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EC number: 207-975-3 | CAS number: 503-74-2
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 3-methylbutan-1-ol
- EC Number:
- 204-633-5
- EC Name:
- 3-methylbutan-1-ol
- Cas Number:
- 123-51-3
- IUPAC Name:
- 3-methylbutan-1-ol
- Details on test material:
- - Name of test material (as cited in study report): 3-methylbutanol-1
- Substance type: aliphatic alcohol
- Physical state: liquid
- Analytical purity: 99.7%
- Purity test date: 1995-08-24
- Lot/batch No.: S18954
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga GmbH
- Age at study initiation: 8 weeks
- Weight at study initiation: males 33-35.4 g; females 25-37 g
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: in Macrolon cages type I
- Diet: Altromin TPF N1324 (pellets, poor in nitrosamines)
- Water: tap water ad libitum
ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: 0.25% Methocel K4M premium solution
- Justification for choice of solvent/vehicle: improved water solubility of the TS
- Concentration of test material in vehicle: 150 g/L
- Amount of vehicle (if gavage or dermal): 10 mL/kg bw
- Lot/batch no.: ZDP 33/97; released for toxicological investigations until August 29, 1997 - Duration of treatment / exposure:
- single dose
Doses / concentrations
- Remarks:
- Doses / Concentrations:
1500 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Justification for choice of positive controls: significant increase of polychromatic erythrocytes expected as proof of proper function of the test system
- Route of administration: oral gavage
- Doses / concentrations: 19.75 mg/kg bw
Examinations
- Tissues and cell types examined:
- polychromatic erythrocytes
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
Based on results (toxicity) of pilot study with 1000 and 2000 mg/kg bw
TREATMENT AND SAMPLING TIMES:
24 and 48 hr post treatment
DETAILS OF SLIDE PREPARATION:
Bone marrow cells were prepared from two femura of each animal, suspendend in fetal calf serum, wasshed, resuspended, and bone marrow smears were prepared from the resulting cell suspension. After 3 hours of air drying, the slides were stained according to a modified Giemsa
staining method described by Gollapudi and Kamra (1979) using Giemsa's solution with Weise buffer solution and mounted in Entellan.
METHOD OF ANALYSIS:
Microscopic evaluation. A total of 2000 polychromatic erythrocytes per animal were scored for micronuclei using Zeiss light microscopes with plane optics (magnification: 1250x). Round particles with about 1/20 - 1/5 the diameter of an erythrocyte that stained violet, like nucleic material, were scored as micronuclei. They were differentiated from granules by thorough examination at different optical levels. Only erythrocytes with a distinct bluish touch were evaluated as polychromatic.
For determination of the quotient of normochromatic to polychromatic erythrocytes, both erythrocyte stages were screened for micronuclei and counted separately up to a total of 1000 erythrocytes per animaL - Evaluation criteria:
- As predetermined in the study protocol, the test materials are classified as mutagenic or non-mutagenic in this system according to the following rules:
A positive effect in this test system is defined by the occurrence of mean MN-PCE values of a treatment group which are statistically significantly higher than those of the actual negative control. A prerequisite for this is, however, that these values are above those predetermined as historical negative controls of our laboratory
An indispensable prerequisite for evaluating the results of such investigations is the occurrence of significant positive effects in the actual positive control group.
A test material showing no positive effect is defined as a non-mutagen in this test system. In this case the study is terminated.
If a positive effect in a single test group occurs (Le. dose-independently), a repeat experiment has to be considered. In case that no positive effects occur in that experiment the test material is defined as a non-mutagen. The single positive effect of the first experiment is interpreted as a randomly occurring event of no biological significance.
A test material is defined as mutagenic in this system if dose-related or single, reproducible (in independent experiments) positive effects occur. Establishment of dose-dependent effects of the test material is preferable. - Statistics:
- Numerical calculations were made usin a softeware package.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 1000 and 2000 mg/kg bw
- Clinical signs of toxicity in test animals: prone position, dyspnea, weight loss, but no mortality
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no
- Ratio of NCE/PCE (for Micronucleus assay): (report, table 6)
Solvent, 24 h: 1.1 +/-0.3
Test substance, 24 h: 1.0 +/- 0.2
Test substance, 48 h: 1.1 +/- 0.1
CPA, 24 h: 1.0 +/- 0.2
- Appropriateness of dose levels and route: yes
- Statistical evaluation: yes
Any other information on results incl. tables
Clinical findings
Number of animals showing symptoms/number of treated animals per dose group
Symptoms |
Dose 3-methylbutanol |
|
0 |
1500 |
|
Dyspnea |
0/10 |
16/20 |
Body weight:
A significant decrease in body weight was observed in animals at 1500 mg 3-methylbutanol/kg bw.
Micronucleated cells:
2000 polychromatic erythrocytes per animal were evaluated, 5 males and 5 females per group. The solvent control group values were all in the historical control range of the laboratory. Statistically increased number of erythrocytes with micronuclei (p<0.01) was established with cyclophosphamide. Of the groups receiving 3.methylbutanol, no significant increase in the micronucleus frequency was observed at 48 hours after treatment. At 24 hours, no increase was seen in males, whereas a weak increase (1.7 per 1000 cells with micronuclei; negative control: 0.5 per 1000 cells; p<0.02) was seen in females.
No increase was seen for the number of normochromatic cells with micronuclei.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
3-methylbutanol was not genotoxic in-vivo (mouse micronucleus test). The result can be interpolated to isovaleric acid because the alcohol is rapidly oxidised to the acid. - Executive summary:
3-methylbutanol was tested for its potential to induce chromosome damage (micronuclei) in mice. The study was conducted according to OECD 474 using NMRI mice (5 per sex and dose) and under GLP conditions. The animals received 1500 mg 3-methylbutanolkg bw by oral gavage; vehicle and positive controls (cyclophosphamide) were included. The dose was selected based on clear toxicity observed in animals at 2000 mg/kg bw, but not at 1000 mg(kg bw.
Clear signs of toxicity were seen (dyspnea, prone position in 75% of the animals; titubation in 25% of the animals) along with a significant body weight decrease. No increase of micronucleated polychromatic was noted in males and females at 24 and 48 hours after treatment, except a weak, yet statistically significant increase in females at 24 hours (1.7 per 1000 cells with micronuclei; negative control: 0.5 per 1000 cells; p<0.02).No increase was seen for the number of normochromatic cells with micronuclei. The vehicle and positive controls performed as expected. It was thus concluded that 3-methylbutanol did not induce micronuclei in-vivo (Utesch and Walter, 1999).
The study is considered to be valid and the result can be transferred to isovaleric acid since the alcohol is rapidly oxidised to acid in-vivo.
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