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EC number: 480-410-8 | CAS number: 13482-23-0
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
NO(A)EL: 50 mg/kg/day in male rats and 300 mg/kg/day in female rats over a 28-day administration period by gavage.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
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:
- March - Sept 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- 1995
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- other: aqueous 0.5% methylcellulose 400
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- 1 per day
- Remarks:
- Doses / Concentrations:
50, 300 and 1000 mg/kg bw.
Basis:
nominal in diet - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- At 1000 mg/kg/day, increased salivation was observed in all males and females on most days throughout the dosing period. At 300 and 50 mg/kg, there were no treatment-related clinical signs observed during the course of the study.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- not toxicologically relevant
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean absolute and relative liver weights were statistically significantly greater in males and females at 1000 mg/kg/day and in males only at 300 mg/kg/day when compared to controls. These organ weight changes were considered to be attributable to treatment with the test substance.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Enlarged liver was found in all males at 1000 mg/kg/day and in 3/5 males at 300 mg/kg/day.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- In the liver, minimal to moderate midzonal hepatocellular degeneration/necrosis was observed in 4/5 males at 1000 mg/kg/day and in 1/5 males at 300 mg/kg/day. This finding was associated with minimal to slight midzonal to panlobular hepatocellular hypertrophy in 4/5 males at 1000 mg/kg/day and in 2/5 males at 300 mg/kg/day. These changes were considered to be toxicologically relevant in males.
In females, up to the highest dose level tested, there was no evidence of any treatment-related histopathological change. - Key result
- Dose descriptor:
- NOEL
- Effect level:
- 50 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- clinical biochemistry
- gross pathology
- histopathology: non-neoplastic
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- clinical biochemistry
- histopathology: non-neoplastic
- Critical effects observed:
- not specified
- Conclusions:
- Although for the liver findings especially in male rats STOT-RE was considered when applying Haber's rule on equivalent guidance values, based on WoE no classification for STOT-RE is proposed with the following arguments:
1) low severity (minimal) of histopathological findings in the liver of male rats at 300 mg/kg in combination with no findings on liver-specific enzyme parameters in the blood
2) histopathological findings on hypertrophy are regarded as potentially reversible
3) histopathological findings on necrosis are minimal and focal
4) liver enlargement is often observed as an adaptive mechanism due to rat-specific CYP induction
5) increased levels of cholesterol and triglycerides were not dose-dependent - Executive summary:
In conclusion the No Observed (Adverse) Effect Level of the test substance in this study was 50 mg/kg/day in males and 300 mg/kg/day in females over a 28-day administration period by gavage.
Reference
Mortality:
There were no mortalities observed during the course of the study.
Clinical signs:
At 1000 mg/kg/day, increased salivation was observed in all males and females on most days throughout the dosing period. At 300 and 50 mg/kg, there were no treatment-related clinical signs observed during the course of the study.
Body weight:
There was no effect on body weight or body weight gain parameters in either sex.
Food consumption:
Mean food consumption was unaffected by treatment in either sex.
Ophthalmological examination:
No ocular abnormalities were noted at ophthalmological examination.
Neurotoxicity assessment:
Up to the highest dose level tested of 1000 mg/kg/day, there was no evidence of a treatment-related effect on the mean exploratory locomotor activity in either sex. The slight increase in overall mean exploratory locomotor activity noted at 1000 mg/kg/day in both sexes (+23% in males and +21% in females, respectively, not statistically significant) and at 300 mg/kg/day in females (+29%, not statistically significant) were considered not to be treatment-related as the increases were of low magnitude and observed with no dose-relationship.
No treatment-related changes were recorded during the open field observation at any dose level in either sex. Change in gait noted in high dose males was observed in isolation and was therefore considered not to be treatment-related.
All reflexes and responses evaluated were unaffected by the treatment at any dose level in either sex. The changes noted in both sexes were those commonly recorded or were observed with no dose-relationship and were considered not to be treatment-related.
The fore- and hindlimb grip strength were unaffected by the treatment at any dose level in either sex.
Hematology:
No treatment-related change was noted for any of the parameters assayed in the study in either sex. The few differences observed, even if statistically significant, were considered to be incidental and/or not treatment-related.
