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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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non-GLP, near guideline study published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise 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:
- publication
- Title:
- Comparison of blood concentrations of 1,3-butadiene and butadiene epoxides in mice and rats exposed to 1,3-butadiene by inhalation
- Author:
- Himmelstein MW, Turner MJ, Asgharian B and Bond JA
- Year:
- 1 994
- Bibliographic source:
- Carcinogenesis. 15; 1479-1486
Materials and methods
- Objective of study:
- absorption
- metabolism
- Principles of method if other than guideline:
- To investigate species differences in 1,3-butadiene metabolism, the in vivo blood concentrations of 1,3-butadiene, butadiene monoxide and butadiene diepoxide in rats and mice were measured during and following 6 hr exposures to inhaled 1,3-butadiene.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Reference substance 001
- Cas Number:
- 106-99-0
- Molecular formula:
- C4 H6
- 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
- Source: obtained from two sources:
- BD 15,000 ppm (certified concentration) in nitrogen from Scott Specialty Gases (Plumsteadville, PA).
- Pure buta-1,3-diene (>99%): Aldrich Chemical Company (Milwaukee, WI, USA).
Constituent 1
Constituent 2
- Radiolabelling:
- no
Test animals
- Species:
- other: rat and mouse
- Strain:
- other: Sprague-Dawley CD and B6C3F1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Male Sprague-Dawley CD rats (Crl:CDIBR) and male B6C3F1 mice (B6C3FI/Cr1BR)
- Source: Charles River
- Age: 8-11 weeks
- Weight: 25-33 g for mice and 321-403 g for rats
- Housing: No data
- Diet: A standard rodent diet (NIH-07; Zeigler Brothers) ad libitum, except during exposure
- Water: Ad libitum, except during exposure
- Acclimation period: At least 10 days
- Determined to be free of viral antibodies
ENVIRONMENTAL CONDITIONS
- Temperature: 22±2°C
- Humidity: 55%
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: No data
Administration / exposure
- Route of administration:
- inhalation
- Vehicle:
- other: air
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: nose only
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Concentrated 1,3-butadiene (15,000 ppm) from a cylinder was mixed with clean dry air to achieve target concentrations in the nose-only exposure unit.
- The resulting mixture was conducted through an infrared gas analyzer to continuously monitor the concentration of 1,3-butadiene at the inlet to the unit. A second gas analyzer was used to measure the concentration of buta-1,3-diene at the inlet, exposure port and chamber exhaust. The latter gas analyzer automatically rotated through the three sampling locations at 10 min intervals. - Duration and frequency of treatment / exposure:
- Up to 6 hours in a continuous exposure system
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Target concentrations of 62.5, 625 and 1250 ppm buta-1,3-diene. Actual concentrations were very similar to the targets.
- No. of animals per sex per dose / concentration:
- 5-12 rats per exposure
13-19 mice per exposure. - Control animals:
- no
- Positive control reference chemical:
- none
- Details on study design:
- 1,3-Butadiene, butadiene monoxide and butadiene diepoxide were quantified in the blood of rats and mice during and following inhalation of 1,3-butadiene at the three exposure concentrations. Respiratory measurements were also made on the rats and mice.
Buta-1,3-diene was determined using a head-space equilibration technique followed by gas chromatography. The epoxides were quantified by electron-impact ionization gas chromatography-mass spectrometry - Details on dosing and sampling:
- Measurement of breathing frequency and tidal volume: Rats or mice (one animal per exposure) were placed in body plethysmograph tubes. Minute volume was calculated as the product of breathing frequency and tidal volume.
Collection of blood: During exposure, blood samples for the measurement of buta-1,3-diene and butadiene monoxide were collected at 2, 3, 4 and 6 h of exposure. Blood samples for the measurement of butadiene diepoxide were collected at 3 and 6 h of exposure. After exposure, blood samples for all of these were collected at 2-10 min intervals up to 30 min post-exposure. A minimum of three blood samples per time point were collected. - Statistics:
- none
Results and discussion
- Preliminary studies:
- none
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- 1,3-Butadiene concentrations in blood were at steady state levels 2 hr after the start of exposure and remained constant during exposure to 62.5, 625 and 1250 ppm. The concentration in mice blood was 2-fold that of rats. 1,3-Butadiene levels in blood were not proportional to the inhaled concentrations suggesting saturable uptake in both species. Levels declined rapidly after exposure, such that by 30 min they were 1-12% of the steady state concentration.
- Details on distribution in tissues:
- not determined
- Details on excretion:
- not determined
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Butadiene monoxide was detected in blood of rats and mice but levels in mice were 4-8 times higher than in rats. Levels declined rapidly after exposure, such that by 20 min they were 10-40% of the steady state concentration. Butadiene diepoxide was only detected in the blood of mice.
Any other information on results incl. tables
1,3-Butadiene, and butadiene mono and diepoxide were quantified in the blood of rats and mice during and following inhalation of 1,3-butadiene at the three exposure concentrations.
The respiratory measurements in rats and mice were unaffected by 1,3-butadiene.
Blood concentrations of buta-1,3-diene and its mono and diepoxide are shown in the table.
1,3-Butadiene exposure concentration (ppm) |
Mouse |
Rat |
1,3-Butadiene concentration in blood (µM) |
||
62.5 |
2.4± 0.2 |
1.3± 0.04 |
625 |
37± 3 |
18± 0.7 |
1250 |
58± 3 |
37± 1.4 |
1,3-Butadiene monoxide concentration in blood (µM) |
||
62.5 |
0.56± 0.04 |
0.07± 0.01 |
625 |
3.7± 0.4 |
0.94± 0.04 |
1250 |
8.6± 0.6 |
1.3± 0.09 |
1,3-Butadiene diepoxide concentration in blood (µM) |
||
62.5 |
0.65± 0.1 |
ND |
625 |
1.9± 0.2 |
ND |
1250 |
2.5± 0.4 |
ND |
ND= not detected
These data suggest that the greater sensitivity of mice to 1,3-butadiene-induced toxicity and carcinogenicity compared to rats, may be partially explained by the increased metabolism resulting in higher concentrations of the mono and diepoxides.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: bioaccumulation potential cannot be judged based on study results
The greater sensitivity of mice to 1,3-butadiene-induced toxicity and carcinogenicity compared to rats, may be partially explained by increased metabolism resulting in higher concentrations of the mono and diepoxides. - Executive summary:
The concentrations of 1,3-butadiene and its mono and diepoxides were determined in the blood of rats and mice during and after exposure to inhaled buta-1,3-diene at 62.5, 625 or 1250 ppm (138, 1383 or 2766 mg/m3) for 6 hr. Steady-state blood concentrations of 1,3-butadiene were higher in mice than in rats. The concentration of 1,3-butadiene in blood was not directly proportional to the inhaled concentration of 1,3-butadiene, suggesting that the uptake of 1,3-butadiene was saturable at the highest inhaled concentration. In mice the respective 1,3-butadiene steady-state monoxide concentrations in blood were 0.6, 3.7 and 8.6 µM, compared to concentrations of 0.07, 0.94 and 1.3 µM in rats. Mice, but not rats, had quantifiable levels of the diepoxide in the blood. These data suggest that the greater sensitivity of mice to 1,3-butadiene-induced toxicity and carcinogenicity compared to rats, may be partially explained by the increased metabolism resulting in higher concentrations of the mono and diepoxides.
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