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EC number: 412-640-1 | CAS number: 84632-50-8
- 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:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1993-02-23 to 1993-08-20
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP compliant Guideline study (OECD Guideline 407 adopted 1981). Main deviations from OECD 407 adopted 2008: no FOB or neurobehavioural examinations, less organs weighed, few organs histopathologically examined.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
- Reference Type:
- other: Amendment Final Report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted May 12, 1981
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Version / remarks:
- adopted Sept. 19, 1984
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 412-640-1
- EC Name:
- -
- Cas Number:
- 84632-50-8
- Molecular formula:
- C20 H10 N4 O2
- IUPAC Name:
- 3-[4-(3-cyanophenyl)-3,6-dioxo-2H,3H,5H,6H-pyrrolo[3,4-c]pyrrol-1-yl]benzonitrile
- Details on test material:
- - Analytical purity: 97%
- Appearance: orange 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: Charles River (UK) Ltd., Margate, Kent, England
- Age at study initiation: 28 ± 1 days (at delivery)
- Weight at study initiation: 64 to 91 g
- Fasting period before study: no
- Housing: in groups of five according to sex in metal cages with wire mesh floors
- Diet: Special Diet Services Rat and Mouse Maintenance Diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 20 days
ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 22°C
- Humidity: 32-62%
- Air changes: approximately 19 per hour
- Photoperiod: 12 hours artificial light (0700 - 1900 hours) in each 24-hour period
IN-LIFE DATES: From: 1993-03-09 To: 1993-04-01 or 1993-04-15 (recovery groups)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
A 10% w/v suspension of test item was prepared freshly each day with 1 % w/v aqueous methylcellulose until a smooth paste was formed.
VEHICLE
- Concentration in vehicle: 1 %
- Amount of vehicle: 10 mL / kg bw / day - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analytical results indicate that the doses were accurately formulated during the toxicity study. The results also confirm that the formulations were homogeneous and stable from the time of preparation to completion of dosing.
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- Daily, seven days per week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 15, 150, 1000 mg / kg bw / day
Basis:
actual ingested
- No. of animals per sex per dose:
- 5 males and 5 females (plus 5 males and 5 females per satellite group: vehicle and high dose)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: rat acute toxicity data and a 7-day preliminary oral toxicity study [HRC Report No.: CBG 583/930621]
- Post-exposure recovery period in satellite groups: 14 days
Examinations
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS: Yes
- Time schedule: at least twice a day
- Observations: checked for signs of ill health, behavioural changes or toxicosis.
BODY WEIGHT: Yes
- Time schedule for examinations: prior to dosing on Day 1 (Week 0) and subsequentiy at weekly intervals
FOOD CONSUMPTION:
- Food consumption for each group of animals determined and mean daily diet consumption calculated as g food/kg body weight/week: Yes (from group mean)
WATER CONSUMPTION: No (visual appraisal only)
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood:
I. on day 30 (all surviving non-recovery group animals)
II. on day 44 (all surviving animals of recovery groups)
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: Yes
- How many animals: I) 40, i.e surviving animals except recovery groups; II) all surviving animals of recovery groups
- Parameters examined: packed cell volume, haemoglobin, red blood cell count, MCHC, MCV, platelet count, total white cell count, differential white blood cell count: neutrophils, lymphocytes, eosinophils, basophils, monocytes. Morphological abnormalities: poly- / hypochromasia, anisocytosis, Rouleaux formation.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: see HAEMATOLOGY
- Animals fasted: Yes
- How many animals: see HAEMATOLOGY
- Parameters examined: glucose, total proteins, albumin, globulin, total globulin minus albumin, albumin/globulin ratio, urea nitrogen, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, total bilirubin, sodium, potassium, chloride, calcium, inorganic phosphorus, cholesterol, triglycerides
URINALYSIS: Yes
- Time schedule for collection of urine: night before blood collection
- Metabolism cages used for collection of urine: not specified
- Animals fasted: Yes
- Parameters examined: volume, pH, specific gravity, proteins, total reducing substances, glucose, ketones, bile pigments, urobilinogen, haem pigments, epithelial cells, polymorphonuclear and mononuclear leucocytes, erythrocytes, organisms, renal tubule casts, sperm, orther abnormal constituents
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (all animals)
adrenals, aorta, brain (medullary, cerebellar, and cortical sections), caecum, colon, duodenum, eyes (Davidson's fluid as fixative), femur (for bone and marrow sections) with joint, Harderian gland, head (to preserve nasal cavity, paranasal sinuses, oral cavity, nasopharynx, middle ear, teeth, lachrymal gland and Zymbal's gland), heart, ileum, jejunum, kidneys, larynx, liver, lungs, lymph nodes (cervical and, mesenteric), mammary glands, oesophagus, ovaries, pancreas, pharynx, pituitary, prostate, rectum, salivary gland, sciatic nerve, seminal vesicles, skeletal muscle, skin, spinal cord (cervical level), spleen, stomach, testes (including epididymis), thymus (where present), thyroid (with parathyroid), tongue, trachea, urinary bladder, uterus, vagina, any macroscopically abnormal tissue
ORGAN WEIGHT (all animals):
adrenals, brain, kidneys, liver, spleen, ovaries, testes (with epididymides)
HISTOPATHOLOGY: Yes
- preserved: all listed under GROSS PATHOLOGY
- Histopathologically examined (vehicle and high dose group, except satellite groups):
adrenals, heart, kidneys, liver, spleen, testes (including epididymis), abnormal tissue - Statistics:
- Significant differences between control animals and those treated with the test substance were expressed at the 5% (* P<0.05) or 1% (** P<0.01) level.
Bodyweight gains, organ weight and clinical pathology data: Fisher's exact test followed by Mantel's test for a trend in proportions, otherwise Bartlett's test for heterogeneity of variance between treatments. Logarithmic transformation if significant heterogeneity was found at the 1 % level. If distribution homoscedastic, ANOVA followed by Williams' test for dose-related response. If distribution heteroscedastic, Kruskal-Wallis analysis followed by Shirley's test.
Covariate analysis: if data correlations at the 10% level of significance, data adjustments (with final bodyweight as covariate).
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY
No treatment-related clinical signs were noted and there were no mortalities.
BODY WEIGHT AND WEIGHT GAIN
There were no statistically significant differences in bodyweight or bodyweight gains between treated and control rats.
FOOD CONSUMPTION
There was no obvious difference in food consumption between treated and control rats.
OPHTHALMOSCOPIC EXAMINATION
Not examined
HAEMATOLOGY
There were no differences between treated and control rats that were considered to be test item related.
CLINICAL CHEMISTRY
There were no differences between treated and control rats that were considered to be test item related.
URINALYSIS
There were no differences between treated and control rats that were considered to be test item related.
NEUROBEHAVIOUR
Not examined
ORGAN WEIGHTS
There were no differences between treated and control rats that were considered to be test item related.
GROSS PATHOLOGY
No tteatment-related changes were observed in the terminal or recovery groups.
HISTOPATHOLOGY
No treatment-related changes were observed in the tissues examined at termination. The minor/incidental changes observed are considered to be of no toxicological importance.
HISTORICAL CONTROL DATA: not specified
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Lack of test item related toxic effects at all dosages applied, incl. limit dose.
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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