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EC number: 258-004-5 | CAS number: 52556-42-0
- 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
Description of key information
A 28-days repeated dose toxicity study regarding oral application is available. A NOAEL of 150 mg/kg bw/day is found and no target organ was identified.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 June - 3 October 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: Guideline for Toxicity Testings of New Chemical Substances, Notification No. 1121002 of Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Wlfare, Japan
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: 5 weeks
- Weight at study initiation: 129.3 - 144.9 g (males); 109.0 - 130.3 g (females)
- Fasting period before study:
- Housing: individually; stainless steel wired cages
- Diet: MF, lot No. 070808, Oriental Yeast Co.,Ltd. ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 25 °C
- Humidity (%): 40 to 70 %
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Concentration in vehicle: 10 w/v%, 1.5 w/v%, 0.25 w/v%
- Amount of vehicle (if gavage): 10 mL
- Lot/batch no. (if required): 070719A - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability of the test item and the concentration in the vehicle was determined by IR absorption spectroscopy and High performance liquid chromatography. No changes in the IR spectrum (400 to 4000 cm-1) and in the chromatogram were observed.
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- once daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 25 mg/kg bw/day (nominal)
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: a 7-day repeated-dose oral toxicity study was conducted, indicating the choosen doses
- Rationale for selecting satellite groups: highest concentration and therefore most likly affected group
- Post-exposure recovery period in satellite groups: 14 days - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: three times daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: on day 1, 3, 8, 12, 17, 21, 26, 28 recovery period: day 1, 5, 10, 14
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on day 28 (not recovery group) or day 14 of recovery period
- Anaesthetic used for blood collection: Yes (Ether)
- Animals fasted: Yes
- How many animals: all
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on day 28 (not recovery group) or day 14 of recovery period
- Animals fasted: Yes
- How many animals: all
URINALYSIS: Yes
- Time schedule for collection of urine: on day 28 (not recovery group) or day 14 of recovery period
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
NEUROBEHAVIOURAL EXAMINATION: Yes / No / No data
- Time schedule for examinations: in the last week of the study
- Dose groups that were examined: all
- Battery of functions tested: sensory activity / grip strength / motor activity - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table)
Macroscopic observation of body surface, openings, subcutaneous tissue, cranial cavity, thoracic cavity, abdominal cavity, pelvic cavity and their contents.
HISTOPATHOLOGY:
Trachea and lungs, stomach, intestines, liver, heart, kidneys, bladder, testes, epididymides, prostate, seminal vesicles, ovaries, uterus, vagina, brain, spinal cord, sciatic nerve, bone marrow, lymph nodes, spleen, thymus, pituitary gland, throid gland, adrenal glands, eyeballs - Other examinations:
- measurement of food consumption
- Statistics:
- body weight, food conssumption, hematological findings, blood biochemical findings, urine volume, urine specific gravity, organ weights, grip strength and ultromotivity were examined for equality of variance by the Bartlett method.
If equality of variance was detected at 5 % significance level, one-way layout analysis of variance was performed.
If a significant difference was detected in the analysis of variance, the test by the Dunnett method was perforemd between the vehicle control group and each of the treatment groups.
If there was no equality of variance, the Kruskal-Wallis test was performed.
If a significant difference was detected the nonparametric Dunnett test was perfomed between the vehicle control group and each of the treatment groups.
the frequencies of evacuation and urination were examined by the Krukal-Wallis test.
If a significant difference was detected the nonparametric Dunnett test was perfomed between the vehicle control group and each of the treatment groups. - Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- During the treatment period
No significant change was noted in males or females.
During the recovery period
No significant change was noted in males or females. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- During the treatment period
No significant change was noted in males or females.
During the recovery period
Males: No significant change was noted.
Females: The food consumption increased significantly on Day 4 of recovery in the 1000 mg/kg group. - Ophthalmological findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- effects observed, treatment-related
- 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
- Details on results:
- CLINICAL SIGNS AND MORTALITY
no mortality occured
loose feces in 3 animals treated with 150 mg/kg bw/day, loose feces and salivation in all animals and diarrhea in 10 animals treated with 1000 mg/kg bw/day
BODY WEIGHT AND WEIGHT GAIN
normal
FOOD EFFICIENCY
in the recovery group treated with 1000 mg/kg bw/day the food uptake increased
HAEMATOLOGY
the percentage of basophils decreased significantly in the 1000 mg/kg bw/day female recovery group
CLINICAL CHEMISTRY
high gamma-glutamyl transpeptidase level in the 25 and 150 mg/kg bw/day female groups; high A/Gratio and low creatinine level in the 1000 mg/kg bw/day male recovery group
URINALYSIS
normal
NEUROBEHAVIOUR
amount of ultromotivity decreased at 30 to 40 minutes in the 1000 mg/kg bw/day group
ORGAN WEIGHTS
normal
GROSS PATHOLOGY
bulging of the edge of the anterio stomach in one animal of the 1000 mg/kg bw/day male and female group
nodules of the spleen in one animal of the control male group
shrinkage of the left thyroid lobe in one animal of the 25 mg/kg bw/day male group
swollen spleen in one animal of the 150 mg/kg bw/day male group
uterine cyst in one animal of the 25 mg/kg bw/day female group
HISTOPATHOLOGY: NON-NEOPLASTIC
germinal center differentiation of the spleen in one animal of the control male group
hypoplasia of the left thyroid lobe in one animal of the 25 mg/kg bw/day male group
capsulitisof the spleen in one animal of the 150 mg/kg bw/day male group
hyperplasia of the squamous epithelium at the edge of the anterior stomach in two animal of the 1000 mg/kg bw/day male group
uterine cyst in the muscle layer in one animal of the 25 mg/kg bw/day female group
hyperplasia of the squamous epithelium at the edge of the anterior stomach in three animal of the 1000 mg/kg bw/day female group - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Critical effects observed:
- not specified
- Conclusions:
- The study is well performed and gives following results for the Endpoint:
NOAEL = 150 mg/kg bw/day
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 150 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- only one study available. a 90 day repeated dose toxicity test has been proposed.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
only one study available
Justification for classification or non-classification
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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