, Macaluso et al. 1996).

Studies on Mechanisms of Carcinogenesis 

1,3-Butadiene appears to cause tumors in humans and rodents 

through its metabolism to DNA-reactive epoxide intermediates, 

which cause genetic alterations in proto-oncogenes or tumor-suppressor genes (Melnick and Kohn 1995). Mouse, rat, and human liver 

microsomes have been shown to oxidize 1,3-butadiene to epoxybutene (Csadany et al. 1992) and to further oxidize the monoepoxide to diepoxybutane (Seaton et al. 1995). These metabolites form 

N′-alkylguanine adducts that have been detected in liver DNA of 

mice exposed to 1,3-butadiene and in the urine of a worker exposed 

to 1,3-butadiene. Activated K-ras oncogenes and inactivated tumorsuppressor genes observed in 1,3-butadiene-induced tumors in mice 

are analogous to genetic alterations frequently observed in a wide 

variety of human cancers. Dose-related increases in hprt mutations 

have been observed in lymphocytes isolated from mice exposed to 

1,3-butadiene or its epoxide metabolites and in occupationally exposed workers. The mutational spectra for 1,3-butadiene and its epoxide metabolites at the hprt locus in mouse lymphocytes are similar to 

the mutational spectrum for ethylene oxide, an alkylating agent listed 

in the Report on Carcinogens as known to be a human carcinogen.

Cancer Studies in Experimental Animals 

There is sufficient evidence for the carcinogenicity of 1,3-butadiene from studies in experimental animals. Inhalation exposure to 

1,3-butadiene caused benign or malignant tumors at several different tissue sites in rodents, including the hematopoietic system, heart 

(hemangiosarcoma), lung, forestomach, Harderian gland, preputial 

gland, liver, mammary gland, ovary, and kidney in mice (NTP 1984, 

Huff et al. 1985, Melnick et al. 1990) and the pancreas, testis, thyroid 

gland, mammary gland, uterus, and Zymbal gland in rats (Owen et 

al. 1987).

Properties

1,3-Butadiene is an olefin which at room temperature is a colorless 

gas with a mild aromatic or gasoline odor. It is insoluble in water but 

soluble in ether, ethanol, acetone, and other organic solvents. It polymerizes readily, especially in the presence of oxygen; therefore, it is 

shipped and stored with an inhibitor to prevent this reaction (Akron 

2009). It is also a dangerous fire hazard. Physical and chemical properties of 1,3-butadiene are listed in the following table.

Property Information

Molecular weight 54.1a

Density 0.6149 g/cm3 at 25°Ca

Melting point –108.966°Ca

Boiling point –4.5°C at 760 mm Hga

Log Kow 1.99b

Water solubility 0.735 g/L at 20°Ca

Vapor pressure 2,110 mm Hg at 25°Ca

Vapor density relative to air 1.87a

Sources: aHSDB 2009, bChemIDplus 2009.

Use

1,3-Butadiene is used primarily as a monomer to manufacture many 

different types of polymers and copolymers and as a chemical intermediate to produce a number of important industrial chemicals. 

More than 75% of the 1,3-butadiene produced goes into synthetic 

rubber products (CEN 1986). The major uses include production of 

styrene-butadiene rubber (30% to 35%), polybutadiene rubber (20% to 

22%), adiponitrile (12% to 15%), styrene-butadiene latex (10%), neoprene rubber (5% to 6%), acrylonitrile-butadiene-styrene resins (5% 

to 6%), and nitrile rubber (3%), exports (4%), and other uses, including production of specialty polymers (2% to 8%) (IARC 1992, ATSDR 

1993). The major end-use products containing styrene-butadiene and 

polybutadiene are tires. Other products include latex adhesives, seals, 

hoses, gaskets, various rubber products, nylon carpet backings, paper 

coatings, paints, pipes, conduits, appliance and electrical equipment 

components, automotive parts, and luggage. The only major nonpolymer use is in the manufacture of adiponitrile, a nylon intermediate. 

Butadiene is also used in the manufacture of the fungicides captan 

and captafol (Morrow 1990, IARC 1992, Kirschner 1996). 

