SUBSTANCE PROFILES

1,3-Butadiene

CAS No. 106-99-0

Known to be a human carcinogen

First Listed in the Fifth Annual Report on Carcinogens as (1989)

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 information, which indicate a causal

relationship between occupational exposure to 1,3-butadiene and

excess mortality from lymphatic and/or hematopoietic cancers. 1,3-

Butadiene was first listed in the Fifth Annual Report on Carcinogens as

reasonably anticipated to be a human carcinogen based on evidence of its

carcinogenicity in experimental animals; however, the listing was

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

Carcinogens in 2000. Subsequent to the initial animal cancer findings,

1,3-butadiene was shown to be metabolized to mutagenic and

carcinogenic epoxides (epoxybutene and diepoxybutane) in all

mammalian species studied, including humans. A number of human

epidemiology studies have been published, including (1) a cohort study

showing excess risk for lymphosarcoma and reticulosarcoma in workers

who manufactured 1,3-butadiene monomer, (2) a significantly

increased risk for leukemia among production workers in a study of

styrene-butadiene rubber workers in eight plants in the United States

and Canada, and (3) a large excess of leukemia that was associated with

exposure to 1,3-butadiene and not to styrene in a case-control study

within the cohort of styrene-butadiene rubber workers (IARC 1992).

In addition, Ward et al. (1996) found an excess of lymphosarcoma and

reticulosarcoma among 1,3-butadiene production workers in a

previously unstudied chemical plant. Matanoski et al. (1993) reported

that the standardized mortality ratio for leukemia in comparison with

the U.S. population was 1.8 times higher in long-term workers who

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

studied) styrene-butadiene rubber plants with the highest exposure to

butadiene. A second case-control study of the lymphopoietic cancers

among styrene-butadiene rubber workers (new set of controls per case)

confirmed the strong association and significant dose-response effect

between increasing 1,3-butadiene exposure score and increasing risk for

leukemia (Matanoski et al. 1993). Finally, a follow-up study of styrenebutadiene rubber workers concluded that exposure to 1,3-butadiene in

the synthetic rubber industry produced a dose-related increase in the

occurrence of leukemia (Delzell et al. 1996, Macaluso et al. 1996). 

The evidence that butadiene is a human carcinogen is supported

by experimental animal studies, which have shown that 1,3-butadiene

causes both benign and malignant neoplasms at multiple tissue sites in

multiple species, and supporting mechanistic data. Sites of tumor

induction in mice included the hematopoietic system, heart

(hemangiosarcomas), lung, forestomach, harderian gland, preputial

gland, liver, mammary gland, ovary, and kidney (NTP 1984, Huff et

al. 1985, Melnick et al. 1990). Sites of tumor induction in rats

included the pancreas, testis, thyroid gland, mammary gland, uterus,

and Zymbal gland (Owen et al. 1987).

Additional Information Relevant to Carcinogenicity

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 identified in the urine

of a worker exposed to 1,3-butadiene. Activated K-ras genes and

inactivated tumor suppresser 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 of ethylene oxide, an

alkylating agent listed as known to be a human carcinogen (See Ethylene

Oxide profile). The mechanism of tumor induction by 1,3-butadiene in

rodents and humans appears to be due to its metabolism to DNAreactive intermediates resulting in genetic alterations in protooncogenes

and/or tumor suppressor genes (Melnick and Kohn 1995).

Properties

1,3-Butadiene, an aliphatic hydrocarbon, is a colorless, non-corrosive gas

with a mild aromatic or gasoline-like odor and a molecular weight of 54.

The boiling point is –4.4°C and the melting point is –108.9°C. The

vapor pressure is 1,790 mm Hg at 20°C, and the vapor is heavier than air

with a vapor density of 1.87 (IARC 1992). When heated, 1,3-butadiene

emits acrid fumes and is flammable. When exposed to air, it also will

form explosive peroxides that are sensitive to shock or heating above

27°C. 1,3-Butadiene has a log octanol-water partition coefficient of 1.99

and is sparingly soluble in water, slightly soluble in methanol and

ethanol, and soluble in most common organic solvents such as acetone,

diethyl ether, benzene, and cyclohexane. It polymerizes readily in the

presence of sodium or oxygen (Lewis 1992, Budavari et al. 1996, HSDB

2003). The commercial product is 99% pure. It may contain parts-permillion (ppm) levels of butadiene dimer (NTP 1993). 1,3-Butadiene is

transported as a liquified gas under pressure (Morrow 1990).

