The following information has been extracted from our CHEMINFO database, which also contains hazard control and regulatory information. [More about...] [Sample Record]

Access the complete CHEMINFO database by contacting CCOHS Client Services.

 
SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 377
CCOHS Chemical Name: 1,3-Butadiene

Synonyms:
Biethylene
Bivinyl
Buta-1,3-diene
trans-Butadiene
Divinyl
Erythrene
Pyrrolylene
Vinylethylene
Butadiene (non-specific name)

Chemical Name French: 1,3-Butadiène
Chemical Name Spanish: 1,3-Butadieno
CAS Registry Number: 106-99-0
UN/NA Number(s): 1010
RTECS Number(s): EI9275000
EU EINECS/ELINCS Number: 203-450-8
Chemical Family: Unsaturated aliphatic hydrocarbon / diolefin / diene
Molecular Formula: C4-H6
Structural Formula: CH2=CH-CH=CH2

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless gas at room temperature or liquid at temperatures below -4.4 deg C, with a mild aromatic or gasoline-like odour.(2,18,19)

Odour Threshold:
Wide range of reported values: 0.099 to 76 ppm. Acceptable values are: 0.45 ppm (1.0 mg/m3) (detection); 1.1 ppm (2.4 mg/m3) (recognition) (20)

Warning Properties:
NOT RELIABLE - odour threshold is about the same magnitude as the TLV.

Composition/Purity:
1,3-Butadiene is available as a liquefied gas under pressure in several grades ranging in minimal purity from 99.0 to 99.8%. Typical impurities include 1,2-butadiene, propadiene, acetylenes (methyl, ethyl, vinyl), dimers, isoprene, C4 hydrocarbons (e.g. n-butane, isobutane, isobutylene and 2-butene), C5 hydrocarbons, carbonyls (e.g. acetaldehyde), 4-vinylcyclohexene, peroxides and sulfur. The inhibitor most commonly used to prevent polymerization and polymeric peroxide formation is tert-butylcatechol, at a concentration of 100- 115 ppm. Other inhibitors include di-n-butylamine, 2,6-di-tert-butyl-p-cresol and phenyl-betanaphthylamine.(2,4,18,19,21,22) Inhibited 1,3-butadiene is shipped as a liquefied compressed gas under its own vapour pressure of about 145 kPa (21 psig) at 21.1 deg C (70 deg F).(18)

Uses and Occurrences:
1,3-Butadiene is used mainly as a monomer or comonomer in the manufacture of synthetic elastomers, predominantly styrene-butadiene rubber (SBR), polybutadiene rubber (BR), polychloroprene (neoprene) and nitrile rubber (NR); and polymers and resins, including acrylonitrile-butadiene-styrene (ABS) and styrene-butadiene copolymer (latex). It is also used in the production of adiponitrile, ethylidene norbornene, trans-1,4-hexadiene, sulfolane, 1,5,9- cyclodecatriene, and other chemicals. Other uses include the manufacture of fungicides and some dyes.(2,19,22)
It is extracted as a by-product of petroleum refining and cracking and is also produced by dehydrogenation of butene and butane fractions.(19,22) It is not known to occur as a natural product, but is emitted in automobile exhaust, in smoke generated during house fires and in cigarette smoke.(2,4)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless gas at room temperature or liquid at temperatures below -4.4 deg C, with a mild gasoline-like odour. EXTREMELY FLAMMABLE GAS. Liquid can accumulate static charge by flow, splashing or agitation. Gas is heavier than air and may spread long distances. Distant ignition and flashback are possible. COMPRESSED GAS. DANGEROUSLY REACTIVE. Gas or uninhibited liquid may polymerize explosively when exposed to elevated temperatures, air, sunlight, rust, and in the presence of incompatible materials, such as peroxides. Cylinders and closed containers may rupture violently if heated. May form explosive peroxides in the presence of air or oxygen. Can decomposes explosively at high temperatures and pressure. High concentrations can displace oxygen in the air and cause life-threatening asphyxiation (suffocation). Confined space hazard. Rapid evaporation of the liquid may cause frostbite. CANCER HAZARD - can cause cancer. MUTAGEN - may cause inheritable genetic damage.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Inhalation of high concentrations (several thousand ppm) of 1,3-butadiene gas can cause irritation of the nose, throat and lungs. Very high concentrations can cause depression of the central nervous system (CNS) with symptoms such as headache, nausea, dizziness, drowsiness, and confusion. High concentrations can also displace oxygen in the air and cause life-threatening asphyxiation (suffocation). These effects have been observed in animals and humans.
No short-term health effects were experienced by employees following exposure to 1000 ppm for an unspecified time. Slight lung irritation was experienced at 2000-4000 ppm. At 8000 ppm, with an 8-hour exposure, lung irritation was experienced.(1) Coughing and symptoms of CNS depression were experienced by volunteers exposed to 8000 ppm for 8 hours.(2,3) Another author reported that irritation of the nasal passages, throat and lungs was experienced by employees exposed to 1,3-butadiene (concentration unspecified) during the manufacture of rubber in the 1940s.(4)

