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EC number: 404-110-3 | 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
Description of key information
No adverse treatment-related effects were observed in a reliable subacute oral rat study at daily doses up to 1000 mg/kg bw/day. No studies after repeated dermal or inhalation exposure are available.
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:
- From 30 Mar to 27 Apr 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study (OECD TG 407), according to GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- (adopted 1981)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: HOECHST AG, Kastengrund, Germany
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: males: mean 123 - 125 g; females: mean 115 - 122
- Fasting period before study: no
- Housing: groups of 5 per sex
- Diet (ad libitum): Altromin 1324 rat diet (Altromin GmbH, Lage/Lippe, Germany)
- Water (ad libitum): tap water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): not stated, fully air-conditioned
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- other: 2% starch mucilage
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: daily
VEHICLE
- Justification for use and choice of vehicle (if other than water): test item not soluble in water
- Concentration in vehicle: 0, 1.25, 5, 20 % (w/v)
- Amount of vehicle (if gavage): 5 mL/Kg bw - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
- Remarks:
- Doses / Concentrations:
0, 62.5, 250, 1000 mg/kg bw
Basis:
actual ingested - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: after single application of 2000 mg/kg bw of the test item to rats no animal died within the 14 d observation period and no clinical signs of toxicity were observed; based on these findings the doses for the subacute toxicity study were selected
- Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: behaviour and general health status at least daily (twice daily during work days and once daily during weekend and at holidays); weekly check neurological disturbances, eye opacity, damage of oral mucosa and impairment of dental growth
- Cage side observations not reported in detail.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: before treatment and 2 times per week during exposure period
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes (measurement 2 times per week)
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
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: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: weekly; water consumption over 16 h was determined weekly
OPHTHALMOSCOPIC EXAMINATION: Yes (turbidity)
- Time schedule for examinations: weekly
- Dose groups that were examined: all
HAEMATOLOGY: Yes
- Time schedule for collection of blood: before final sacrifice
- Anaesthetic used for blood collection: Yes (nembutal)
- Animals fasted: No
- How many animals: all
- Parameters examined: erythrocytes count, haemoglobin, haematocrit, leucocytes count, thrombocytes count, differential blood count, reticulocytes (only control and high dose group), Heinz bodies (only control and high dose group), mean clotting time, MCV, MCH, MCHC
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: before final sacrifice
- Animals fasted: No
- How many animals: all
- Parameters examined: sodium, potassium, inorganic phosphorus, uric acid, total bilirubin, creatinine, glucose, urea, calcium, chloride, GOT, GPT, alkaline phosphatase, gamma glutamyl transpeptidase, total protein, albumin and globulin
URINALYSIS: Yes
- Time schedule for collection of urine: overnight from day 26 to 27 of the study
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters examined: appearance, colour, pH, hemoglobin, protein, glucose, ketone bodies, bilirubin, urobilinogen, specific gravity, sediment (only control and high dose group)
NEUROBEHAVIOURAL EXAMINATION: No
OTHER:
- organ weights: heart, lung, liver, kidney, spleen, testes, adrenals - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (heart, lung, liver, kidney, spleen, stomach, jejunum, colon, thymus, testes, adrenals, bone marrow (femur)) - Statistics:
- Body weights at the designated measurement times, haematological data, clinical chemistry parameters, absolute organ weights and organ to body weight ratios, pH and specific gravity of urine were evaluated with the aid of a pro- gram package for the evaluation of toxicological studies, according to the respective standard operating procedures.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- 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:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- no adverse effects
- faeces was discoloured blue from day 6 of the experiment in the mid and high dose group
- no compound-related neurological disturbances, opacity of the refracting media of the eyes, impairment of dental growth or changes of the oral mucosa were observed
BODY WEIGHT AND WEIGHT GAIN
- no effects
FOOD CONSUMPTION
- no effects
FOOD EFFICIENCY
- not examined
WATER CONSUMPTION
- no effects
OPHTHALMOSCOPIC EXAMINATION
- no effects
HAEMATOLOGY
- no adverse effects
- mean clotting time was statistically significant increased in males of the mid dose group, but all values were within the range of the historical controls and no such effect observed in other dose groups or in females
CLINICAL CHEMISTRY-