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 styrenebutadiene 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%),

exports (4%), nitrile rubber (3%), and other uses, including specialty

polymers (2% to 8%) (IARC 1992, ATSDR 1993). The major enduse products for styrene-butadiene and polybutadiene are tires. Other

uses 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 to manufacture

adiponitrile, a nylon intermediate. Butadiene also is 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

from a low of about 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 to about 1.2% from 1980

to 1990. In 1987, 1,3-butadiene ranked 34th among the top 50

chemical commodities produced in the United States and fell slightly

to 36th by the mid 1990s (Morrow 1990, Kirschner 1996, CEN

H2C

C

H

H

C

CH2

REPORT ON CARCINOGENS, ELEVENTH EDITION
SUBSTANCE PROFILES

REPORT ON CARCINOGENS, ELEVENTH EDITION

1997). In 1990, 30 ethylene plants in the United States produced

crude butadiene streams that were processed in 11 extraction plants

(Morrow 1990). Ten U.S. producing companies and 17 U.S.

suppliers were identified in 2003 (ChemSources 2003, SRI 2003).

U.S. demand exceeds the domestic supply in most years; therefore,

imports greatly exceed exports. Imports ranged from about 500 to 900

million pounds (227,000 to 408,000 metric tons) annually from the

late 1970s to the mid 1980s. 1,3-Butadiene imports were

approximately 1.2 to 1.4 billion pounds (544,000 to 635,000 metric

tons) from 1998 to 2000 but decreased to 200 million pounds

(91,000 metric tons) in 2002. Exports ranged from about 94 million

to 145 million pounds (43,000 to 66,000 metric tons) annually in the

late 1970s through the mid 1980s but decreased to about 37.6 million

pounds (17,000 metric tons) in 2000 and 15.2 million pounds (6,900

metric tons) in 2002 (ATSDR 1993, ITA 2001, 2003).

Exposure

The primary route of potential exposure to 1,3-butadiene for the

general population is inhalation. Some exposure may occur from

ingesting contaminated food or water or dermal (skin) contact;

however, these types of exposures are unlikely in most circumstances.

This chemical is not a common contaminant of water supplies, and,

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 rape 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 furnaces at

secondary lead smelting facilities handling automotive lead-acid

batteries that contain plastic battery separators or that have hard rubber

casings and from petroleum refineries (EasternResearchGroupUSA

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 exhaust emissions from motor vehicles as

a product of incomplete combustion of gasoline and diesel oil and

from the thermal breakdown of plastics (ATSDR 1993, Eastern

Research Group USA 1996). California has run dispersion modeling

from a typical freeway source and has estimated that gasoline-fueled

vehicles emit 0.011 grams per mile (Cooper and Reisman 1992). 1,3-

butadiene also is formed naturally as a byproduct of forest fires (HSDB

2003).

Cigarette smoke is also an environmental source of 1,3-butadiene.

Releases into the air in sidestream smoke have been variously estimated

at 152 to 400 μg 1,3-butadiene per cigarette (Ligocki et al. 1995).

Calculations based on 400 μg/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 increase by 13 μg/m3 (Wallace 1991).

1,3-Butadiene has been detected in air samples collected from

urban, suburban, and rural areas. The median daily concentrations

compiled from ambient air samples collected in the United States 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).

However, reported average daily ambient air concentrations 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

(POTW) has been calculated to be 21 tons/yr (19,000 kg/yr)

(EasternResearchGroupUSA 1996).

Occupational exposure to 1,3-butadiene may occur through

inhalation and, to a lesser extent, skin contact (NTP 1984). According

to the National Occupational Exposure Survey (NOES) conducted

from 1981 to 1983, about 52,000 workers, including 1,410 women, at

2,201 facilities were potentially exposed to 1,3-butadiene (NIOSH

1984, 1990). This number does not include workers exposed to

butadiene polymers and copolymers and is consistent with earlier

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

in the National Occupational Hazard Survey (NOHS) conducted from

1972 to 1974 (NIOSH 1976). Health Hazard Evaluation surveys

conducted by NIOSH at six facilities indicated that air concentrations

of 1,3-butadiene ranged 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 > 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 < 1 ppm in 67.8%.

The present OSHA permissible 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).

