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EC number: 939-200-6 | CAS number: -
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Reproductive effects observed:
- not specified
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No studies are available on the reproductive toxicity of the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate. Histopathological changes in reproductive organs in repeated dose toxicity studies are indicative of effects on fertility. In this respect, repeated dose toxicity studies should be considered to be sensitive and provide sufficient information to evaluate toxicity on fertility if histological examination of the reproductive organs is covered.
Based on available datasets and chemical and structural considerations, read across from the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate to repeated dose and developmental toxicity studies on isobutanol and isobutyl isobutyrate is appropriate to address the REACH Annex VII-IX data requirements and to provide a characterisation of the reproductive hazard of the substance. No effects on reproductive parameters where seen in rats 90-day repeated dose toxicity studies using isobutanol and isobutyl isobutyrate respectively. No effects on reproductive parameters were seen in pre-natal developmental toxicity studies conducted using rats and rabbits. Isobutanol is not a reproductive toxicant – no affects on reproductive parameters were seen in a two-generation inhalation reproductive toxicity study at the highest dose tested (7580 mg/m3). On this basis, the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate is not predicted to be a reproductive toxicant.
Short description of key information:
No studies are available on the reproductive toxicity of Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate. No evidence of an effect on the reproductive organs was seen in repeated dose toxicity studies or developmental toxicity studies using the read-across substances isobutanol and isobutyl isobutyrate. On this basis, the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate is not predicted to be a reproductive toxicant. In this respect, repeated dose toxicity studies should be considered sensitive and sufficient information to evaluate toxicity on fertility if histological examination of the reproductive organs is covered.
Effects on developmental toxicity
Description of key information
Based on existing datasets and structural and chemical considerations, read-across from the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate to available developmental toxicity studies on isobutanol is appropriate to meet the REACH Annex VII-IX data requirements. While rabbit dams were more sensitive to treatment than rats, no effects were seem on developmental parameters in pre-natal developmental toxicity studies in which rats or rabbits were exposed to isobutanol at concentrations up to 10,000 mg/m3 (i.e. the highest dose tested).
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Not reported
- Reliability:
- 2 (reliable with restrictions)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- Fifteen female rabbits per group were exposed to 2-Methyl-1-propanol vapours at concentrations of 10, 2.5, or 0.5 mg/L, 6 hr/day. The rabbits were exposed on Days 7 -19 postinsemination . Control groups were exposed to clean air. The body weights of the animals were determined several times throughout the studies. All rabbits were killed on Day 29 postinsemination. The foetuses were removed from the uterus and examined for compound-related effects.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rabbit
- Strain:
- Himalayan
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. K. 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: None
- Housing: Individually in wire cages
- Diet (e.g. ad libitum): KLIBA rabbit laboratory diet ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported
IN-LIFE DATES: From: Not reported To: Not reported - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- clean air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Horizontal-flow whole-body exposure chamber
- Method of holding animals in test chamber: Not reported
- Source and rate of air: Not reported
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: Concentrations were achieved by supplying the test substances via continuously operating pumps to evaporators maintained at 50-70°C by a water circulation thermostat.
- Temperature, humidity, pressure in air chamber: Supply and exhaust air flows were adjusted by flow meters, in order to achieve a minimal negative pressure in the inhalation chamgers. Temperature was 21-24°C amd relative humidity was 49-60%
- Air flow rate: 15 air exchanges per hour
- Air change rate: 15 air exchanges per hour
- Method of particle size determination: Not reported
- Treatment of exhaust air: Not reported
TEST ATMOSPHERE
- Brief description of analytical method used: Samples of inhalation atmospheres were analysed houly by gas chromatography.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of inhalation atmospheres were analysed houly by gas chromatography.
- Details on mating procedure:
- The rabbits were fertilized by artificial insemination; the day of insemination was defined as Day 0 and the following day was defined as Day 1 postinsemination
- Duration of treatment / exposure:
- Daily for 6 hours/day from days 7 - 19 postinsemination.
- Frequency of treatment:
- Daily for 6 hours/day
- Duration of test:
- After termination of the exposure period, the rabbits were observed up to Day 29 postinsemination.
- Remarks:
- Doses / Concentrations:
0.5, 2.5, 10 mg/L, 6 hr/day
Basis:
nominal conc. - No. of animals per sex per dose:
- 15 females/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No further data on dosing rationale.
The animals were randomly allocated to the test groups. - Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: state of health
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 3 and 7 and from then on at 3-day intervals until Day 29 postinsemination
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 Day 29 postinsemination
- Organs examined: Uterus and ovaries were removed for the following delerminations: intact uterine weight, number of corpom lutea, and number of
implants, the latter being differentiated into live fetuses and dead implants (early and late resorptions, dead fetuses). The pre- and postimplantation losses were calculated. - 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
- Skeletal examinations: Yes: all per litter
- Head examinations: No data - Statistics:
- The Dunnett test was used to statistically compare body weight, body weight changes, corrected body weight gain, intact uterine weight, fetal and placental weights, the number of corpora lutea. implants, resorptions, live fetuses, and pre- or postimplantat ion losses. The Fisher's exact test was used for evaluating the conception rate, maternal mortality, and all fetal findings.