Production

1,3-Butadiene is isolated by distillation or extraction from crude 

butadiene, which is a by-product of ethylene production. Commercial production began in the 1930s (IARC 1992). Between 1980 and 

2002, annual U.S. production of rubber-grade 1,3-butadiene ranged 
Report on Carcinogens, Thirteenth Edition

National Toxicology Program, Department of Health and Human Services 2

from a low of 869,000 metric tons (1.9 billion pounds) in 1982 to a 

high of 2,009,000 metric tons (4.4 billion pounds) in 2000 (IARC 1992, 

CEN 1999, 2003). The average annual change was about 2.5% from 

1992 to 2002 compared with about 1.2% from 1980 to 1990. 1,3-Butadiene ranked 34th among the top 50 chemical commodities produced 

in the United States in 1987, falling to 36th by the mid 1990s (Morrow 

1990, Kirschner 1996, CEN 1997). In 1990, 30 ethylene plants in the 

United States produced crude butadiene streams that were processed 

in 11 extraction plants (Morrow 1990). In 2009, 11 U.S. producers 

and 12 U.S. suppliers of 1,3-butadiene were identified (ChemSources 

2009, SRI 2009). Because U.S. demand for 1,3-butadiene has exceeded 

the domestic supply in most years, imports have greatly exceeded exports. Annual U.S. imports ranged from 500 million to 900 million 

pounds from the late 1970s to the mid 1980s and from 1.2 billion 

to 1.4 billion pounds from 1998 to 2000, decreasing to 200 million 

pounds in 2002 (ATSDR 1993, USITC 2009). In 2008, imports were 

1.7 billion pounds. Annual U.S. exports ranged from 94 million to 

145 million pounds from the late 1970s through the mid 1980s, decreasing to 37.6 million pounds in 2000 and 15.2 million pounds in 

2002. In 2008, exports were 217.6 million pounds.

Exposure

The primary route of potential exposure to 1,3-butadiene for the general population is inhalation. Some exposure may occur through ingestion of contaminated food or water or dermal contact; however, 

these routes of exposure are unlikely under most circumstances. 

1,3-Butadiene is not a common contaminant of water supplies. Although some food packaging contains residual 1,3-butadiene, the 

available data indicate that it does not usually migrate to the food. 

Certain cooking oils, such as rapeseed oil (canola), release 1,3-butadiene when heated (Shields et al. 1995).

Most people are exposed to low levels of 1,3-butadiene in the air, 

because it is released to the environment during its production, use, 

storage, and disposal and is present in gasoline, automobile exhausts, 

and cigarette smoke. 1,3-Butadiene is emitted from petroleum refineries and from furnaces at secondary lead smelting facilities handling 

automotive lead-acid batteries that contain plastic battery separators 

or that have hard rubber casings (EPA 1996). Incomplete combustion 

of a variety of fuels forms 1,3-butadiene as a product. 1,3-Butadiene 

makes up 0.5% to 2% of the total organic gas emissions from most 

types of combustion (Ligocki et al. 1994). It can also be found in motor-vehicle exhaust emissions as a product of incomplete combustion 

of gasoline and diesel oil and from the thermal breakdown of plastics 

(ATSDR 1993, EPA 1996). Through modeling of dispersion from a 

typical freeway source in California, it was estimated that gasolinefueled vehicles emit 0.011 g of 1,3-butadiene per mile (Cooper and 

Reisman 1992). 1,3-Butadiene also is formed naturally as a by-product of forest fires (HSDB 2009). Releases of 1,3-butadiene in sidestream cigarette smoke into the air have been variously estimated at 

152 to 400 μg per cigarette (Ligocki et al. 1995). Calculations based 

on 400 μg per cigarette indicate that 1,3-butadiene concentrations in 

the homes of smokers would be increased by approximately 4 μg/m3, 

and concentrations in air at workplaces allowing smoking would be 

increased by 13 μg/m3

 (Wallace 1991).

According to the U.S. Environmental Protection Agency’s Toxics 

Release Inventory, total industrial environmental releases of 1,3-butadiene declined from more than 7.7 million pounds in 1988 to about 

1.8 million pounds in 2007, of which over 90% was released to air 

(TRI 2009). However, a nationwide 1,3-butadiene inventory (including vehicle emissions and emissions from manufacturing and producing facilities) calculated annual butadiene emissions to air to be 102 

million kilograms (225 million pounds) in 1990 (Ligocki et al. 1994), 

considerably higher than EPA’s estimate of about 5.2 million pounds 

(2.4 million kilograms) for industrial emissions in the same year.