Skin Contact:
Inhalation is the primary occupational health concern. Exposure to very high airborne concentrations (several thousand ppm) can irritate the skin.(4,5)
Contact with liquefied gas escaping from its pressurized cylinder may cause frostbite.(2,4) Symptoms of mild frostbite include numbness, prickling and itching in the affected area. Symptoms of more severe frostbite include a burning sensation and stiffness of the affected area. The skin may become waxy white or yellow. Blistering, tissue death and gangrene may also develop in severe cases.

Eye Contact:
Inhalation is the primary occupational health concern. Exposure to very high concentrations (several thousand ppm) of 1,3-butadiene can irritate the eyes.(5) Slight irritation of the eyes was experienced by volunteers exposed to 2000-4000 ppm for an unspecified period of time. Irritation was experienced by volunteers exposed to 8000 ppm for 8 hours.(1) Another author reports that blurred vision, as well as eye irritation, was experienced by 2 men during 6-7 hour exposures to 2000 or 4000 ppm.(4)
Contact with liquefied gas escaping from its high pressure cylinder may cause freezing of the eye. Permanent eye damage or blindness could result.

Ingestion:
Ingestion is not an applicable route of exposure for gases.

Effects of Long-Term (Chronic) Exposure

Because of limitations in the study designs, no firm conclusions can be drawn from the results of two cross-sectional studies of styrene-butadiene and 1,3-butadiene manufacturing workers in which no or slight harmful effects on the blood were observed.(2,4,5) Harmful effects on the blood and blood-forming system, kidneys, liver and lungs have been observed in animal studies.
No firm conclusions can be drawn from reports of effects (including blood disorders, kidney malfunction, irritation of the respiratory tract and stomach and various skin disorders) in people occupationally exposed to 1,3-butadiene, mainly in the ex-USSR and Bulgaria. Exposure levels are unknown and few details are available.(5)

Carcinogenicity:

1,3-Butadiene is carcinogenic to humans based on sufficient evidence in humans of an increased risk for leukemias.(37)
A number of studies of employees in the styrene-butadiene rubber industry and in the butadiene manufacturing industry have been conducted. Although many of the studies are limited in design (for example, by mixed exposures and/or small population size), some show an association between 1,3-butadiene exposure and leukemia, lymphosarcoma or other lymphatic cancers. One study examined the mortality of around 17,000 workers from eight facilities in the US and Canada. An increased mortality from chronic lymphocytic and myelogenous leukemia was seen in the most highly exposed workers, especially those hired before and during the 1950s or those employed for long periods of time (greater than or equal to 10 years).(37) Tumours in multiple organs have been observed in studies using rats and mice.

The International Agency for Research on Cancer (IARC) has concluded that this chemical is carcinogenic to humans (Group 1).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as a suspected human carcinogen (A2).

The US National Toxicology Program (NTP) has listed this chemical as a known human carcinogen.

Teratogenicity and Embryotoxicity:
No human information was located. Fetotoxicity and/or teratogenicity have been observed in the offspring of mice and rats exposed to 1,3-butadiene by inhalation, but the observed effects are considered secondary to maternal toxicity.

Reproductive Toxicity:
No human information was located. No conclusions can be made about the potential reproductive effects of 1,3-butadiene based on the available animal information because the effects observed occurred in the presence of significant other toxicity in the animals. However, 1,3-butadiene is mutagenic to sperm, which has reproductive implications.

Mutagenicity:
Despite their limitations, some human studies have shown mutagenic effects in the blood cells of people occupationally exposed to 1,3-butadiene.(4,7) Animal information clearly indicates that 1,3-butadiene is mutagenic to both somatic and germ cells. Positive and negative results have been obtained in cultured mammalian cells, including some tests with human cells.(5)

Toxicologically Synergistic Materials:
There is no specific information available.

