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EC number: 613-099-6 | CAS number: 62889-66-1
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Details on test material:
- - Physical state: liquid
- Batch No.: Batch 704 / tank 328 from July 5, 1990
- Storage condition of test material: at a cool place (+4°C)
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr . Karl Thomae GmbH, 7950 Biberach/Riss, Germany
- Age at study initiation: 42 days
- Weight at study initiation: male animals: 180 (166 - 192) g; female animals : 142 (134 - 155) g
- Housing: singly in type DK III stainless steel wire cages from Becker & Co., 4620 Castrop-Rauxel, Germany
- Diet: ad libitum Kliba rats/mice/hamsters maintenance diet, 343 meal, Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland
- Water: e.g. ad libitum
- Acclimation period: 9 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on oral exposure:
- Administration volume: 5 ml/kg bw
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
25, 100, 300 mg/kg bw
Basis:
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice a day (Monday to Friday) and once a day (Saturdays, Sundays and public holidays).
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: The general state of health of the animals was checked twice a day (Monday to Friday) and once a day (Saturdays, Sundays and public holidays).
BODY WEIGHT: Yes
- Time schedule for examinations: on day 0 of the study and once a week thereafter.
FOOD CONSUMPTION AND COMPOUND INTAKE :
- The food consumption over a period of 7 days was determined weekly and calculated as mean food consumption in grams per animal and day.
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: 14 days (erroneously not at the beginning of the study) and 90 days after the beginning of the study
- Dose groups that were examined: Control group and 300 mg/kg bw /day test group
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 29 and 85 days after the start of the administration period
- Anaesthetic used for blood collection: No
- Animals fasted: No
- Parameters checked: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 29 and 85 days after the start of the administration period
- Animals fasted: No
- Parameters checked:
Enzymes: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase,serum-gamma-glutamyltransferase
Blood chemistry: sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, globulins, triglycerides, cholesterol, magnesium - Sacrifice and pathology:
- - animals were fasted 16-20 h prior to sacrifice
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Organs examined: Brain, Pituitary Gland, Thyroid and Parathyroid Glands, Thymus, Trachea, Lungs, Heart, Aorta, Salivary Glands (Mandibular & Sublingual), Liver, Spleen, Kidneys, Adrenal Glands, Pancreas, Testes, Ovaries, Uterus, Oesophagus, Stomach (Forestomach and Glandular Region), Duodenum, Jejunum, Ileum, Caecum, Colon, Rectum, Urinary, Bladder, Mesenteric Lymph Node, Sciatic Nerve, Sternum with Marrow, Femoral Bone Marrow - Statistics:
- Statistical significance were determined by analysis of variance (ANOVA) followed by a DUNNETT's test
Results and discussion
Results of examinations
- Details on results:
- In the lowest dose group (25 mg/kg bw) no substance related effects in any of the endpoints assessed were observed.
MORTALITY
Four animals died or were sacrificed before the end of the treatment period; two control males and two females given the highest dosage. The death of one of the controls was due to accidental trauma inflicted with the gavage. Although no cause of death was established for the other decedents there was no histopathological evidence to indicate that the two females given the highest dosage had died as a result of the administration of the test compound.
CLINICAL SIGNS
-100 mg/ kg bw group: no substance related changes
-300 mg/ kg bw group:
All male and females showed salivation, predominantly after test substance administration. Genital region smeared with urine in 9 male and 10 female animals.
BODY WEIGHT:
-100 mg/ kg bw group: There was a statistically significant (p ≤ 0.05) increase in the body weight of males between day 56 and day 84 (max + 9.1 %), however this difference was statistically not significant at day of sacrifice.
-300 mg/ kg bw group: A statistically significant reduction of terminal body weight of males (10.4 % reduction; p ≤ 0.05).
FOOD CONSUMPTION AND COMPOUND INTAKE:
-100 mg/ kg bw group: no substance related changes
-300 mg/ kg bw group: food consumption was of females was statistically significantly increased at the end of the study (+18% on day 91; p ≤ 0.01), but there was no corresponding effect seen in the body weight.
OPHTHALMOSCOPIC EXAMINATION
-No substance related effect in any group
HAEMATOLOGY
-100 mg/ kg bw group: no substance related changes
-300 mg/ kg bw group: increase of polymorphonuclear neutrophiles (8% females, 74% males; statistically not significant). This increase in polymorphonuclear neutroptphils is treatment-related and might be due to the changes seen in the forestomach of these animals (see histology)
CLINICAL CHEMISTRY
-100 mg/ kg bw group: no substance related changes
-300 mg/ kg bw group:
In males alkaline phosphatase was statistically significant increased (32% ; p ≤ 0.01 ) at day 29 but not at the end of the study
alanine aminotransferase was statistically significant increased in both sexes (55% females, 68% males; p ≤ 0.01)
cholesterol was statistically significant decreased in both sexes (24% females, 36% males; p ≤ 0.01)
ORGAN WEIGHTS
-100 mg/ kg bw group: no substance related changes
-300 mg/ kg bw group:
Statistically significant increased absolute (+21.7%) and relative liver weights (+23.7%) of females (p ≤ 0.01)
Statistically significant increased relative weights of the kidneys (8.3% females, 13.6% males; p ≤ 0.05)
Statistically significant increased relative weights of the adrenal glands (20.9% females, 21% males; p ≤ 0.05 )
Statistically significant increased absolute adrenal weights in females (19.9%; p ≤ 0.05)
HISTOPATHOLOGY
-100 mg/ kg bw group (effects in males only):
Stomach: slight or moderate focal thickening of the forestomach wall, diffuse hyperplasia of the keratinised epithelium, focal epithelial hyperplasia.
-300 mg/ kg bw group:
Stomach: Both sexes had have slight or moderate focal thickening of the forestomach wall, afocal or diffuse hyperplasia of the keratinised epithelium of the forestomach; in few animals hyperkeratosis, submucosal inflammation, submucosal oedema, oedema of the lamina propria and focal ulceration or erosion.
Liver: The amount of fat within centriacinar hepatocytes of males was less than in controls. This change may have resulted from lower calorific intake rather than a direct effect of the test compound since bodyweight was lower in males given the highest dosage than in controls.
Adrenal Glands: Two females had a marked or moderate focal cortical necrosis with fibrosis and mineralisation and a further female from this group had slight cortical fibrosis. No such changes were noted in any of the other animals on study. It is possible that all three lesions had a similar pathogenesis, possibly infarction. However, since these changes can occur spontaneously in rats, the low incidence was considered insufficient to provide clear evidence of a treatment-related effect.
OTHER DEVIATIONS
Some differences in clinicochemical statistically significant inter-group the results of the hematological and clinicochemical examinations. These deviations are marginal, inconsistent,sporadic or lacking dosage-relationship. Accordingly, these changes are considered to be of no toxicological significance.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 25 mg/kg bw/day (actual dose received)
- Sex:
- male
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Sex:
- female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
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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