The median daily concentrations of 1,3-butadiene in U.S. ambient air samples collected from 1970 to 1987 were 0.29 ppb in urban 

areas (385 samples), 0.32 ppb in suburban areas (196 samples), and 

0.1 ppb in rural areas (2 samples). The maximum 24-hour average 

concentrations of 1,3-butadiene reported for four U.S. cities in 2004 

were 0.3 ppb for St. Louis, Missouri, 0.5 ppb for Chicago, Illinois, 

and Los Angeles, California, and 37.4 ppb for Houston, Texas (Clements et al. 2006). However, reported average daily concentrations 

of 1,3-butadiene in ambient air within a mile of petrochemical facilities have exceeded 100 ppb, and the highest hourly average concentrations have exceeded 900 ppb (ATSDR 1993). Volatilization of 

1,3-butadiene from wastewaters of styrene-1,3-butadiene copolymer 

production at publicly owned treatment works has been calculated 

to be 21 tons per year (EPA 1996).

Occupational exposure to 1,3-butadiene may occur through inhalation and, to a lesser extent, dermal contact (NTP 1984). The 

National Occupational Exposure Survey (conducted from 1981 to 

1983) estimated that about 52,000 workers at 2,201 facilities, including 1,410 women, potentially were exposed to 1,3-butadiene (NIOSH 

1990). This estimate does not include workers exposed to butadiene 

polymers and copolymers and is consistent with an earlier estimate 

of about 66,000 to 70,000 workers at 3,086 facilities reported in the 

National Occupational Hazard Survey (conducted from 1972 to 1974) 

(NIOSH 1976). Health hazard evaluation surveys conducted by the 

National Institute for Occupational Safety and Health at six facilities found air concentrations of 1,3-butadiene ranging from 0.06 to 

39 ppm. Surveys conducted at many monomer, polymer, and end-user 

plants have reported concentrations ranging from below detection to 

374 ppm (827 mg/m3

). In most cases, 8-hour time-weighted-average 

concentrations were less than 10  ppm (<  22  mg/m3) (IARC 1992, 

ATSDR 1993). For the monomer industry as a whole, 1,3-butadiene 

concentrations were greater than 10 ppm (> 22 mg/m3) in 7.1% of 

the samples, 2 to 10 ppm (4 to 22 mg/m3

) in 12.8%, 1 to 2 ppm (2 to 

4 mg/m3

) in 12.3% and less than 1 ppm (< 2 mg/m3) in 67.8%. The 

Occupational Safety and Health Administration permissible exposure limit is 1 ppm. For the polymer industry as a whole, the corresponding percentages for these four ranges were 3.3%, 7.7%, 3.3%, 

and 85.8%, respectively. The arithmetic mean exposure for personal 

full-shift exposures in the polymer plants was 1.14 ppm (2.57 mg/m3

) 

(Fajen et al. 1993).

Regulations

Department of Transportation (DOT)

Butadienes are considered hazardous materials, and special requirements have been set for marking, 

labeling, and transporting these materials.

Environmental Protection Agency (EPA)

Clean Air Act

Mobile Source Air Toxics: Listed as a mobile source air toxic for which regulations are to be developed.

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

New Source Performance Standards: Manufacture of 1,3‐butadiene is subject to certain provisions for 

the control of volatile organic compound emissions.

Prevention of Accidental Release: Threshold quantity (TQ) = 10,000 lb.

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

threat to public health in urban areas.

Standards have been established for emissions of 1,3‐butadiene from reformulated gasoline and motor 

vehicles.

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.
Report on Carcinogens, Thirteenth Edition

National Toxicology Program, Department of Health and Human Services 3

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.

Permissible exposure limit (PEL) = 1 ppm.

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

Comprehensive standards for occupational exposure to 1,3‐butadiene have been developed.

Guidelines

American Conference of Governmental Industrial Hygienists (ACGIH)

Threshold limit value – time-weighted average (TLV-TWA) = 2 ppm.

National Institute for Occupational Safety and Health (NIOSH)

Immediately dangerous to life and health (IDLH) limit = 2,000 ppm.

Listed as a potential occupational carcinogen.

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