Potential for Accumulation:
1,3-Butadiene does not accumulate in the body. It is absorbed from the lungs, distributed into the blood and transported to different tissues and organs. It is metabolized to 1,2-epoxy-3-butene, which can be further metabolized to 1,2:3,4-diepoxybutane and finally to carbon dioxide. Elimination occurs mainly in the urine and exhaled air (carbon dioxide and volatile metabolites, such as 1,2-epoxy-3-butene) with small amounts excreted in the feces.(1,2,4)


SECTION 4. FIRST AID MEASURES

Inhalation:
Take proper precautions to ensure your own safety before attempting rescue (e.g. wear appropriate protective equipment, use the "buddy" system). Remove source of contamination or move victim to fresh air. If breathing has stopped, trained personnel should begin artificial respiration or, if the heart has stopped, cardiopulmonary resuscitation (CPR) immediately. Obtain medical attention immediately.

Skin Contact:
GAS: No effects expected. At concentrations likely to cause skin irritation, inhalation exposure is the primary concern. LIQUEFIED GAS: Avoid direct contact. Wear chemical protective gloves, if necessary. Quickly remove victim from source of contamination and briefly flush with lukewarm, gently flowing water until the chemical is removed. DO NOT attempt to rewarm the affected area on site. DO NOT rub or apply dry heat. Gently remove clothing or jewelry that may restrict circulation. Carefully cut around clothing that sticks to the skin and remove the rest of the garment. Loosely cover the affected area with a sterile dressing. DO NOT allow the victim to drink alcohol or smoke. Quickly transport victim to an emergency care facility.

Eye Contact:
GAS: No effects expected. At concentrations likely to cause skin irritation, inhalation exposure is the primary concern. LIQUEFIED GAS: Quickly remove victim from source of contamination. Immediately and briefly flush with lukewarm, gently flowing water until the chemical is removed. DO NOT attempt to rewarm. Cover both eyes with a sterile dressing. DO NOT allow victim to drink alcohol or smoke. Quickly transport victim to an emergency care facility.

Ingestion:
Ingestion is not an applicable route of exposure to gases.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest).
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.

Note to Physicians:
Some jurisdictions have specific regulations for 1,3-butadiene. These regulations may include requirements for medical surveillance programs, including pre-employment and pre-placement examinations, periodic medical examinations, clinical tests, health education and record keeping. Obtain detailed information from the appropriate government agency in relevant jurisdictions.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
-76 deg C (-105 deg F) (2,23); -85 deg C (-121 deg F) (22) (closed cup)

Lower Flammable (Explosive) Limit (LFL/LEL):
1.4% at 20 deg C and 101.3 kPa (22); 2.0% (18,19)

Upper Flammable (Explosive) Limit (UFL/UEL):
11.5% (18,19); 12% (23); 16.3% at 20 deg C and 101.3 kPa (22)

Autoignition (Ignition) Temperature:
415-420 deg C (779-788 deg F) (19,22,24)

Sensitivity to Mechanical Impact:
Inhibited 1,3-butadiene is normally stable. Uninhibited 1,3-butadiene may form explosive, shock- and heat-sensitive organic peroxides when exposed to air.(19,25)

Sensitivity to Static Charge:
1,3-Butadiene liquid can accumulate static charge by flow, splashing or agitation due its low electrical conductivity.(26) Gas in the flammable range can be ignited readily by static discharge of sufficient energy. Minimum ignition energy: 0.13 millijoules (26,27) At fast flow rates, can ignite spontaneously on exposure to air.(26)

Combustion and Thermal Decomposition Products:
Toxic, irritating chemicals.

Fire Hazard Summary:
Extremely flammable gas (above -4.4 deg C) or liquid (below -4.4 deg C). Can form explosive mixtures with air which will readily ignite at room temperature. Low ignition energy. Liquid can accumulate static charge by flow, splashing or agitation. Gas can be ignited by a static charge. Gas is colder and heavier than air and may hug the ground and travel a considerable distance to a source of ignition and flash back to a leak or open container. Explosion and toxicity hazard is increased in a confined space. Compressed gas. Heat from a fire can cause a rapid build-up of pressure inside cylinders, which may cause explosive rupture and suddenly release large amounts of flammable gas. Loss of inhibitor or excessive heat from a fire may cause spontaneous polymerization, which can cause containers to rupture violently. 1,3-Butadiene gas is uninhibited and may form polymers in vents or flame arrestors of storage tanks, resulting in blockage. The gas can also form explosive peroxides in air.