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

Release Inventory (TRI), total annual on- and off-site releases of 1,3-

butadiene from industrial facilities have declined from more than 7.7

million pounds (3.5 million kilograms) in 1988 to about 2.3 million

pounds (1.0 million kilograms) in 2001. More than 90% was released to

the air (TRI01 2003). 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 the TRI estimate of about 5.2 million

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

Regulations

DOT

Butadienes are considered hazardous materials and special requirements have been

set for marking, labeling, and transporting these materials

EPA

Clean Air Act

Mobile Source Air Toxics: Listed as a Mobile Source Air Toxic for which regulations

are to be developed

NESHAP: Listed as a Hazardous Air Pollutant (HAP)

NSPS: Manufacture of substance is subject to certain provisions for the control of

Volatile Organic Compound (VOC) emissions

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

Urban Air Toxics Strategy: Identified as one of 33 HAPs that present the greatest

threat to public health in urban areas

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

OSHA

Permissible Exposure Limit (PEL) = 1 ppm

Short-Term Exposure Limit = 5 ppm

“Comprehensive Standards” for occupational exposure to this substance have been

developed

Guidelines

ACGIH

Threshold Limit Value - Time-Weighted Average Limit (TLV-TWA) = 2 ppm

NIOSH

Immediately Dangerous to Life and Health (IDLH) = 2000 ppm

Listed as a potential occupational carcinogen 

REFERENCES

ATSDR. 1993. Toxicological Profile for 1,3-Butadiene (Final Report). NTIS Accession No. PB93-110690.

Atlanta, GA: Agency for Toxic Substances and Disease Registry. 135 pp.
SUBSTANCE PROFILES

Budavari, S. M., J. O'Neal, A. Smith and P. E. Heckelman, eds. 1996. The Merck Index. 12th ed. Whitehall,

NJ, Merck & Company, Inc.

CEN. 1986. Key Chemicals. Butadiene. Chem Eng News 64(23): 15.

CEN. 1997. Production: Mixed in 1996. Chem Eng News 75(25): 40-45.

CEN. 1999. Production. Modest gain. Chem Eng News 77(26): 34-39.

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

ChemSources. 2003. Chemical Sources International, Inc. http://www.chemsources.com.

Cooper, F. I. and J. I. Reisman. 1992. The air toxic problem in California: A summary of CARB, BAAQMD and

SCAQMD ambient air monitoring data. Paper no. 92-167.03. Proc Ann Meet Air Waste Manage Assoc 13: 9.

Csadany, G. A., F. P. Guengerich and J. A. Bond. 1992. Comparison of the biotransformation of 1,3-butadiene in rodents and man: Blood concentrations of 1,3-butadiene, its metabolically formed epoxides and

of haemoglobin adducts - relevance of gluthathione depletion. Toxicology 113: 300-305.

Delzell, E., N. Sathiakumar, M. Hovinga, M. Macaluso, J. Julian, R. Larson, P. Cole and D. C. Muir. 1996. A

follow-up study of synthetic rubber workers. Toxicology 113(1-3): 182-9.

EasternResearchGroupUSA. 1996. Locating and Estimating Air Emissions from Sources of 1,3-Butadiene.

Technical Report No. EPA-454/R-96-008. Research Triangle Park, NC: U.S. Environmental Protection

Agency, Office of Air Quality Planning and Standards. 251 pp.

Fajen, J. M., R. A. Lunsford and D. R. Roberts. 1993. Industrial exposure to 1,3-butadiene in monomer,

polymer and end-user industries. IARC Sci Publ (127): 3-13.

HSDB. 2003. Hazardous Substances Database. 1,3-Butadiene. National Library of Medicine. Last updated:

8/29/03. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB and search CAS number. Last accessed:

2/18/04.

Huff, J. E., R. L. Melnick, H. A. Solleveld, J. K. Haseman, M. Powers and R. A. Miller. 1985. Multiple organ

carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure. Science

227(4686): 548-9.

IARC. 1992. Occupational Exposures to Mists and Vapours from Strong Inorganic Acids and Other

Industrial Chemicals. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to

Humans, vol. 54. Lyon, France: International Agency for Research on Cancer. 336 pp.

ITA. 2001. Subheading 2901.24.1000: Buta-1,3-diene. International Trade Administration. U.S. Department

of Commerce. http://www.ita.doc.gov/td/industry/otea/Trade-Detail/.

ITA. 2003. Subheading 2901.24.1000: Buta-1,3-diene. International Trade Administration. U.S. Department

of Commerce. http://www.ita.doc.gov/td/industry/otea/Trade-Detail/.

Kirschner, E. M. 1996. Growth of top 50 chemicals slowed in 1995 from very high 1994 rate. Chem Eng

News 74(15): 16-18, 20, 22.

Lewis, R. J. 1992. Sax's Dangerous Properties of Industrial Materials, 8th ed., vol. 3. New York, NY: Van

Nostrand Reinhold. 

Ligocki, M. P., J. L. Fieber, J. C. Ball, S. A. Pezda, J. M. Heuss, R. T. Paul and H. J. Wimette. 1994.

