Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-450-8 | CAS number: 106-99-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP, guideline study with no restrictions, fully adequate for assessment
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 982
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- not applicable
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 1,3-Butadiene
- Cas Number:
- 106-99-0
- Molecular formula:
- C4H6
- IUPAC Name:
- 1,3-Butadiene
- Details on test material:
- - Name of test material (as cited in study report): 1,3-butadiene
- Supplied by: ICI Ltd., Wilton, Middlesborough, Cleveland, UK
- Physical state: colourless, flammable liquid
- Storage condition of test material: room temperature
No further details reported
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Sprague-Dawley CD
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: sexually mature, virgin females, sexually mature males
- Weight at study initiation: 220-266 g (females at mating)
- Housing: Stainless steel mesh cages. Prior to mating: 5 same sex/cage; during mating 1 male and 1 female/cage: following mating females housed individually
- Diet: Pelleted Rat and Mouse Expanded Breeder Diet No. 3, (BP Nutrition (UK) Ltd., Stepfield, Witham, Essex, UK) ad libitum (except during exposure)
- Water: Mains water ad libitum (except during exposure)
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C (intended range)
- Humidity: 55±25% (intended range)
- Air changes (per hr): not reported
- Photoperiod: 12hrs dark / 12hrs light
IN-LIFE DATES: From: 8 January 1981 (animal arrival) To: 27 February 1981
Administration / exposure
- Route of administration:
- inhalation: gas
- Vehicle:
- other: air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole body stainless steel and glass exposure chambers
- Method of holding animals in test chamber: In stainless steel mesh cages
- Generation: 1000-1200L/min air drawn from room, through a filter, into chamber, passed into an expansion chamber where it was mixed with test material. The liquid 1,3-butadiene was volatilised in stainless steel coils in a heat exchanger prior to entry into the expansion chamber. The air/vapour mixture then passed into head of exposure chamber to provide an even distribution of butadiene.
TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography using flame ionisation detector.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- With exception of the occasional deviation all values were within the following pre-set limits: 5, 180-220, 900-1100 and 7360-8640 ppm v/v for 0, 200, 1000 and 8000 ppm v/v exposure concentrations.
- Details on mating procedure:
- - M/F ratio per cage: 1:2
- Length of cohabitation: 10 days
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy. If sperm present, cytology of smear examined as only females in late pro-oestrus or oestrus phases of the cycle were used. - Duration of treatment / exposure:
- Days 6-15 of gestation
- Frequency of treatment:
- 6h/day
- Duration of test:
- Mated females killed on day 20 of gestation.
- No. of animals per sex per dose:
- 24 mated females
- Control animals:
- yes, sham-exposed
- other: positive controls - 250 mg/kg acetylsalicyclic acid orally by gavage
- Details on study design:
- Sex: female
Duration of test: no data
- Dose selection rationale: High dose was limited by safety requirements to be below the lower explosive limit of butadiene in air, intermediate dose matched the AGGIH reccomended levels for occupationally exposed personnel (as given at the date of the study). The low level represented upper range expected to occur in an industrial situation (as estimated at the date of the study).
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice/day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily during gestation
BODY WEIGHT: Yes
- Time schedule for examinations: 0, 3, 6, 9, 12, 15, 18 and 20 of gestation
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: ovaries, uterus
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: - Fetal examinations:
- - Foetal weight: Yes: all per litter
_ Foetal length: Yes: all per litter
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: [2/3rds per litter]
- Skeletal examinations: Yes: [2/3rds per litter]
- Head examinations: Yes: [1/3rds per litter] - Statistics:
- Continuous or semi-continuous responses and some discrete responses: analysis of variance techniques followed by t-test. Kruskal-Wallis test, Wilcoxin rank sum test.