Extinguishing Media:
Carbon dioxide, dry chemical powder, foam or water spray or fog. Water will not be effective as an extinguisher because it cannot cool 1,3-butadiene below its flash point, and may also increase evolution of the gas from the liquid.(29)

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or protected location. Approach fire from upwind to avoid hazardous gas and toxic decomposition products.
For fires involving flammable gases, the best procedure is to stop the flow of gas before attempting to extinguish the fire. To extinguish the fire, while allowing continued flow of the gas, is extremely dangerous. The gas could form an explosive mixture with air and reignite, which may cause far more damage than if the original fire had been allowed to burn. In some cases, extinguishing the fire with carbon dioxide or dry chemical powder may be necessary to permit immediate access to valves to shut off the flow of gas. However, this must be done carefully. If it is not possible to stop the flow of gas and if there is no risk to the surrounding area, it is preferable to allow continued burning, while protecting exposed materials with water spray to prevent ignition of other combustible materials, until the flow of gas can be stopped.
Gas clouds may be controlled by water spray or fog. The addition of water to pools of liquefied 1,3-butadiene may increase evolution of toxic gas.
Isolate materials not yet involved in the fire and protect personnel. Handle damaged cylinders with extreme care. Move cylinders from fire area if this can be done without risk. Otherwise, fire-exposed containers, cylinders tanks or pipelines should be cooled by application of hose streams and this should begin as soon as possible (within the first several minutes) and should concentrate on any unwetted portions of the container. Take care not to get water inside a container. Reverse flow into a cylinder may cause rupture. No part of a cylinder should be subjected to a temperature higher than 52 deg C (approximately 125 deg F). The heat generated by the fire can cause polymerization and explosive decomposition may occur. If this is not possible, use unmanned monitor nozzles and immediately evacuate the area.
For a massive fire in a large area, use unmanned hose holder or monitor nozzles; if this is not possible withdraw from fire area and allow fire to burn. Stay away from ends of tanks, but be aware that flying material from ruptured tanks may travel in any direction. Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank due to fire. After the fire has been extinguished, explosives atmospheres may linger. Before entering such an area especially confined areas, check the atmosphere with an appropriate monitoring device. In addition, because of the danger of life-threatening asphyxiation (suffocation), check the atmosphere for sufficient oxygen.
1,3-Butadiene is very toxic and a suspected human carcinogen. Do not enter fire area without wearing specialized protective/equipment suitable for the situation. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. A full-body encapsulating chemical resistant suit with positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Health: 2 - Intense or continued (but not chronic) exposure could cause temporary incapacitation or possible residual injury.
NFPA - Flammability: 4 - Will rapidly or completely vaporize at atmospheric pressure and normal ambient temperature, or readily disperse in air and burn readily.
NFPA - Instability: 2 - Undergoes violent chemical change at elevated temperatures and pressures, or reacts violently with water, or may form explosive mixtures with water.

SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 54.09

Conversion Factor:
1 ppm = 2.21 mg/m3; 1 mg/m3 = 0.452 ppm at 25 deg C (calculated)

Physical State: Gas
Melting Point: -108.9 deg C (-164 deg F) at 101.3 kPa (18,19,22)
Boiling Point: -4.41 deg C (24.1 deg F) at 101.3 kPa (18,19,22)
Relative Density (Specific Gravity): Not applicable (gas)
Solubility in Water: Sparingly soluble (50-73.5 mg/100 mL at 20-25 deg C and 101.3 kPa) (2,18,24,29,31)
Solubility in Other Liquids: Soluble in ethanol, methanol, diethyl ether and benzene; very soluble in acetone and higher-boiling polar solvents, such as methylpyrrolidone.(2,4,22,31)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = 1.99 (2,4,31)
pH Value: Not applicable
Viscosity-Dynamic: 0.00075 mPa.s (0.00075 centipoise) at 20 deg C and 101.33 kPa (24) 0.33 mPa.s (0.33 centipoise) at -40 deg C; 0.25 mPa.s (0.25 centipoise) at 0 deg C (19,22,24)
Surface Tension: 20.7 mN/m (20.7 dynes/cm) at -40 deg C (liquid) (24)
Vapour Density: 1.87 at 15 deg C (1) (air = 1)
Vapour Pressure: 248.9 kPa (2.46 atm) at 21.1 deg C (18,24); 428.8 kPa (4.23 atm) at 40 deg C (22)
Vapour Pressure at 50 deg C: 558.75 kPa (5.51 atm) at 50 deg C (calculated) (24)
Saturation Vapour Concentration: Not applicable; gas at normal temperatures.
Evaporation Rate: Not applicable; gas at normal temperatures
Critical Temperature: 152 deg C (305.6 deg F) (18,19,22)
Critical Pressure: 4320-4330 kPa (42.63-42.73 atm) (18,19,22)

