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EC number: 440-240-7 | CAS number: 1282554-35-1
- 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
- Study period:
- 2012
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Test procedure in accordance with national standard methods (China) with acceptable restrictions.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: Section 4 of the Guidelines for the Testing of Chemicals: Health Effects (ministry of environmental protection of People´s Republic of China)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2-Propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)benzimidazole
- IUPAC Name:
- 2-Propyl-4-methyl-6-(1-methylbenzimidazole-2-yl)benzimidazole
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: Shanghai SLAC Laboratory Animal Co., Ltd.- Weight at study initiation: 116 to 130g- Housing: every two animals were kept in a polycarbonate box, which was disinfected with an autoclave; boxes were changed twice every week- Diet (e.g. ad libitum): no data- Water (e.g. ad libitum): ad libitum- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20°C to 25°C- Humidity (%): 40 to 70%- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 1% CMC-Na
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- once daily (volume 5 mL/kg bw)
Doses / concentrations
- Remarks:
- Doses / Concentrations:250, 50, 10 mg/kg bw/dBasis:
- No. of animals per sex per dose:
- 10
- Control animals:
- other: yes
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No dataDETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: daily (dermahemia, bruise, fluffy fur, ophthalmoptosis, blood discharge, slow breathing, rapid breathing, ached back, cahexia, unusual cry, physical agitation, unusual posture, limpness, jumping, mast tail, tremors, spasm, convulsion, unbalanced movement, retard reaction, hyper-reflexia, diarrhea, anorexia, pupil dilation, pupil reduction, salivating, tearing, dirty perineum, urine incontinence, death)BODY WEIGHT: Yes - Time schedule for examinations: weeklyFOOD EFFICIENCY: food consumption weeklyWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): NoOPHTHALMOSCOPIC EXAMINATION: NoHAEMATOLOGY: Yes - Time schedule for collection of blood: at the end of the test- How many animals: all- Parameters checked: red blood cell, hemoglobin content, white blood cell, differential leukocyte count, platelet counts, plasma prothrombin and activated partial thromboplatinCLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: at the end of the test- How many animals: all- Parameters checked: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase total protein, albumin, bilirubin total, blood urea nitrogen, creatinine, cholinesterase, cholesterol total, glucose, Na, K, Cl, Ca and P ions.URINALYSIS: Yes - Time schedule for collection of urine: at the end of the test- Parameters checked: specific gravity, pH, protein contents, blood/blood cells and glucose concentrationsNEUROBEHAVIOURAL EXAMINATION: No
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes HISTOPATHOLOGY: Yes (brain, heart, lung, liver, thymus, spleen, kidney, adrenal gland, testis or ovary, nervus ischiadicus, cervical, spinal cord, thyroid, stomach, duodenum, jejunum, ileum, colon, rectum, mesenteric lymph node, prostate, epididymides, urinary bladder and uterus)
- Statistics:
- ANOVA, t-test
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- 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:
- additional high dose males/females = additional group tested with 250 mg/kg bw/d with additional 14-day recovery periodadditional control group males/females = additional control group with additional 14-day recovery periodCLINICAL SIGNS AND MORTALITYNo obvious clinical signs or death in any group during the whole experimental periodBODY WEIGHT AND WEIGHT GAINThere were significant decreases of body weights of males of high dose group from 2nd to 13th week. The body weights of the additional high dose males (250 mg/kg bw/d with additional 14-day recovery period) were significantly decreased from 2nd to 15th week.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)FOOD EFFICIENCYThere were significant decreases of total food efficiency of males of high dose group from 2nd to 13th week. The total feed efficiency of the additional high dose females (250 mg/kg bw/d with additional 14-day recovery period) was significantly decreased. The total feed efficiency of the additional high dose males (250 mg/kg bw/d with additional 14-day recovery period) was significantly decreased from 2nd to 15th week.WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)OPHTHALMOSCOPIC EXAMINATIONHAEMATOLOGYA significant decrease of WBC in females of high dose group was noted. Furthermore, values of RBC in females of additional high dose group were significantly decreased. Despite the statistical differences, these changes were not clinically meaningful.CLINICAL CHEMISTRYOn serum biochemical examination, values of CHOL, K, Ca and P in high dose females were significantly decreased, and values of Ca in mid dose females were significantly increased. Values of Ca and P were significantly increased and values of TP were significantly decreased in high dose males. Values of ALB were significantly decreased in additional high dose females and values of ALT, AST and K were significantly decreased in additional high dose males.URINALYSISThere was no abnormality of the specific gravity, color, pH, glucose, crypt-blood and protein contain.NEUROBEHAVIOURORGAN WEIGHTSA significant increase in absolute weights of kidneys and relative organ weights of