Discrete responses: Fisher's two-sum randomisation test with Monte Carlo simulation. - Indices:
- not given
- Historical control data:
- none
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Dose-related decreased body weight gain during the initial part of the study (up to day 12). At 8000 ppm weight loss during days 1-3 and loss of body weight gain in the other groups. All weight was regained by the end of exposure. Post-implantation loss was slightly but not statistically significantly higher in all 1,3-butadiene exposed groups than in controls, considered to be a consequence of the maternal toxicity.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 200 other: ppm (442 mg/m3)
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
There was no effect at any dose level on pregnancy index, implantation, pre-implantation loss, or on gravid uterus weight. Mean foetal weight and crown/rump length lower in 1,3-butadiene exposed groups (only stat. sig. at 8000 ppm). Higher incidence of minor foetal defects and variants, associated with the smaller foetal size, in the buta-1,3-diene groups. A dose-related increase in the number of major foetal defects, particularly wavy ribs, in the 1,3-butadiene groups, considered to be associated with the dose-related embryonic growth retardation. Other major skeletal defects - abnormalities of the skull, spine, sternum, long bones and ribs - occurred mainly at 8000 ppm and were considered to be due to exposure to 1,3-butadiene. There was no evidence of teratogenicity at dose levels of 200 or 1000 ppm.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1 000 other: ppm (2212 mg/m3)
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
The positive control study verified the susceptibility of the strain of rat used to a known teratogen.
Foetal defect data
Parameter |
Control |
Butadiene 200 ppm |
Butadiene 1,000 ppm |
Butadiene 8,000 ppm |
EXTERNAL AND VISCERAL DEFECTS
|
|
|
|
|
Number of foetuses examined |
450 |
265 |
308 |
294 |
Number showing minor defects only (% of foetuses examined) |
76 (16.9) |
63 (23.8) |
75 (24.4*) |
75 (25.5) |
Number showing major defects (% of foetuses examined) |
0 (0) |
0 (0) |
0 (0) |
2 (0.7) |
SKELETAL DEFECTS
|
|
|
|
|
Number of foetuses examined |
311 |
182 |
215 |
204 |
Number showing minor defects only (% of foetuses examined) |
72 (23.2) |
49 (26.9*1) |
45 (20.9) |
43 (21.1) |
Number showing major defects (% of foetuses examined) |
2 (0.6) |
4 (2.2) |
6 (2.8*) |
12 (5.9**) |
VARIANTS
|
|
|
|
|
Number of foetuses examined |
311 |
182 |
215 |
204 |
Number showing variants (% of foetuses examined) |
267 (85.9) |
164 (90.1) |
185 (86.0) |
199 (97.5*1) |
** - Significantly higher than in the control group p<0.01: Fisher's randomisation test based on the frequencies of affected litters.
* - Significantly higher than in the control group p<0.05: Fisher's randomisation test based on the frequencies of affected litters.
**1- Significantly higher than in the control group p<0.01: Wilcoxon's test
*1- Significantly higher than in the control group p<0.05: Wilcoxon's test
Applicant's summary and conclusion
- Conclusions:
- Exposure of 1,3-butadiene (up to 8000 ppm, 17701 mg/m3) to rats during the period of major organogenesis elicited maternal toxicity and, as a result, embryonic growth retardation at all dose levels tested. There was no evidence of teratogenicity at the the lower exposure levels. (200 and 1000 ppm).
- Executive summary:
Pregnant rats were exposed to 1,3-butadiene (200, 1000 and 8000 ppm; 442, 2212 and 17,701 mg/m3,) 6h/day to rats during the period of major organogenesis ( days 6-15 of gestation) in a pre-natal developmental toxicity study. Maternal toxicity and, as a result, embryonic growth retardation occurred at all dose levels tested. The magnitude of the effect was dose-related. At 8 000 ppm, increased incidences of major foetal defects occurred such as severe wavy ribs. These effects are considered to be indicative of delayed development. There was no evidence of teratogenicity at the lower exposure levels. The NOAEC for teratogenicity was 1000 ppm (2212 mg/m3).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.