Projected Emission Trends and Exposure Issues for 1,3-Butadiene. Paper No. 94-WP91.06. Proc Annu

Meet Air Waste Manage Assoc 4B: 18.

Ligocki, M. P., L. Gardner, H. H. Tunggal, J. G. Heiken, R. D. Atkinson and D. Axelrad. 1995. Cumulative

Exposure to Air Toxics: Indoor Sources. Paper No. 95-TP33B.03. Proc Annu Meet Air Waste Manage

Assoc 3A: 16.

Macaluso, M., R. Larson, E. Delzell, N. Sathiakumar, M. Hovinga, J. Julian, D. Muir and P. Cole. 1996.

Leukemia and cumulative exposure to butadiene, styrene and benzene among workers in the synthetic

rubber industry. Toxicology 113(1-3): 190-202.

Matanoski, G., M. Francis, A. Correa-Villasenor, E. Elliott, C. Santos-Burgoa and L. Schwartz. 1993. Cancer

epidemiology among styrene-butadiene rubber workers. IARC Sci Publ (127): 363-74.

Melnick, R. L., J. Huff, B. J. Chou and R. A. Miller. 1990. Carcinogenicity of 1,3-butadiene in C57BL/6 x

C3H F1 mice at low exposure concentrations. Cancer Res 50(20): 6592-9.

Melnick, R. L. and M. C. Kohn. 1995. Mechanistic data indicate that 1,3-butadiene is a human carcinogen.

Carcinogenesis 16(2): 157-63.

Morrow, N. L. 1990. The industrial production and use of 1,3-butadiene. Environ Health Perspect 86: 7-8.

NIOSH. 1976. National Occupational Hazard Survey (1972-74). Cincinnati, OH: Department of Health,

Education and Welfare.

NIOSH. 1984. National Occupational Exposure Survey (1981-83). Cincinnati, OH: U. S. Department of

Health and Human Services. http://www.cdc.gov/noes/noes3/empl0003.html.

NIOSH. 1990. National Occupational Exposure Survey (1981-83). Unpublished provisional data as of

7/1/90. Cincinnati, OH: U. S. Department of Health and Human Services.

NTP. 1984. Toxicology and Carcinogenesis Studies of 1,3-Butadiene (CAS no. 106-99-0) in B6C3F1 Mice

(Inhalation Studies). Technical Report Series No 288. NIH Publication No. 84-2544. Research Triangle

Park, NC: National Toxicology Program. 111 pp.

NTP. 1993. Toxicology and Carcinogenesis Studies of 1,3-Butadiene (CAS no. 106-99-0) in B6C3F1 Mice

(Inhalation Studies). Technical Report Series No 434. NIH Publication No. 93-3165. Research Triangle

Park, NC: National Toxicology Program. 392 pp.

Owen, P. E., J. R. Glaister, I. F. Gaunt and D. H. Pullinger. 1987. Inhalation toxicity studies with 1,3-butadiene. 3. Two year toxicity/carcinogenicity study in rats. Am Ind Hyg Assoc J 48(5): 407-13.

Seaton, M. J., M. H. Follansbee and J. A. Bond. 1995. Oxidation of 1,2-epoxy-3-butene to 1,2:3,4-

diepoxybutane by cDNA-expressed human cytochromes P450 2E1 and 3A4 and human, mouse and rat

liver microsomes. Carcinogenesis 16(10): 2287-93.

Shields, P. G., G. X. Xu, W. J. Blot, J. F. Fraumeni, Jr., G. E. Trivers, E. D. Pellizzari, Y. H. Qu, Y. T. Gao and C.

C. Harris. 1995. Mutagens from heated Chinese and U.S. cooking oils. J Natl Cancer Inst 87(11): 836-41.

SRI. 2003. Directory of Chemical Producers. http://dcp.sric.sri.com/Public/ (Visitor Search).

TRI01. 2003. Toxics Chemical Release Inventory 2001. Data contained in the Toxics Chemical Release

Inventory (TRI). U. S. Environmental Protection Agency Office of Environmental Information.

http://www.epa.gov/triexplorer/.

Wallace, L. A. 1991. Comparison of risks from outdoor and indoor exposure to toxic chemicals. Environ

Health Perspect 95: 7-13.

Ward, E. M., J. M. Fajen, A. M. Ruder, R. A. Rinsky, W. E. Halperin and C. A. Fessler-Flesch. 1996.

Mortality study of workers employed in 1,3-butadiene production units identified from a large chemical

workers cohort. Toxicology 113(1-3): 157-68.

REPORT ON CARCINOGENS, ELEVENTH EDITION