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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 201-195-7 | CAS number: 79-31-2
- 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
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: comparable to guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2-methylpropan-1-ol
- EC Number:
- 201-148-0
- EC Name:
- 2-methylpropan-1-ol
- Cas Number:
- 78-83-1
- Molecular formula:
- C4H10O
- IUPAC Name:
- 2-methylpropan-1-ol
- Details on test material:
- - Name of test material (as cited in study report): 2-methyl-1-propanol, MEP
- Analytical purity: 99.8%
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: no data
- Stability under test conditions: yes
- Storage condition of test material: no data
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- Himalayan
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Thomae GmbH, Biberach/Riss, Germany
- Age at study initiation: 24 - 29 weeks
- Weight at study initiation: 2.5 - 2.7 kg
- Fasting period before study: no data
- Housing: individually in wire-mesh cages, type K 300/8 (EBECO, Becker and Co., Castrop Rauxel, Germany), air conditioned rooms
- Diet (e.g. ad libitum): KLIBA rabbit laboratory diet 24-341-4, 10 mm pellets (Klingentalmühle AG, Kaiseraugst, Switzerland)
- Water (e.g. ad libitum): tap water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 /12
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: horizontal-flow whole-body exposure chamber (glas/steel construction, volume 1.1.m³ (BASF AG, Ludwigshafen, Germany)
- Method of holding animals in test chamber: individually in wire cages
- Source and rate of air: clean air
- Method of conditioning air: no data
- System of generating particulates/aerosols: evaporator maintained at 50-70°C, TS was delivered by a continuously operating pump
- Temperature, humidity, pressure in air chamber: 21-24°C, 49-64%, minimal negative pressure
- Air flow rate: 275 L/minute
- Air change rate: 15 air changes per hour
- Method of particle size determination: no particle size determination
- Treatment of exhaust air: no data
TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography (Hewlett-Packard GC, Model 5840 A with FID detector)
- Samples taken from breathing zone: no data - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of the inhalation atmosphere were analyzed hourly during exposure.
Mean concentrations ± SD measured in inhalation chamber: 0.50 ± 0.010 mg/L, 2.51 ± 0.091 mg/L, 10.00 ± 0.370 mg/L - Details on mating procedure:
- - Impregnation procedure: artificial insemination
- Verification of same strain and source of both sexes: no data
- Proof of pregnancy: day of insemination referred to as day 0 of pregnancy, the following day was defined as day 1 of pregnancy or postinsemination (pi) respectively - Duration of treatment / exposure:
- day 7 - 19 of pregnancy (pi)
- Frequency of treatment:
- 6 hours / day
- Duration of test:
- 29 days
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0.5; 2.5; 10 mg/L
Basis:
nominal conc.
- No. of animals per sex per dose:
- 15 female rabbits per group
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Dose selection rationale: preliminary range-finding study
- Rationale for animal assignment (if not random): random
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule:
BODY WEIGHT: Yes
- Time schedule for examinations: day 0, 3, 7, an from then on at 3-day intervals until day 29
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29 by intravenous application of pentobarbitone
- Organs examined: uterus and ovaries
OTHER: Yes
- gross pathology for all animals - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter; fixation in Bouin's solution according to the method of Barrow and Taylor (1969)
- Skeletal examinations: Yes: all per litter; fixation in ethyl acohol and staining according to a modified method of Dawson (1926)
- Head examinations: Yes: No data - Statistics:
- The Dunnett test (Dunnett, 1955, 1964) was used to statistically compare body weight, body weight changes, the number of corpora lutea, implants, resorptions, live fetuses, and pre- or postimplantation losses. The Fisher's exact test (Dixon, 1981) was used for evaluating the conception rate, maternal mortality, and all fetal findings.
- Historical control data:
- Historical control data were used to further evaluate findings of uncertain relevance.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
One rabbit of the 0.5 mg/L group was killed on day 21 of gestation due to abortion. One rabbit exposed to 2.5 mg/L was found dead on day 24 of gestation. Both cases were considered not to be related to isobutanol inhalation.
10 mg/L group
Slight retardation of body weight gain of the dams, especially during the first of the exposure periods.
Indication of an irritant eye effect (reddish, lid closure, slight discharge)
2.5 mg/L and 0.5 mg/L group
no substance-related effects were observed.
Gross-pathologiy examination revealed no effects that could be attributed to the exposure with isobutanol.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 2.5 mg/L air
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
All treatment groups
The fetuses did not showed any substance-related effects (no indications of any embryo-/fetotoxicity or any teratogenic effect).
The uterine weights of the treated animals were not significantly different from the controls. Compound related effects occured neither for conception rate, mean number of corpora lutea, and implantation sites nor in the values calculated for the pre- and postimplantation loss and the number of resorptions as well as viable fetuses.