Other Physical Properties:
TRIPLE POINT: -108.9 deg C (-164.1 deg F) at 0.069 kPa abs (18)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Stable when inhibited. Explosive, shock- and heat-sensitive polymeric peroxides may be produced in the presence of air.(19,25,28) The polyperoxide formed is insoluble in 1,3-butadiene and forms a separate layer, thus increasing the hazard.(25)

Hazardous Polymerization:
Polymerization may occur during production, storage and transportation with a rapid release of pressure and heat. The reaction may be initiated by high temperatures, oxygen, peroxides and rust.(19,22,29) 1,3-Butadiene can dimerize slowly at room temperature (0.00015%/hour) and moderately at 100 deg C (1.1%/hour).(19,24)

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


AIR or OXYGEN - forms an unstable polyperoxide, which can explode.(19,23,25,28)
STRONG OXIDIZERS (e.g. chlorine, chlorine dioxide, nitrogen oxides, nitrates, perchlorates, peroxides,) - increased risk of fire, explosion or violent reaction.(23,25,28)
COPPER, COPPER ALLOYS or MONEL - can form unstable acetylides, which can detonate.(29)
ALUMINUM TETRAHYDROBORATE - explodes immediately.(25,28)
BUTEN-3-YNE (VINYLACETYLENE) - react exothermally and decomposes explosively.(25)
CROTONALDEHYHDE - may explode.(23,25)
BORON TRIFLUORIDE and PHENOL - may catalyze polymerization with increase in pressure.(23,25)
CONCENTRATED SODIUM NITRITE SOLUTIONS (5%) - forms black sludge, which when dry, will ignite and burn when heated to 150 deg C, even in the absence of air.(25)

Hazardous Decomposition Products:
Uninhibited 1,3-butadiene may form explosive, shock- and heat-sensitive organic peroxides when exposed to air.(19,25)

Conditions to Avoid:
Heat, sparks, static discharge, open flames, elevated temperatures, air, sunlight

Corrosivity to Metals:
1,3-Butadiene is not corrosive to the common metals, such as steel, stainless steel, nickel, aluminum and cast iron.(32)


SECTION 11. TOXICOLOGICAL INFORMATION

LC50 (rat): 132,000 ppm (290,000 mg/m3) (4-hour exposure) (2,4)
LC50 (mouse): 87,000 ppm (4-hour exposure); cited as 123,000 ppm (270,000 mg/m3) (2-hour exposure) (1,5)

Eye Irritation:

Irritation of the inner eyelids was observed in rats and mice following exposure to very high concentrations (90,000-140,000 ppm) of the gas for an unspecified time.(1) No signs of eye injury were observed in rabbits or dogs during or following exposure to up to 6700 ppm for 8 months.(1)

Effects of Short-Term (Acute) Exposure:

Inhalation:
Irritation of the nose and respiratory tract and breathing effects (respiratory obstruction) were observed in rats and mice following exposure to very high concentrations (90,000-140,000 ppm) for an unspecified time.(1) Reduced body weight was observed in mice during and after exposure to 1250 ppm (males only) to 8000 ppm for 2 weeks.(1) Secretion from the nose or slight incoordination were observed in rats starting on the second day of exposure to 1000 or 8000 ppm in a long-term toxicity study.(1)

Effects of Long-Term (Chronic) Exposure:

Inhalation:
Blood system effects (changes in bone marrow stem cell development, reduction in white and red blood cells and an increase in the volume of circulating red blood cells) were observed in several studies involving male mice exposed to 1250 ppm for 6-31 weeks.(1,4,8,9) Effects on red blood cell enzymes, grooming activity and salivation were observed in rats exposed to 1000-8000 ppm for 13 weeks.(1,5) No firm conclusions can be drawn from a number of other studies using small numbers of animals.(1) No firm conclusions can be drawn from reports of visible changes in the liver, kidneys, spleen, throat and heart observed in female rats exposed to 0.45-14 ppm for 81 days. Details about statistical significance and reversibility are not available.(5)

