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EC number: 459-270-7 | CAS number: 2568-33-4 MBD
- 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:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 8 June 2005 - 20 October 2005
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: OPPTS 870.3050, Repeated Dose 28-Day Oral Toxicity Study in Rodents, July 2000. .
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 3-methyl-1,3-butandiol
- EC Number:
- 459-270-7
- EC Name:
- 3-methyl-1,3-butandiol
- Cas Number:
- 2568-33-4
- Molecular formula:
- C5 H12 O2
- IUPAC Name:
- 3-methylbutane-1,3-diol
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- Description: A clear colourless liquid
Storage conditions: Room temperature in the dark
Lot number: 52834
Expiry date: December 2006
Purity: >98%
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD
- Details on species / strain selection:
- (SD)IGS BR rats
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Age at study initiation: 45 to 49 days
- Weight at study initiation: 221.3 to 257.3 g for males and 158.8 to 190.1 g for females.
- Fasting period before study: overnight before routine blood sampling
- Housing:The cages were made of a stainless steel body with a stainless steel mesh lid and floor
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): freely available
- Acclimation period: 12 days
- Environmental enrichment: chew block
DETAILS OF FOOD AND WATER QUALITY:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air changes (per hr): passed to atmosphere and not re-circulated
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours continuous dark per 24 hours
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- Animals received the test substance or vehicle control formulations orally using a suitably graduated syringe and a rubber catheter (Ch 8) inserted via the mouth into the stomach.
- Vehicle:
- water
- Remarks:
- for formulation
- Details on oral exposure:
- Method of administration:
Gavage - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Gas liquid chromatograph (GLC)
A representative sample of test formulation was accurately weighed and dissolved in a suitable volume of acetone. The extract was diluted using acetone to provide a solution containing the test item at an expected concentration in the range 40 µg/ml - 80 µg/ml.
- Linearity was confirmed over the nominal concentration range 20 µg/ml – 100 µg/ml with a coefficient of determination >0.995.
- The precision of injection was <5% for six replicate injections of standard solutions containing the test ietm at nominal concentrations of 20 µg/ml and 100 µg/ml
- Mean procedural recovery value of 94.0% (CV=5.89%, n=6) was obtained for 1 mg/ml and 99.9% (CV=2.47%, n=6) was obtained for 100 mg/ml.
- limit of detection: 0.12 mg/ml - Duration of treatment / exposure:
- Test duration: 28 days
- Frequency of treatment:
- Dosing regime: 7 days/week
- No. of animals per sex per dose:
- Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day - Details on study design:
- Administration
Observations: Clinical, Detailed physical examination and arena observations, Neurobehavioural screening, Sensory reactivity, Bodyweight, Motor activity, Food consumption, Haematology
Necropsy: after 4 weeks of treatment
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Before treatment commenced and during each week of treatment
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: Day -7, Day 1, weekly throughout the treatment, Day 28, before necropsy
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 29 of treatment
- Anaesthetic used for blood collection: Yes general anaesthesia
- Animals fasted: Yes
- How many animals: all animals
- Parameters checked in 'List of parameters checked for Haematology' were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Day 29 of treatment
- Animals fasted: Yes
- How many animals: all animals
- Parameters checked in 'List of parameters checked for Clinical chemistry' were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: During Week 4 of treatmen
- Dose groups that were examined: each group
- Battery of functions tested: sensory activity / grip strength / motor activity / Touch response / Auditory startle response / Tail pinch response - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes:
Adrenals Liver
Brain Ovaries
Epididymides (Epididymid) Spleen
Heart Testes
Kidneys Thymus
HISTOPATHOLOGY: Yes - Statistics:
- All statistical analyses were carried out separately for males and females.
All analyses were carried out using the individual animal as the basic experimental unit.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No treatment related clinical signs were observed throughout the study.
- Mortality:
- no mortality observed
- Description (incidence):
- No unscheduled deaths were observed throughout the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Overall group mean bodyweight gains for all treated groups were similar to controls.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Food consumption values for all treated groups were similar to control throughout the study
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- Overall group mean food conversion efficiency values for all treated groups were similar to controls.
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Group mean APTT values were statistically significantly lower than controls for all treated groups, however as the individual values for each group were within the expected background range for animals of this age and strain (APTT rat: ♂ 1 percentile 11.6, mean
19.76, 99 percentile 28.5, ♀ 1 percentile 8.5, mean 16.49, 99 percentile 24.3), there was no dose relationship for the females and no treatment-related histopathology findings, this finding is considered not to be of toxicological importance.
There were no other differences from controls, which were considered possibly associated with treatment. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A higher than control group mean albumin value was recorded for females receiving 1000 mg/kg/day accompanied by a higher than control A/G ratio. These effects of treatment were not supported by any histopathological or other corroborative findings from the study and thus were considered not to be of toxicological importance.
A higher than control group mean sodium value was recorded for females receiving 150 mg/kg/day, however as the sodium values for females treated at 1000 mg/kg/day were comparable with controls, this finding is considered not to be treatment-related.
There were no other differences from controls, which were considered possibly associated with treatment. - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Absolute adrenal and thymus weights were higher than controls for males receiving 1000 mg/kg/day, however there were no corresponding macroscopic or microscopic changes. Bodyweight adjusted kidney weights were statistically significantly higher than controls for
females receiving 150 or 1000 mg/kg/day, however as no dosage relationship was observed and there were no corresponding macroscopic or microscopic findings this finding is considered not to be treatment-related.
There were no other differences from controls, which were considered possibly associated with treatment. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- The macroscopic examination performed at termination revealed no changes attributable to treatment with the test item.
Testes:
Seminiferous tubules were evaluated with respect to their stage in the spermatogenic cycle and the integrity of the various cell types present within the different stages. No cell or stage specific abnormalities were noted. - Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Details on results:
- Clinical observations:
No unscheduled deaths, treatment related clinical or neurobehavioral signs were observed throughout the study.
Overall group mean bodyweight gains, food consumption values and food conversion efficiency for all treated groups were similar to controls.
Laboratory findings:
Group mean APTT values were lower than controls (Range:M:15- 18% + F:12-23%) for all teated groups. However, as the individual values were within the background data range,there was no dose-relationship for the females and no
treatment-related histopathology findings, this finding is considered not to be of toxicological importance.
A higher than control mean albumin value was recorded for females receiving 1000 mg/kg/day accompanied by a higher than control A/G ratio. These effects of treatment were not supported by any histopathological or other corroborative findings from the study and thus were not considered to be of toxicological importance.
Effects in organs:
Absolute adrenal and thymus weights were higher than controls for males receiving 1000 mg/kg/day.
The macroscopic and microscopic examinations performed at termination revealed no changes in attributable to treatment.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- food efficiency
- gross pathology
- haematology
- mortality
- organ weights and organ / body weight ratios
- Key result
- Dose descriptor:
- NOEL
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- food efficiency
- gross pathology
- haematology
- mortality
- organ weights and organ / body weight ratios
- Remarks on result:
- not determinable
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- System:
- other: all
- Organ:
- other: none
Applicant's summary and conclusion
- Conclusions:
- It is concluded that oral administration of MBD to rats for four weeks did not result in any findings of toxicological importance. Therefore 1000 mg/kg/day is regarded as the highest No Observed Adverse Effect Level (NOAEL) on this study.
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