- no adverse effects
- statistically significant decrease of bilirubin concentration in females of high dose group; this effect was not regarded to be meaningful as only an increase would be toxicologically relevant
- statistically significant increased alpha-1 globulin and decreased albumin and albumin/globulin ratio in males of the high dose group; these effects were not regarded to be relevant by the authors of the study as there were no correlating histopathological or clinical findings
URINALYSIS
- no effects
NEUROBEHAVIOUR
- not examined
ORGAN WEIGHTS
- no adverse effects
- statistically signifcant increased relative (but not absolute) lung weights in males of the high dose group (0.475 +/- 0.062; 0.535 +/- 0.069; 0.466 +/- 0.042; 0.597 +/- 0.096 % body weight in the control, low, mid, high dose group respectively); no such effect occurred in females, no histopathological findings, therefore the effects were not regarded to be of toxicological relevance
GROSS PATHOLOGY
-no effects
HISTOPATHOLOGY: NON-NEOPLASTIC
- no adverse effects
- only incidential observations - Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed up to the highest dose tested
- Critical effects observed:
- not specified
- Conclusions:
- Under the conditions of this study the test item did not induce adverse treatment related effects after 28 days of exposure to doses up to 1000 mg/kg bw/d.
- Executive summary:
Groups of 5 male and 5 female Wistar rats received the test item in a subacute study according to OECD guideline 407 and GLP by oral gavage at dose levels of 0, 62.5, 250 or 1000 mg/kg body weight per day for 28 days and were necropsied at day 29. There were no clinical signs or mortality. Blue discolouring of the faeces occurred in males and females of the mid and high dose group starting on day six of treatment. Behaviour, health status, body weight development, food and water consumption were not impaired in males and females of all groups. Clinical chemistry revealed a statistically significant decrease of bilirubin concentration in females of high dose group. This effect was not regarded to be meaningful as only an increase would be toxicologically relevant. A statistically significant increase of alpha-1 globulin and a decrease of albumin and albumin/globulin ratio was observed in males of the high dose group. These effects were not regarded to be relevant as there were no correlating histopathological or clinical findings. The haematological examinations did not reveal any substance related changes except statistically significant increase of the mean clotting time in males of the mid dose group. As all values were within the range of the historical controls and no such effect was observed in other dose groups or in females they were not regarded to be of any relevance. No treatment-related changes were detected by urinalysis. The administration of the test compound did not affect absolute or relative organ weights except of the lung weights in males. The absolute and and relative lung weights were increased in males of the high dose group. But only the effect on relative lung weights revealed statistical significance. As there were no histopathological correlations and no such effects occurred in female rats the effects were judged not to be of toxicological relevance. No compound-related macroscopically visible changes were found at necropsy. The histopathological examinations also revealed no substance-related changes. Under the conditions of this study the test item did not produce adverse treatment related effects after 28 days of exposure to doses up to 1000 mg/kg bw/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Reliable NOAEL from a subacute toxicity study
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- This information is not available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- This information is not available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- This information is not available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- This information is not available
Additional information
Oral exposure:
In a reliable subacute oral rat study (Hoechst, 1989, RL 1) no treatment-related adverse were observed at daily doses up to 1000 mg/kg bw/day, including all examination parameters requested by the guideline. The study was performed in accordance with the OECD TG 407 adopted 1981. In comparison to the acutal OECD TG 407 (adopted 3 October 2008) it has to be stated that no detailed clinical observations and no neurobehavioural investigations were performed and that organ weights and histopathological investigations of some organs recommended in the actual guideline are missing. But, taking into account that there were no indications of substance related adverse effects it is concluded that the study can be regarded as valid for the evaluation of the subacute oral toxicity of the submission substance.
Inhalation exposure:
No study available
Dermal exposure:
No study available
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Guideline study (OECD TG 407), according to GLP
Justification for classification or non-classification
Based on the available reliable data the test substance has not to be classified for repeated dose toxicity according to Regulation (EC) No 1272/2008 and Council Directive 67/548/EEC.
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