Carcinogenicity:
Several well-conducted studies have shown that 1,3-butadiene is carcinogenic to experimental animals. Tumours in multiple organs have been observed in studies using both rats and mice, although they were observed at much lower exposure levels in mice. The International Agency for Research on Cancer (IARC) has concluded that there is sufficient evidence for the carcinogenicity of 1,3-butadiene to experimental animals.(5,37)
In rats, tumours of the breast, thyroid (females only) and testes (Leydig cell tumours) were observed after exposure to 1000 ppm and 8000 ppm 1,3-butadiene for 105 weeks (females) or 111 weeks (males). Tumours of the pancreas (males only), uterus, and Zymbal gland were also observed, but were not considered treatment-related. Low survival rates were observed among both control and exposed groups.(1,5,10) In mice, cancers of the lymph (malignant lymphomas) and blood (hemangiosarcoma) systems were observed after exposure to 625 ppm or 1250 ppm 1,3-butadiene (greater than 98.9% pure) for 60 or 61 weeks in a study that was terminated early because of fatal tumours. Lung, stomach, breast, ovary and liver (females) tumours were also observed. The increases in lymph system cancer and lung tumours were dose related in males and all types of tumours were dose-related in females.(1,5) Lymphomas and hemangiosarcomas of the heart were observed in both male and female mice exposed to lower concentrations (6.25-625 ppm) for 104 weeks in a later study. Survival was low (less than 35%) at all exposure levels, except the lowest. Deaths were primarily attributed to tumours. Females developed lung tumours at the lowest exposure level and were more sensitive than males. It was concluded that the results provided clear evidence of carcinogenicity of 1,3-butadiene in male and female mice.(11)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
Fetotoxicity and/or teratogenicity have been observed in the offspring of mice and rats exposed to 1,3-butadiene by inhalation, but the observed effects are considered secondary to maternal toxicity.
Mice and rats were exposed to 0, 40, 200 or 1000 ppm on days 6-15 of pregnancy (6 hr/d). Maternal toxicity (decreased body weight gain) was observed in rats exposed to 1000 ppm. No developmental effects were observed in the rat offspring. Maternal toxicity (decreased body weight gain) was observed in mice exposed to 200 or 1000 ppm. Mouse fetal weights were reduced at 200 and 1000 ppm and minor skeletal abnormalities were observed at 200 and/or 1000 ppm. There was also a slight reduction in male fetal body weight at 40 ppm, which was considered of questionable biological significance. Overall, relatively minor developmental effects were observed in the presence of maternal toxicity.(12) Rats were exposed to 0, 200, 1000 or 8000 ppm on days 6-15 of pregnancy (6 hr/d). Maternal toxicity (reduced body weight gain) was observed at all exposure levels. There was a slight increase in post-implantation loss, which was not statistically significant, in all exposure groups. There was a marginal, concentration-related reduction in fetal weight and size, which reached statistical significance at 8000 ppm. Signs of delayed development (increased incidences of wavy ribs, irregular rib ossification and incomplete ossification) and teratogenicity (major defects - skull, spine, sternum, long bones and ribs) were also observed in the offspring of mothers exposed to 8000 ppm. The developmental effects observed are considered secondary to maternal toxicity.(13,36)

Reproductive Toxicity:
There is insufficient information available to evaluate the potential reproductive toxicity of 1,3-butadiene. However, there are several studies that have conclusively shown that 1,3-butadiene is mutagenic to sperm. This effect clearly has reproductive implications but is considered to be mutagenicity rather than reproductive toxicity. Refer to the mutagenicity section below for details. No conclusions can be drawn from two other studies in which effects (decreased number of litters and gonadal atrophy) were seen in the presence of significant harmful effects on the parents and/or statistical significance was not evaluated.(1,14)

