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EC number: 407-770-0 | CAS number: 61597-96-4 D(+)-LACTATE D'ISOBUTYLE
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Publication. Study conducted in accordance to OECD guideline 408. 2-methyl-1-propanol was used for read-across to isobutyl-R-lactate.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 997
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- 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
- Reference substance name:
- Isobutanol
- IUPAC Name:
- Isobutanol
- Test material form:
- other: liquid
- Details on test material:
- - Name of test material (as cited in study report): 2-methyl-1-propanol (MEP)
- Purity: 99.8%
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr Thomae GmbH, Biberach/Riss, Germany
- Age at study initiation: 6 weeks
- Weight at study initiation: mean body weight male: 172 g, female: 147 g
- Housing: Individually in stainless steel wire mesh cages (type DK III)
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The drinking water solutions were prepared freshly twice a week. To ensure homogenity of the solutions of the test substance in the drinking water, each mixture was stirred for about 30 min using a magnetic stirrer. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability and homogeneity of the test substance in the drinking water was analysed over a period of 6 days. To check for the applied concentrations a sample of each concentration was taken for analysis by capillary gas chromatography at the beginning and at the end of the application period.
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- ad libitum (as drinking water solutions)
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 1000, 4000, 16000 ppm
Basis:
nominal in water
- Remarks:
- Doses / Concentrations:
0, 80, 340, 1450 mg/kg/d
Basis:
nominal in water
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
Based on the results of of a dose range finding study to check for palatability 16000 ppm was selected as maximum dose to avoid this complication. - Positive control:
- N.A.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: individual body weights were recorded at the beginning of the study and weekly throughout the study.
FOOD CONSUMPTION :
Food consumption were determined once a week
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: once a week for a period of 4 days. The mean daily intake of the test substance (in mg per kg body weight) was calculated at the intervals at which water consumption was determined
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Prior to the beginning of treatment and at the termination of the animals by using an ophthalmoscope.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on day 87 of the study. Blood was taken from the retroorbital venous plexus
- Animals fasted: No data
- How many animals: 10 animals/sex/dose
- Parameters examined were: white blood cells, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, reticulocytes, differential blood count and prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on day 87 of the study. Blood was taken from the retroorbital venous plexus
- Animals fasted: No data
- How many animals: 10 animals/sex/dose
- Parameters examined were: sodium, potassium, chloride, inorganic phosphate, calcium, glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum-glutamyltransferase, urea, albumin, blood creatinine, total bilirubin, total protein, globulins, triglycerides, cholesterol
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
After sacrification, the animals were necropsied and assessed by gross pathology. The weight of the anesthetized animals and the weights of their livers, kidneys, adrenal glands and testes were determined. Organs or tissues required by guidelines as well as gross lesions were fixed in a 4% formaldehyd solution.
HISTOPATHOLOGY: Yes
Histological examinations and assessment of the findings were carried out after histotechnical processing and staining with hematoxylin and eosin. - Other examinations:
- None
- Statistics:
- Mean values and standard deviations were calculated for body weight, food and water consumption, intake of the test substances, hematological and clinical chemistry parameters as well as for absolute and relative organ weights. The organ weights were statistically evaluated using the DUNNETT’s test for comparison of the dose groups with the control groups. The analysis of variance (ANOVA) with subsequent DUNNETT’s test was used to compare the body weights as well as the hematological and clinical biochemistry data of the dose groups with those of the control groups.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No effects on mortality and clinical signs occurred.
- Mortality:
- no mortality observed
- Description (incidence):
- No effects on mortality and clinical signs occurred.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No treatment related effects. Histopathological changes of the testes (tubular degeneration and diffuse hyperplasia of Leydig’s cells), the spleen (minimal increase in extramedullary hematopoiesis) or the kidneys (dilation of the renal pelvis) occurred sporadically in control and/or animals treated with MEP.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 16 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects at highest dose.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1: Effective test substance intake | |||||||
Test group |
MEP concentration in drinking water (p.p.m.) |
Mean daily substance intake (mg/kg bw) | |||||
males | females | ||||||
1 | 1000 | 75 | 91 | ||||
2 | 4000 | 300 | 385 | ||||
3 | 16000 | 1251 | 1657 |
Applicant's summary and conclusion
- Conclusions:
- The NOAEL of 2-methyl-1-propanol after oral administration via the drinking water over a period of 90 days is considered to be 16000 ppm for both sexes.
- Executive summary:
A repeated subchronic oral dose toxicity study (OECD 408) was conducted using male and female Wistar rats at doses of 0, 1000 ppm (about 80 mg/kg/d), 4000 ppm (about 340 mg/kg/d), and 16000 p.p.m. (about 1450 mg/kg/day) of 2-methyl-1-propanol (99.8% purity). The animals received the test item daily over a period of 90 days via the drinking water. The test substance had no effect on mortality, food consumption, water consumption, body weight, haematological and clinical chemistry examinations and on pathological findings. Based on the results reported the NOAEL for orally administered 2-methyl-1-propanol via the drinking water is considered to be 16000 p.p.m. (about 1450 mg/kg bw/day) for both sexes.
This study in rats is acceptable and satisfies the principle requirement for a repeated oral dose toxicity study according to OECD 408 in rats. Due to the fact that isobutanol is a degradation product of isobutyl lactate, this result is relevaant for risk assessment.
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