heart, liver, spleen and kidneys in high dose females were noted. Significant increases in relative organ weights of lung and kidneys in high dose males and a significant increase in relative organ weight of lung in mid dose (50 mg/kg bw/d) males were noted. The relative organ weights of brain, spleen, lung, kidneys and testes in additional high dose males (250 mg/kg bw/d with 14-day recovery period) were significantly increased while absolute weights of heart, liver and adrenal glands were significantly decreased. There was a significant increase in absolute weights of adrenal glands in additional high dose females.GROSS PATHOLOGYUneven appearance of the kidneys of high dose animals and additional high dose animals was noted during macroscopical observation.HISTOPATHOLOGY: NON-NEOPLASTICThe histopathological results under optic microscope were described as follows:Control group (10 female animals): no overt abnormalities.High dose group (10 female animals): light-grade hydropic degeneration/ negrosis of the renal tubule epithelium with light grade interstitial inflammatory cell infiltration in one case; mid-grade hydropic degeneration/necrosis of the renal tubule epithelium with mid-grade interstitial inflammatory cell infiltration in 3 cases; light-grade hydropic degeneration of the renal tubule epithelium in 4 cases; light-grade hydropic degeneration of the renal tubule epithelium with light-grade interstitial inflammatory cell infiltration in 1 case; mid-grade hydropic degeneration/necrosis of the renal tubule epithelium, mid-grade renal tubular dilatation and light-grade renal tubular cast with light-grade interstitial inflammatory cell infiltration in 1 case.Control group (10 male animals): focal necrosis of the myocardial cells with light-grade infiltration of inflammatory cells in the subepicardial layer in 1 case; light-grade hepatocyte fatty degeneration in 3 cases; mid-grade hepatocyte fatty degeneration in 1 case; light-grade infiltration of inflammatory cells of interstitial tissue of prostate in 3 cases.High dosage group (10 male animals): focal necrosis of the myocardial cells with light-grade infiltration of inflammatory cells in the subepicardial layer in 1 case ; light –grade hepatocyte fatty degeneration in 3 cases; mid-grade hepatocyte fatty degeneration in 1 case; light-grade hydropic degeneration of the renal tubule epithelium in 2 cases; mid-grade hydropic degeneration of the renal tubule epithelium in 2 cases; light-grade hydropic degeneration/necrosis of the renal tubule epithelium in 1 case, light-grade infiltration of inflammatory cells of interstitial tissue of prostate in 3 cases Mid dosage group (10 female animals): light-grade hydropic degeneration of the renal tubule epithelium in 2 cases; mid-grade hydropic degeneration of the renal tubule epithelium in 1 case.Mid dosage group (10 male animals): light-grade hydropic degeneration of the renal tubule epithelium in 3 cases.Low dosage group (10 female animals): light-grade infiltration of inflammatory cells beneath the mucosa of the pelvis in 1 case.Low dosage group (10 male animals): no overt abnormalities.Additional control group (10 female animals): no overt abnormalities.Additional high dosage group (10 female animals): mid-grade hydropic degeneration/necrosis of the renal tubule epithelium with mid-grade interstitial inflammatory cell infiltration and light-grade dilatation of collecting tube in the renal papillae in 1 case; light-grade hydropic degeneration/necrosis of the renal tubule epithelium with light-grade interstitial inflammatory cell infiltration in 2 case; light-grade hydropic degeneration/necrosis of the renal tubule epithelium with mid-grade interstitial inflammatory cell infiltration in 2 cases, mid-grade hydropic degeneration/necrosis of the renal tubule epithelium with mid-grade interstitial inflammatory cell infiltration in 2 cases; light grade hydropic degeneration of the renal tubule epithelium in 2 cases.Additional control group (10 male animals): light-grade hepatocyte fatty degeneration in 3 cases; mid-grade hepatocyte fatty degeneration in 1 case: light –grade infiltration of inflammatory cells of interstitial tissue of prostate in 3 cases.Additional high dosage group (10 male animals): light-grade hepatocyte fatty degeneration in 2 cases; light-grade hydropic degeneration/necrosis of the renal tubule epithelium with light-grade interstitial inflammatory cell infiltration in 1 case; high-grade hydropic degeneration/necrosis of the renal tubule epithelium and light-grade renal tubular cast with high-grade interstitial inflammatory cell infiltration in 1 case; high-grade hydropic degeneration/necrosis of the renal tubule epithelium with high-grade interstitial inflammatory cell infiltration and mid-grade renal tubular dilatation in 1 case; mid-grade hydropic degeneration/necrosis of the renal tubule epithelium with mid-grade interstitial inflammatory cell infiltration in 3 cases; mid-grade hydropic degeneration/necrosis of the renal tubule epithelium and mid-grade renal tubular cast with mid-grade interstitial inflammatory cell infiltration in 1 case.HISTOPATHOLOGY: NEOPLASTIC (if applicable)HISTORICAL CONTROL DATA (if applicable)OTHER FINDINGS
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effectsbody weight; food efficiency; clinical chemistry; gross pathology; organ weights; histopathology;
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The no observed adverse effect level (NOAEL) of the substance is considered to be 10 mg/kg bw/d for rats under the conditions of this study.
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