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EC number: 230-237-7 | CAS number: 6976-37-0
- 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
The systemic toxicity of the test substance was investigated in an experimental study according to OECD test guideline 422 under GLP-conditions. The substance, solved in distilled water, was administered to Wistar rats of both sexes by oral gavage in doses of 100, 300 and 1000 mg/kg bw daily for 55 to 67 days. Observing mortality, clinical signs, body weight, body weight gain, food consumption, hematology, blood coagulation and clinical chemistry parameters, macroscopic alterations, organ weights and histopathological alterations, no treatment-related toxicological effects were found. Therefore, the substance was considered to be not systemically toxic.
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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- version of 29 July 2016
- Deviations:
- yes
- Remarks:
- minor, without any effect on study results and validity
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No. of test material: Product no. B4429, Lot no. SLBK5235V
- Expiration date of the lot/batch: 30 April 2018
- Purity test date: na
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no - Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Strain: Hsd.Han (of Wistar origin)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Toxi-Coop Zrt., 1103 Budapest, Cserkesz u. 90
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 13 weeks (both sexes)
- Weight at study initiation: males: 359-434g
females: 209-250g
- Fasting period before study: no
- Housing: before mating: 2 animals of the same sex/cage; mating: 1 male and 1 female/cage; pregnant females: individually; males after mating: 2/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 27 days
DETAILS OF FOOD AND WATER QUALITY: food: ssniff SM R/M-Z+H complete diet, changed weekly; tap water, fresh every day
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3°c
- Humidity (%): 30-70%
- Air changes (per hr): 10/hour
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- distilled
- Details on oral exposure:
- - PREPARATION OF DOSING SOLUTIONS:
the substance was solved in distilled water in concentrations of 20, 60 and 200 mg/L
- VEHICLE
- Justification for use and choice of vehicle (if other than water): not applicable
- Concentration in vehicle: 20, 60 and 200 mg/L
- Amount of vehicle (if gavage): 5 mL/kg body weight
- Batch no. (if required): 1610-5527; 1701-5524; 1702-5502 (supplied by Parma Produkt Kft., Budapest, Hungary) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability and homogeneity in distilled water over the range of relevant concentration has been demostrated at room temperature for at least five days (approx. 100%), i.e. the maximum age of solutions administered.
- Duration of treatment / exposure:
- 55-67 days (depending on mating effectiveness)
- Frequency of treatment:
- daily
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 12 male and 12 female per dose and control
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on findings from a 14-day dose-range finding experiment that used the same concentrations
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: not applicable
- Post-exposure recovery period in satellite groups: not applicable
- Section schedule rationale (if not random): random - Positive control:
- none
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: not further specified
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly (starting on Day 0)
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): not applicable
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: Yes (body weight gain only)
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): not applicable
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: appro., 16 hours after last treatment (food deprived)
- Anaesthetic used for blood collection: Yes (isofluran)
- Animals fasted: Yes (approx. 16 hours)
- How many animals: 5 males and 5 females per group (randomly selected)
- Parameters examined:
- white blood cell (leukocyte) count (WBC)
- red blood cell (erythrocyte) count (RBC)
- hemoglobin concentration (HGB)
- hematocrit (HCT)
- platelet (thrombocyte) count (PLT)
- reticulocytes (RET)
- differential white blood cell count
- activated partial thromboplastin time (APTT)
- prothrombin time (PT)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: approx. 16 hours after last treatment (food deprived)
- Animals fasted: Yes (approx. 16 hours)
- How many animals: 5 males and 5 females per group (randomly selected)
- Parameters examined:
- alanine aminotransferase activity (ALT)
- aspartate aminotransferase activity (AST)
- total bilirubin concentration (TBIL)
- creatinine concentration (CREA)
- glucose concentration (GLUC)
- cholesterol concentration (CHOL)
- total bilirubin concentration (TBIL)
- bile acids (BAC)
- sodium concentration (Na+)
- potassium concentration (K+)
- albumin concentration (ALB)
- total protein concentration (TPROT)
- T4 (in parental males at termination day 55)
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No
OTHER: none - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- adrenal glands
- bone with bone marrow and joint (femur)
- brain (representative regions: cerebrum, cerebellum, pons and medulla oblongata)
- eyes (lachrymal gland with Harderian glands)
- female mammary gland
- gonads (testis with epididymides, ovaries, uterus with fallopian tube and vagina)
- gross lesions
- heart
- large intestines (caecum, colon, rectum, incl. Peyer's patches)
- liver
- lungs (with main stem bronchi)
- muscle (quadriceps)
- esophagus
- pancreas
- pituitary
- prostate
- salivary glands (submandibular)
- sciatic nerve
- seminal vesicle with coagulating gland
- skin
- small intestines (representative regions: duodenum, ileum, jejunum)
- spinal cord (at three levels: cervical, mid-thoracic and lumber
- spleen
- sternum
- stomach
- thymus
- thyroid + parathyroid
- trachea
- urinary bladder
HISTOPATHOLOGY : Yes (control and high dose group)
- ovaries
- uterus
- vagina
- testes
- epididymides
- prostate
- seminal vesicle with coagulating gland
- thymus (one male inlow dose group due to hemorrhage - Other examinations:
- organ weights:
- brain
- testes
- epididymides
- prostate
- seminal vesicle with coagulating gland - Statistics:
- Depending on variance homogeneity between groups (Bartlett's test), parametric or non-parametric (Kruskal-Wallis test) ANOVA was performed, with subsequent inter-group comparisons (Duncan multiple range test or Mann-Whitney U-Test) in case of significant ANOVA results. If applicable, the Chi-square test was performed.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- In the 300 mg/kg bw dose group, brownish fur around the right eye of one male rat and alopecia on the chest of one female rat were observed. These findings occur sporadically in experimental rats and were not related to the treatment.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Some sporadic statistically differences in some parameters (lower mean percentage of monocytes and basophil granulocytes, and a higher mean percentage of reticulocytes at 100 mg/kg bw/day; higher mean percentage of reticulocytes at 300 mg/kg bw/day; lower mean percentage of neutrophil granulocytes and a higher mean percentage of lymphocytes at 1000 mg/kg bw/day) were not related to dose and considered of no toxicological relevance.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Some sporadic statistically differences in some parameters (higher mean sodium concentration at 100 mg/kg bw/day; elevated urea concentrations at 300 mg/kg bw/day (females) and elevated glucose concentrations at all doses (female)) were not related to dose and considered of no toxicological relevance.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Some sporadic statistically differences in some parameters (reduced mean weights of adrenal glands (absolute and relative organ weights) in males at all treatment doses; lower brain and heart weights relative to body weight at 300 mg/kg bw/day (males)) were not related to dose and considered of no toxicological relevance.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Findings were only present in single rats of both sexes in all groups including control, such as pale and smaller seminal vesicle (1 male of control), thymic hemorrhage (one male at 100 mg/kg bw/day and one female at 1000 mg/kg bw/day), slight hydrometra (1 female at 100 mg/kg bw/day, 2 females at 300 mg/kg bw/day, 1 female at 1000 mg/kg bw/day). In the absence of corresponding histopathological findings and a dose relation, these were considered to be not toxicologically relevant.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Histopathological examinations did not reveal any test item related alterations in the organs or tissues of male and female rat at 1000 mg/kg bw/day (ovaries, uterus, vagina, testes, epididymides, prostate and seminal vesicles with coagulation gland in all animals; full histopathology in selected animals).
In one control male a decreased amount of secretum in the seminal vesicle (one side) was observed, which was considered as an individual disorder without toxicological significance.
In the other male rats, the investigated organs of the reproductive system were histologically normal. The various spermatogenic cells were the same in quantity and morphologically in the testes of controls and treated groups. Histology of the epididymides, seminal vesicles and coagulating glands was normal in all animals.
In the female rat the investigated organs of the reproductive system were histologically normal. The cortical region of the ovaries contained primary, secondary and tertiary follicles and corpora lutea, indicating active maturation of oocytes, and ovulation Also the epithelial capsule and ovarian stroma was normal in all cases.
Some lesions were noted (dilatation of uterine horns of one female at 1000 mg/kg bw/day; pulmonary alveolar emphysema in two males and 2 females of the control and two males at 1000 mg/kg bw/day; alveolar histicytosis in one control male; hyperplasia of bronchus associated lymphoid tissue in one control female and two females at 1000 mg/kg bw/day; acute hemorrhage in the thymus in one male at 100 mg/kg bw/day and one female at 1000 mg/kg bw/day) .
Pulmonary emphysema and acute hemorrhage were considered as a consequence of hypoxia, dyspnea and circulatory disturbance developed during exsanguination procedure. Alveolar histicytosis is a common incidental findings in elder rat. Hyperplasia of bronchus associated lymphoid tissue is a physiological immune-morphological phenomenon without toxicological significance. Dilatation of the uterine horns is indicative of a slight neuro-hormonal phenomenon and is in connection with the normal sexual cycle (pro-estrous phase) of uterus without pathological significance. - Histopathological findings: neoplastic:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Critical effects observed:
- no
- Executive summary:
The systemic toxicity of the test substance was investigated in a experimental study according to OECD test guideline 422 under GLP-conditions. The substance, solved in distilled water, was administered to Wistar rats of both sexes by oral gavage in doses of 100, 300 and 1000 mg/kg bw daily for 55 to 67 days. Observing mortality, clinical signs, body weight, body weight gain, food consumption, hematology, blood coagulation and clinical chemistry parameters, macroscopic alterations, organ weights and histopathological alterations, no treatment-related toxicological effects were found. Therefore, the substance was considered to be not systemically toxic in this study.
Reference
The systemic toxicity of the test substance was investigated in a experimental study according to OECD test guideline 422 under GLP-conditions. The substance, solved in distilled water, was administered to Wistar rats of both sexes by oral gavage in doses of 100, 300 and 1000 mg/kg bw daily for 55 to 67 days. Observing mortality, clinical signs, body weight, body weight gain, food consumption, hematology, blood coagulation and clinical chemistry parameters, macroscopic alterations, organ weights and histopathological alterations, no treatment-related toxicological effects were found. Therefore, the substance was considered to be not systemically toxic in this study.
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:
- The only available study is of high quality.
Additional information
Justification for classification or non-classification
Due to the absence of any systemic toxicity in the available data, the substance does not need to be classified for systemic effects.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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