- Indices:
- No further data
- Historical control data:
- No further data
- Details on maternal toxic effects:
- Maternal toxic effects:yes. Remark: slight maternal toxic effects at the highest dose (10 mg/L) of 2-Methyl-1-propanol
Details on maternal toxic effects:
Only slight maternal toxic effects were induced in Himalayan rabbits after exposure to 10 mg/L of 2-Methyl-1-propanol - Dose descriptor:
- NOAEL
- Effect level:
- ca. 2.5 mg/L air
- Based on:
- other: 2-Methyl-1-propanol
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- > 10 mg/L air
- Based on:
- other: 2-Methyl-1-propanol
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No treatment related effects. All effects were concidered incidental and were within the normal variations for the species. - Dose descriptor:
- NOAEL
- Effect level:
- > 10 mg/L air
- Based on:
- other: 2-Methyl-1-propanol
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- NOAEL
- Effect level:
- > 10 mg/L air
- Based on:
- other: 2-Methyl-1-propanol
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- > 10 mg/L air
- Based on:
- other: 2-Methyl-1-propanol
- Basis for effect level:
- other: fetotoxicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- The highest concentration of 10 mg/L appeared to be a borderline concentration for causing maternal toxicity. 2.5 mg/L was therefore the NOAEL after exposure to 2-Methyl-1-propanol.
The highest concentration level of 10 mg/L was found to be a clear NOAEL for the fetal organisms. - Executive summary:
Fifteen female rabbits per group were exposed to 2-Methyl-1-propanol (isobutanol) vapours at concentrations of 10, 2.5, or 0.5 mg/L, 6 hr/day. The rabbits were exposed on Days 7 -19 postinsemination. Control groups were exposed to clean air. The body weights of the animals were determined several times throughout the studies. All rabbits were killed on Day 29 postinsemination. The foetuses were removed from the uterus and examined for compound-related effects. The high concentration of 10 mg/L caused a slight retardation of body weight gain in the dams exposed to 2-Methyl-1-propanol during the first days of the exposure period.. The foetuses exhibited no signs of embryotoxicity, fetotoxicity or teratogenicity effects caused by 2-Methyl-1-propanol. Under the experimental conditions, 2.5 mg/L was found to be a no-observable-adverse-effect level (NOAEL) for the dams exposed to 2-Methyl-1-propanol. For both substances 10 mg/L was defined as the NOAEL for the conceptuses.
Reference
No further data
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 10 000 mg/m³
- Study duration:
- subchronic
- Species:
- rabbit
- Quality of whole database:
- Klimisch score = 2. The key study is an acceptable, well documented prenatal developmental toxicity study which meets scientific principles and is therefore reliable for the determination of the sub-chronic endpoint.
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No studies on the developmental toxicity of the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate are available. Read-across from the substance to developmental toxicity studies on isobutanol is appropriate to meet the REACH Annex VII-IX data requirements.Read-across is scientifically justified and also enables the REACH requirements to be adequately addressed, while avoiding unnecessary animal testing in accordance with EU Directive 86/609/EEC.
The potential for isobutanol to cause developmental toxicity was investigated in two definitive inhalation studies conducted according to OECD Test Guideline 414 using rats and rabbits respectively (Klimisch and Hellwig, 1995). In the studies, groups of pregnant female rats (25/group) or rabbits (15/group) were exposed via inhalation to isobutanol at concentrations of 0, 500, 2,500 or 10,000 mg/m3(0, 151, 758, or 3030 ppm, respectively) for 6 hours/day during gestation (rats - days 6-15; rabbits – days 7-19). Rabbit dams exposed to 10,000 mg/m3had slight decreases in body weight gain during gestation while exposures in rats had no treatment-related effects. No evidence of developmental or fetotoxicity was reported in either the rats or the rabbits. The NOAEL for developmental toxicity in rats and rabbits was considered to be 10,000 mg/m3, i.e. the highest dose tested.
Justification for selection of Effect on developmental toxicity: via inhalation route:
Based on existing datasets and structural and chemical considerations, read-across from the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate to available developmental toxicity studies on isobutanol is appropriate to meet the REACH Annex VII-IX data requirements. While rabbit dams were more sensitive to treatment than rats, no effects were seem on developmental parameters in pre-natal developmental toxicity studies in which rats or rabbits were exposed to isobutanol at concentrations up to 10,000 mg/m3 (i.e. the highest dose tested).
Justification for classification or non-classification
Based on read-across to developmental toxicity studies in rats and rabbits conducted using isobutanol, the Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate is not predicted to be a developmental toxicant.The substance does not meet the criteria for classification for developmental toxicity according to Directive 67/548/EEC or Regulation 1272/2008/EC.
Additional information
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.
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