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/L air
- Basis for effect level:
- other: fetotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/L air
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/L air
- 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
Table 1 Data on Reproduction, Maternal Body Weight Change and Uterine Weight
Dose [mg/L] |
||||
0 (sham) |
0.5 |
2.5 |
10.0 |
|
Number of animals |
15 |
15 |
15 |
15 |
Number of dams (pregnant animals) |
15 |
15 |
14a,b |
14a |
Corpora lutea/dam |
8.4 |
8.6 |
7.7 |
7.6 |
Implants/dam |
7.5 |
6.7 |
6.5 |
7.0 |
Live fetuses/dam |
7.0 (1.20) |
6.2 (1.72) |
6.0 (2.20) |
7.1 (1.32) |
Dead implants/dam |
0.5 |
0.5 |
0.5 |
0.4 |
Sex ratio (male / female |
48.6 / 51.4 |
51.7 / 48.3 |
44.9 / 55.1 |
50.0 / 50.0 |
Mean fetal weight [g] |
39.0 (3.74) |
39.7 (4.01) |
41.0 (3.46) |
39.4 (1.61) |
Mean placental weight [g] |
4.3 (0.48) |
4.6 (0.56) |
4.8* (0.66) |
4.4 (0.40) |
Mean corrected maternal body weight change [g] ** |
-71.9 (65.77) |
-45.3 (63.91) |
-47.1 (41.43) |
-67.0 (77.51) |
Intact uterine weight [g] |
367.0 (52.48) |
329.3 (69.99) |
330.1 (110.81) |
344.3 (111.43) |
Numbers in parentheses indicate standard deviations
* significantly different from control, p < 0.05
** corrected maternal body weight change = (body weight on day 20 of pregnancy) - (body weight on day 6 of pregnancy) - (uterine weight)a one not pregnant animalb one animal aborted
Table 2 Fetal Anomalies
Dose [mg/L] |
||||
0 (sham) |
0.5 |
2.5 |
10 |
|
Number of litters evaluated |
15 |
14 |
13 |
13 |
Number of fetuses evaluated |
105 |
87 |
78 |
92 |
Total fetal external malformations |
||||
Fetal incidence |
0 |
0 |
0 |
0 |
Litter incidence |
0 |
0 |
0 |
0 |
Total fetal soft tissue malformation |
||||
Fetal incidence |
0 |
0 |
0 |
0 |
Litter incidence |
0 |
0 |
0 |
0 |
Total fetal soft tissue variations |
||||
Fetal incidence |
21 (20.0) |
13 (14.9) |
17 (21.8) |
30 (32.6) |
Litter incidence |
11 (73.3) |
9 (64.3) |
7 (53.8) |
12 (92.3) |
Total fetal skeletal malformations |
||||
Fetal incidence |
2 (1.9) |
1 (1.1) |
0 |
1 (1.1) |
Litter incidence |
2 (13.3) |
1 (7.1) |
0 |
1 (7.7) |
Total fetal skeletal variations |
||||
Fetal incidence |
9 (8.6) |
14 (16.1) |
8 (10.3) |
16 (17.4) |
Litter incidence |
5 (33.3) |
10 (71.4) |
5 (38.5) |
8 (61.5) |
Numbers in parentheses indicate percentage of fetuses/litters affected
* significantly different from control; p < 0.05
** significantly different from control; p < 0.01
The examination of external changes showed no malformations or variations.
For fetal soft tissue no malformations were observed.
Variations were seen in all groups including controls. An increased incidence of separated origin of carotids in the 10 mg/L group was statistically significant (p < 0.01). But historical control data showed that the incidence of fetuses showing this variation was in the range of biological variation. The significantly increased occurence of this variation at the highest concentration was therefore assessed to be incidental.
The skeletal examination revealed various malformations of the sternebrae and/or the vertrebral column. Variations seen in skull, the vertrebal column, the sternum and the ribs were found in all groups without apparent concentration relationships or statistically significant differences between the groups.
Any observed differences between groups were within the range of biological variation and/or occurred without a clear concentration dependency.
Applicant's summary and conclusion
- Conclusions:
- A slight maternal toxicity was seen at the highest exposure (10 mg/L, borderline concentration) in this inhalation study. No signs of developmental toxicity or teratogenicity were noted even with the highest exposure concentration.
- Executive summary:
The developmental toxicity of isobutanol (purity 99.8%) was tested in an inhalation study in pregnant Himalayan rabbits. 15 female animals were exposed to vapors of isobutanol at concentrations of 0, 0.5, 2.5 and 10 mg/L for 6 hours/day from day 7 through 19 of gestation. All animals were killed on day 29 of gestation. The fetuses were removed and examined for compound-related effects.
In the high concentration exposure group (10 mg/L) retardation in body weight change was observed especially during the first phase of the exposure. This is an indication of maternal toxicity. The exposure to 10 mg/L seems to be a borderline concentration for causing maternal toxicity. Thus the maternal NOAEL is 2.5 mg/L .
The fetuses did not exhibit any signs of treatment-related embryo-/fetotoxicity or teratogenic effects at all exposure levels. The developmental NOAEL is 10 mg/L.
(Klimisch 1990).
This inhalation developmental toxicity study in the rabbit is classified acceptable and satisfies the guideline requirements for a developmental toxicity study (OECD 414).
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.