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EC number: - | 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
A 7-day oral toxicity study (Carcia and Alumà, 2008) is available which is key study. The LOAEL was considered to be less than 150 mg/kg bw/day.
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 21 to 28 January 2008
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study run to a reliable method and to GLP
- Qualifier:
- according to guideline
- Guideline:
- other: Repeated Dose Toxicity. CPMP/SWP/1042/99. 27 July 2000
- Deviations:
- no
- 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: Harlan Interfauna Ibérica, S.L.
- Age at study initiation: Approximately 9 weeks
- Weight at study initiation: Males: 226-242 g Females: 151-169 g
- Fasting period before study:
- Housing: Groups of five rats at the most of the same sex during acclimatization and groups of three rats of the same sex from the same treatment group during treatment in Makrolon type-5 cages with sawdust bedding
- Diet (e.g. ad libitum): Pelleted, standard dry rodent diet, access ad libitum
- Water (e.g. ad libitum): Community tap water was offered to the animals ad libitum in bottles
- Acclimation period: 16 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25℃
- Humidity (%): 30-60%
- Air changes (per hr): More than 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light (7:00 am to 7:00 pm)/12 hours dark (7:00 pm to 7:00 am)
IN-LIFE DATES: From: 21 January 2008 To: 28 January 2008 - Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:
VEHICLE
- Justification for use and choice of vehicle (if other than water): The vehicle was chosen based on the information in Study B65992 (Acute Oral Toxicity Study in Rats) performed in Harlan Laboratories Ltd.
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Lot/batch no. (if required): 2057KMR
- Purity: - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 7 days
- Frequency of treatment:
- Once daily
- Remarks:
- Doses / Concentrations:
0, 150, 300 mg/kg/day
Basis:
actual ingested - No. of animals per sex per dose:
- 3 males and 3 females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
- Rationale for animal assignment (if not random):
- Rationale for selecting satellite groups:
- Post-exposure recovery period in satellite groups:
- Section schedule rationale (if not random): - Positive control:
- None stated
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
Viability/mortality: Twice daily
Clinical signs: Cage-side clinical observations once daily during acclimatization.Three times on test day 1 and at least twice daily on days 2-7.
Food consumption: Once during acclimatization and on days 1 and 7.
Body weights: Once during acclimatization, at days 1, 3 and 7 during the treatment period (immediately before the administration), and before sacrifice.
- Time schedule: Once daily during acclamatization
- Cage side observations checked in table [No.?] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:
BODY WEIGHT: Yes
- Time schedule for examinations:
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day:
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data:
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
A full autopsy was performed on all animals. The autopsy included the examination of the external surface of the body, all orifices, cranial, thoracic and abdominal cavities and the observation of the organs both in situ and after evisceration.
HISTOPATHOLOGY: Yes
adrenal glands, aorta, bone marrow , brain-incluing sections of medulla/pons, cerebral and cerebellar cortex, ovaries, pancreas, rectum, prostate gland and seminal vesicles, skin, spinal cord-cervical, midthoracic - Statistics:
- The following statistical methods were used to analyze the body weight, food consumption, clinical laboratory, organ weights, all ratios and macroscopic findings:
The Dunnett-test (many to one t-test) based on a pooled variance estimate was applied if the variables can be assumed to follow a normal distribution for the comparison of the treated groups and the control groups for each sex.
The Steel-test (many-one rank test) was applied instead of the Dunnett-test when the data can not be assumed to follow a normal distribution.
Fisher's exact-test was applied to the macroscopic findings. - Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Clinical signs and mortality:
In all test item treated groups, muscular hypotonus, hunched back, abnormal gait and ruffled fur were recorded. Three animals (1 male + 2 females) from group 4 died. These deaths were treatment-related.
Body weight and weight gain:
A decrease in body weight and body-weight gain was observed in males from group 3 and 4 and in females from groups 2, 3 and 4. This decrease was dose-related.
Food consumption and compound intake (if feeding study):
A lower dose-related food consumption was recorded in all test item treated groups, with the exception of males from group 2 in which the food consumption was similar to Control group.
Haematology:
A dose-related increase in red blood cells, hemoglobin and hematocrit and a decrease in reticulocyte count was recorded in all test item treated groups in comparison to the Control group.
Clinical chemistry:
In males from group 4 and females from group 3 lower values of creatinine and higher values of proteins and globulin or albumin were recorded in comparison to Control group.
Organ weights: Animals from all groups treated with the test item showed a dose-related decrease of absolute and relative weight of the thymus and spleen.
Histopathology: non-neoplastic:
There were histopathological changes in the heart, spleen, thymus and adrenal glands. - Dose descriptor:
- LOAEL
- Effect level:
- <= 150 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Critical effects observed:
- not specified
- Conclusions:
- The LOAEL was considered to be less than 150 mg/kg bw/day.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LOAEL
- 150 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- 2 (reliable with restrictions)
Additional information
A 7-day oral toxicity study was conducted using rats (Carcia and Alumà, 2008). Key study.
The LOAEL was considered to be less than 150 mg/kg bw/day.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
This study was conducted according to a reliable method under GLP.
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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