Clinical Chemistry:
Increased mean total cholesterol concentrations were observed at 1000 mg/kg/day in both sexes (+42% and +35% in males and females, respectively, p<0.01) and at 300 mg/kg/day in males (+31%, p<0.05). At 1000 mg/kg/day mean triglycerides concentration was increased in females (+98%, p<0.01) and total protein and albumin concentrations were elevated in males (+13%, p<0.01).
In the absence of a dose-relation effect, the other statistically significant changes were considered not to be treatment-related.
A tendency towards decreased chloride concentrations was noted at 1000 mg/kg/day in both sexes. These changes were considered to be treatment-related but, in view of their low magnitude (-4% and -2% in males and females, respectively, p<0.01), were considered not to be toxicologically relevant. Other changes were judged to be incidental. No treatment-related change was seen at 50 mg/kg/day.
Urinalysis:
At 1000 mg/kg/day in males and females, mean urinary volumes were slightly greater (+65%, not statistically significant and +84%, p<0.05, respectively) and mean pH values were decreased (-23%, p<0.01 and -16%, p<0.05, respectively) when compared to controls. In males, decreased pH values were associated with a loss of the crystals usually observed in the urine of male rats.
Cellular casts were observed in all males treated at 1000 mg/kg/day, but some similar casts were also noted in one control female. However, the presence of such casts in the urine was not associated with any microscopic histopathological change. Therefore, they were considered to be treatment-related but not toxicologically relevant.
No treatment-related change was noted at 300 and 50 mg/kg/day.
Terminal body weight and organ weight:
There was no relevant change in mean terminal body weights when compared to controls.
Mean absolute and relative liver weights were statistically significantly greater in males and females at 1000 mg/kg/day and in males only at 300 mg/kg/day when compared to controls. These organ weight changes were considered to be attributable to treatment with the test substance. In males, the liver weight changes were dose-related and associated with hepatocellular hypertrophy at microscopic examination. At 1000 mg/kg/day in females, the minimally increased mean absolute liver weight and mean liver to brain weight ratio were not associated with histopathological findings.
All other organ weight differences were judged to be incidental in view of their individual variation.
Gross pathology:
Enlarged liver was found in all males at 1000 mg/kg/day and in 3/5 males at 300 mg/kg/day.
All other changes were considered as incidental and not treatment-related.
Microscopic pathology:
Treatment-related effects were found in the liver in males only. In the liver, minimal to moderate midzonal hepatocellular degeneration/necrosis was observed in 4/5 males at 1000 mg/kg/day and in 1/5 males at 300 mg/kg/day. This finding was associated with minimal to slight midzonal to panlobular hepatocellular hypertrophy in 4/5 males at 1000 mg/kg/day and in 2/5 males at 300 mg/kg/day. These changes were considered to be toxicologically relevant in males. In females, up to the highest dose level tested, there was no evidence of any treatment-related histopathological change.
The other microscopic findings, including the higher incidence of necrotic foci in the liver, were those commonly observed in the rat of this strain and age and were considered to be incidental in origin.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 50 mg/kg bw/day
- Study duration:
- subacute
- Experimental exposure time per week (hours/week):
- 7
- Species:
- rat
- Quality of whole database:
- Klimisch Rel-1
- System:
- gastrointestinal tract
- Organ:
- liver
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
Although for the liver findings especially in male rats STOT-RE was considered when applying Haber's rule on equivalent guidance values, based on WoE no classification for STOT-RE is proposed with the following arguments:
- low severity (minimal) of histopathological findings in the liver of male rats at 300 mg/kg in combination with no findings on liver-specific enzyme parameters in the blood
- histopathological findings on hypertrophy are regarded as potentially reversible
-histopathological findings on necrosis are minimal and focal
-liver enlargement might be an adaptive mechanism due to rat-specific CYP induction
- increased levels of cholesterol and triglycerides were not dose-dependent
Justification for classification or non-classification
Based on WoE and primarily the low severity of histopathological findings in the liver of male rats at 300 mg/kg no classification for STOT-RE is warranted
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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