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EC number: 293-260-1 | CAS number: 91052-98-1
- 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:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non-GLP, non guideline study, published in peer reviewed literature, no restrictions, fully adequate for assessment
- Justification for type of information:
- Justification for Category/Read-across approach:
See justification document for category approach and read-across to individual UVCB constituents in section 13.2.
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:
- Investigation of species differences in isobutene (2-methylpropene) metabolism between mice and rats.
- Author:
- Csanady GA, Freise G, Denk B, Filser JG, Cornet M, Rogers V and Laib RJ.
- Year:
- 1 991
- Bibliographic source:
- Arch. Toxicol. 65:100-105
Materials and methods
- Objective of study:
- metabolism
- toxicokinetics
- Principles of method if other than guideline:
- The metabolism of isobutene, and the formation of its primary reactive intermediate 1,1-dimethyloxirane, in rats following inhalation of isobutene was investigated. Comparative investigations of the pharmacokinetics of isobutene were carried out in rats and mice.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- isobutene
- IUPAC Name:
- isobutene
- Reference substance name:
- 2-methylpropene
- EC Number:
- 204-066-3
- EC Name:
- 2-methylpropene
- Cas Number:
- 115-11-7
- Molecular formula:
- C4H8
- IUPAC Name:
- 2-methylprop-1-ene
- Details on test material:
- - Source: Messer Griesheim
- purity >99%
Constituent 1
Constituent 2
- Radiolabelling:
- no
Test animals
- Species:
- other: Rat and mouse
- Strain:
- other: Sprague-Dawley rat; B6C3F1 mice
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS -
- RATS
- Source: Zentralinstitut fur Versuchstierzucht, Hannover, Germany
- Weight at study initiation: 200-300 g
- Diet: Standard diet ad libitum
- Water: ad libitum
- MICE
- Source: Zentralinstitut fur Versuchstierzucht, Hannover, Germany
- Weight at study initiation: 200-300 g
- Diet: Standard diet ad libitum
- Water: ad libitum
Administration / exposure
- Route of administration:
- inhalation
- Vehicle:
- other: air
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: Exposure was carried out as described in Filser and Bolt (1983) Mut Res 120, 57-60
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: closed exposure system (6.4 dm3)
TEST ATMOSPHERE
- The atmosphere was sampled at appropriate time intervals and analyzed with a gas chromatograph equipped with a flame ionization detector - Duration and frequency of treatment / exposure:
- Kinetic studies: Exposure was in a closed system, the duration of exposure was not given.
Identification of 1,1-dimethyloxirane: Exposure for 4 hours.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Kinetic studies: Varying starting concentrations (between 100 and 12,000 ppm ) were used in a closed system.
Identification of 1,1-dimethyloxirane: A constant concentration of 10,000 ppm isobutene was used .
- No. of animals per sex per dose / concentration:
- Kinetic studies: Either two rats or eight mice (in each experiment).
Identification of 1,1-dimethyloxirane: Two rats. - Control animals:
- no
- Positive control reference chemical:
- none
- Details on study design:
- In kinetic studies on isobutene in rats and mice were exposed in closed systems. Pharmacokinetic parameters were calculated using a two-compartment model. In some studies animals were pre-treated with diethyldithiocarbamate or pyrazole to inhibit cytochrome P450.
In studies to identify production of the epoxide metabolite, rats were exposed to a constant concentration of isobutene. - Details on dosing and sampling:
- The cytochrome P450 inhibitors diethyldithiocarbamate (300 mg/kg) or pyrazole (320 mg/kg) were administered i.p.(in saline) as a single dose prior to the start of the experiment.
- Statistics:
- none
Results and discussion
- Preliminary studies:
- not applicable
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Not determined
- Details on distribution in tissues:
- Not determined
- Details on excretion:
- The metabolic elimination of isobutene followed Michaelis-Menten kinetics and showed a classical saturation pattern in both species. Vmax is the maximum metabolic rate and Km(app) is the hypothetical average concentration when metabolic rate is half Vmax. At concentrations up to 500ppm (1140mg/m3) metabolic elimination was first order. In rats Vmax was 340 ± 40 µmol/kg/h and Km (app) was 8,100 ± 2,700 ppm. In mice Vmax was 560 ± 50 µmol/kg/h and Km (app) was 11,000 ± 3,800 ppm. The atmospheric concentration at which Vmax/2 was reached was 1200 ppm for rats and 1800 ppm for mice. Metabolism was saturable in both species and was blocked by diethyldithiocarbamate and pyrazole.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- 1,1 -Dimethyloxirane was formed as a primary reactive metabolite of isobutene in rats and was detected in exhaled air. Under conditions of metabolic saturation (10,000 ppm) the epoxide concentration increased to a maximum of about 0.05 ppm within 104 min.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The metabolism of isobutene (2-methylpropene) in Sprague Dawley rats and B6C3F1 mice follows Michaelis-Menten kinetics. The maximal metabolic elimination rates in rats is half that in mice. The epoxide is a primary reactive metabolite of isobutene in both species. - Executive summary:
Sprague Dawley rats and B6C3F1 mice were exposed to isobutene (2-methylpropene). At concentrations up to 500ppm (1147mg/m3) metabolic elimination was first order. The maximal metabolic elimination rates were 340 µmol/kg/h for rats and 560 µmol/kg/h for mice. The atmospheric concentration at which Vmax/2 was reached was 1200 ppm (2754 mg/m3) for rats and 1800 ppm (4131 mg/m3) for mice. Below atmospheric concentrations of about 500 ppm (1147mg/m3), at steady state, the rate of metabolism of isobutene is directly proportional to its concentration. The epoxide 1,1-dimethyloxirane is formed as a primary reactive metabolite of isobutene in both species and can be detected in exhaled air. Metabolism is saturable in both species and can be blocked by inhibitors of P450 enzymes. When isobutene metabolism is saturated, the concentration of the epoxide in the atmosphere of a closed exposure system is only about 1/15 of that observed for ethene oxide and about 1/100 of that observed for 1,2-epoxy-3-butene as intermediates in the metabolism of ethene or 1,3-butadiene.
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