Mutagenicity:
Positive results were obtained in a number of tests using live animals including germ cell tests (dominant lethal tests) and somatic cell tests (including alkylation of DNA, micronuclei, chromosomal aberrations and sister chromatid exchanges). Mice have been shown to be more sensitive than rats.
Positive results (dominant lethal mutations) were obtained for male mice exposed to 12.5 or 1250 ppm 1,3-butadiene for 10 weeks (6 hr/d; 5 d/wk) (15) or to 65 or 130 ppm for 4 weeks (6 hr/d; 5 d/wk) (36, unconfirmed) or to 1300 ppm for 5 days (6 hr/d) (36, unconfirmed). Negative results (dominant lethal mutations) were obtained for male rats exposed to 0, 65, 400 or 1250 1,3-butadiene for 10 weeks (6 hr/d; 5 d/wk).(15) A positive result was obtained in live rats and mice in tests for alkylation of DNA.(2,16) Both positive and negative results have been obtained in tests for DNA crosslinks using live mice and rats.(2,4,5) Positive results were obtained in tests for micronuclei, chromosomal aberrations and sister chromatid exchanges (SCEs) in which mice were exposed by inhalation. Negative results were obtained in rats.(1,2,4,17)
Positive results have been obtained in cultured mammalian cells (a mouse lymphoma test).(1) Positive and negative results have been obtained in bacteria.(1,5)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Dutch expert committee for occupational standards. Health-based recommended occupational exposure limits for 1,3-butadiene. Report RA 5/90. Directorate-General of Labour of the Ministry of Social Affairs and Employment, Aug. 1990
(2) Sorsa, M., et al. 1,3-Butadiene. Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals; 113. Arbete och Halsa. Vol. 36 (1994)
(3) Crouch, C.N., et al. Inhalation toxicity studies with 1,3-butadiene. 2. 3 month toxicity study in rats. American Industrial Hygiene Association Journal. Vol. 40, no. 9 (Sept. 1979). p. 796-802
(4) Himmelstein, M. W., et al. Toxicology and epidemiology of 1,3-butadiene. Critical Reviews in Toxicology. Vol. 17, no. 1 (1997). p. 1-108
(5) International Agency for Research on Cancer. 1,3-Butadiene. In: IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 54. Occupational exposures to mists and vapours from strong inorganic acids; and other organic industrial chemicals. World Health Organization, 1992. p. 237-285
(6) Report on Carcinogens. 11th ed. US Department of Health and Human Services, Public Health Service, National Toxicology Program
(7) Legator, M.S., et al. Elevated somatic cell mutant frequencies and altered DNA repair responses in nonsmoking workers exposed to 1,3-butadiene. In: Butadiene and styrene: assessment of health hazards. IARC Scientific Publications No. 127. Edited by M. Sorsa, et al. International Agency for Research on Cancer, 1993. p. 253-263
(8) Irons, R.D., et al. Macrocytic-megaloblastic anemia in male NIS Swiss mice following repeated exposure to 1,3-butadiene. Toxicology and Applied Pharmacology. Vol. 85, no. 3 (Sept. 1986). p. 450-455
(9) Leiderman, L.J., et al. Altered hematopoietic stem cell development in male B6C3F1 mice following exposure to 1,3-butadiene. Experimental and Molecular Pathology. Vol. 44, no. 1 (1986). p. 50-56
(10) Owen, P.E., et al. Inhalation toxicity studies with 1,3-butadiene: 3 two year toxicity/carcinogenicity study in rats. American Industrial Hygiene Journal. Vol. 48, no. 5 (May 1987). p. 407-413
(11) Melnick, R.L., et al. Carcinogenicity of 1,3-butadiene in C57BL/6 x C3H F1 mice at low exposure concentrations. Cancer Research. Vol. 50, no. 20 (Oct. 15, 1990). p. 6592-6599
(12) Morrissey, R.E., et al. Overview of reproductive and developmental toxicity studies of 1,3-butadiene in rodents. Environmental Health Perspectives. Vol. 86 (June 1990). p. 79-84
(13) Irvine, L.F.H. 1,3-Butadiene: inhalation teratogenicity study in the rat. Final report with addendum to final report. Report No. 2788-522/3. Hazleton Laboratories Europe Ltd., Nov. 1981 and Mar. 1982
(14) Carpenter, C.P., et al. Studies on the inhalation of 1,3-butadiene with a comparison of its narcotic effect with benzol, toluol, and styrene and a note on the elimination of styrene by the human. Journal of Industrial Hygiene and Toxicology. Vol. 26, no. 3 (Mar. 1944). p. 69-78
(15) Anderson, D., et al. Male-mediated F1 effects in mice exposed to 1,3- butadiene. In: Butadiene and styrene: assessment of health hazards. IARC Scientific Publications No. 127. Edited by M. Sorsa, et al. International Agency for Research on Cancer, 1993. p. 171-181
(16) Kreiling, R., et al. Alkylation of nuclear proteins and DNA after exposure of rats and mice to [1,4-14C]1,3-butadiene. Toxicology Letters. Vol. 30, no. 2 (Feb. 1986). p. 131-136
(17) Cunningham, M.J., et al. In vivo sister chromatid exchange and micronucleus induction studies with 1,3-butadiene in B6C3F1 mice and Sprague- Dawley rats. Mutagenesis. Vol. 1, no. 6 (1986). p. 449-452
(18) Compressed Gas Association. 1,3-Butadiene (butadiene). In: Handbook of compressed gases. 4th ed. Kluwer Academic Publishers, 1999. p. 287-294
(19) Sun, H.N., et al. Butadiene. In: Kirk-Othmer encyclopedia of chemical technology. 4th ed. Vol. 4. John Wiley and Sons, 1992. p. 663-690
(20) Odor thresholds for chemicals with established occupational health standards. American Industrial Hygiene Association, 1989. p. 13, 47
(21) Matheson gas products. Matheson, 1990. p. 6
(22) Muller, H.J., et al. Butadiene. In: Ullmann's encyclopedia of industrial chemistry. 5th completely revised ed. Volume A 4. VCH Verlagsgesellschaft, 1985. p. 431-446
(23) Fire protection guide to hazardous materials. 13th ed. Edited by A.B. Spencer, et al. National Fire Protection Association, 2002. NFPA 325; NFPA 49; NFPA 491
(24) Braker, W., et al. 1,3-Butadiene. In: Matheson gas data book. 6th ed. Matheson Gas Products, 1980. p. 79-87
(25) Urben, P.G., ed. Bretherick's handbook of reactive chemical hazards. 5th ed. Vol. 1. Butterworth-Heinemann, Ltd., 1995. p. 514-516, 1846
(26) Chemical safety sheets: working safely with hazardous chemicals. Kluwer Academic Publishers, 1991. p. 130
(27) Haase, H. Electrostatic hazards: their evaluation and control. Translated by M. Wald. Verlag Chemie, 1997. p. 108
(28) The Sigma-Aldrich library of chemical safety data. Ed II. Vol. 1. Sigma-Aldrich Corporation, 1988. p. 597B
(29) Emergency action guide for butadiene. Association of American Railroads, Jan. 1988
(30) Emergency response planning guidelines. AIHA Journal. Vol. 56, no. 2 (1995). p. 202
(31) HSDB database record for 1,3-butadiene. Last revision date: 98/06/02
(32) Corrosion data survey: metals section. 6th ed. National Association of Corrosion Engineers, 1985. p. 24-5 to 25-5
(33) NIOSH pocket guide to chemical hazards. US National Institute for Occupational Safety and Health, June 1997
(34) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(35) European Communities (EC). Commission Directive 2001/59/EC. Aug. 6, 2001
(36) European Union Risk Assessment Report. 1,3-Butadiene. CAS No. 106-99-0. 1st Priority List. Vol. 20. European Chemicals Bureau, 2002
(37) Grosse, Y., et al. Carcinogenicity of 1,3-butadiene, ethylene oxide, vinyl chloride, vinyl fluoride, and vinyl bromide. The Lancet Oncology. Vol. 8 (Aug. 2007). p. 679-680

Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 2000-04-02

Revision Indicators:
ERPG 2001-03-01
EU classification 2002-02-11
EU risks 2002-02-11
TDG 2002-05-29
US transport 2002-12-23
Stability/reactivity comments 2003-04-17
PEL-TWA final 2004-01-29
PEL-STEL final 2004-01-29
PEL final comments 2004-01-29
PEL-TWA transitional 2004-01-29
PEL transitional comments 2004-01-29
Resistance of materials for PPE 2004-04-08
Toxicological info 2005-04-05
Teratogenicity/embryotoxicity 2005-04-05
WHMIS health effects 2005-04-05
Vapour pressure at 50 deg C 2005-09-26
Relative density 2006-09-28
Bibliography 2007-09-17
Carcinogenicity 2007-09-17
Handling 2007-09-17
WHMIS detailed classification 2007-09-17
Emergency overview 2007-09-17



©2007 Canadian  Centre  for  Occupational  Health  &  Safety  
www.ccohs.ca  E-mail: clientservices@ccohs.ca  Fax: (905) 572-2206  Phone: (905) 572-2981  
Mail:  250  Main  Street  East,  Hamilton  Ontario  L8N  1H6