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EC number: 242-828-7 | CAS number: 19125-99-6
- 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:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data is from HPVIS database
Data source
Reference
- Reference Type:
- secondary source
- Title:
- Repeated dose toxicity for CAS 550-77-4
- Author:
- U.S Environmental Protection agency
- Year:
- 2 017
- Bibliographic source:
- High Production Volume Information System (HPVIS)
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- Repeated dose toxicity study was carried out for substance 2-methyl-1H-isoindole-1,3(2H)-dione on rats.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- N-methylphthalimide
- EC Number:
- 208-982-4
- EC Name:
- N-methylphthalimide
- Cas Number:
- 550-44-7
- Molecular formula:
- C9H7NO2
- IUPAC Name:
- 2-methyl-1H-isoindole-1,3(2H)-dione
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: basal diet
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 30 days
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 other: mg/kg bw/day
- Dose / conc.:
- 250 other: mg/kg bw/day
- Dose / conc.:
- 500 other: mg/kg bw/day
- Dose / conc.:
- 1 000 other: mg/kg bw/day
- No. of animals per sex per dose:
- 0 rats/sex
- Control animals:
- yes
- Details on study design:
- Not specified
- Positive control:
- Not specified
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
- Time schedule:
- 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):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
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: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:
OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:
HAEMATOLOGY: No data
- Time schedule for collection of blood:
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals:
- Parameters checked in table [No.?] were examined.
CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood:
- Animals fasted: No data
- How many animals:
- Parameters checked in table [No.?] were examined.
URINALYSIS: No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined.
NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- Not specified
- Statistics:
- The following statistical tests were utilized to evaluate body weight changes, total food consumption and organ weights: Bartlett's test for homogeneity of variance and one-way classification analysis of variance. If the ANOVA was heterogeneous, a log10 transformation was performed, followed by Bartlett's test. If the log10 transformation was ineffective in removing variance heterogeneity, ANOVA of the untransformed data was completed. When the ANOVA indicated homogeneous data, the Scheffe multiple comparison procedure was used to compare the control and treatment group means. When the ANOVA indicated heterogeneous data, Games and Howell's modification of the Tukey-Kramer honestly signific ant difference test was used to compare the group means.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No significant effects observed.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- One male rat in the 0.25% group died on Day 26 of the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significant decreases in body weight of both male and female rats in the 0.5 and 1.0% groups (6% and 18% lower than controls for males and 4% and 11% lower than control for females, respectively) were noted during the fourth week of exposure.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Mean food consumption values of the treated male and female rats were lower than control at some measurement periods, but the food consumption value for the male rats in the 1.0% group during the final week of exposure was the only statistically significant decrease noted. Mean compound consumption for the male rats in the 0.25, 0.50 and 1.0% groups ranged from 146 to 203 mg/kg/day, 330 to 403 mg/kg/day and 685 to 815 mg/kg/day, respectively. The mean compound consumption for the female rats in the 0.25, 0.5 and 1.0% groups range from 197 to 226 mg/kg/day, 409 to 573 mg/kg/day and 921 to 1100 mg/kg/day, respectively.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean liver relative to terminal body weight was increased for both sexes and mean kidney weight relative to terminal body weight was increased for males at 1.0%.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The gross pathology revealed no treatment-related effects in any PI-treated group.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Microscopic evaluation revealed compound-related findings of centrilobular to diffuse hepatocellular enlargement in rats of both sexes in the 0.5 and 1.0% treatment groups. In addition, the severity of chronic progressive nephropathy was increased slightly in the male rats in the 1.0% group. There were no compound-related findings present in the tissues examined from the male or female rats in the 0.25% group.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 250 other: mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical signs
- food consumption and compound intake
- gross pathology
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The No observed adverse effect level (NOAEL) for the substance 2-methyl-1H-isoindole-1,3(2H)-dione is determined to be 250 mg/kg bw/day.
- Executive summary:
Groups of 10 rats /sex were fed 2-methyl-1H-isoindole-1,3(2H)-dione at levels of 0, 0.25, 0.5 and 1.0%. All rats were observed for mortality twice each day. Clinical signs and body weights were recorded at initiation and weekly thereafter. Food consumption was recorded weekly. After 30 days of treatment, all surviving rats were fasted overnight and weighed prior to terminal sacrifice and necropsy. At necropsy the liver and kidneys were weighed. The following tissues were saved from all animals: brain, pituitary, thoracic spinal cord, eyes, salivary glands (mandibular), stomach, trachea, thymus esophagus, heart, spleen, adrenals, pancreas, duodenum, jejunum, ileum, colon, cecum, mesenteric lymph node, urinary bladder, testes with epididymides and prostate (males), ovaries and uterus (females), femur, bone marrow (costochondral junction), lungs, liver, kidneys, thyroid (with parathyroids), skeletal muscle, and all gross lesions. Microscopic evaluation was conducted on sections of the lungs, liver, brain and kidneys from rats of all treatment groups. A necropsy also was performed on all rats that were sacrificed in extremis or were found dead during the study. One male rat in the 0.25% group died on Day 26 of the study. Statistically significant decreases in body weight of both male and female rats in the 0.5 and 1.0% groups (6% and 18% lower than controls for males and 4% and 11% lower than control for females, respectively) were noted during the fourth week of exposure. Mean food consumption values of the treated male and female rats were lower than control at some measurement periods, but the food consumption value for the male rats in the 1.0% group during the final week of exposure was the only statistically significant decrease noted. Mean compound consumption for the male rats in the 0.25, 0.50 and 1.0% groups ranged from 146 to 203 mg/kg/day, 330 to 403 mg/kg/day and 685 to 815 mg/kg/day, respectively. The mean compound consumption for the female rats in the 0.25, 0.5 and 1.0% groups range from 197 to 226 mg/kg/day, 409 to 573 mg/kg/day and 921 to 1100 mg/kg/day, respectively. The gross pathology revealed no treatment-related effects in any PI-treated group. Mean liver relative to terminal body weight was increased for both sexes and mean kidney weight relative to terminal body weight was increased for males at 1.0%. Microscopic evaluation revealed compound-related findings of centrilobular to diffuse hepatocellular enlargement in rats of both sexes in the 0.5 and 1.0% treatment groups. In addition, the severity of chronic progressive nephropathy was increased slightly in the male rats in the 1.0% group. There were no compound-related findings present in the tissues examined from the male or female rats in the 0.25% group.
Thus, the No observed adverse effect level (NOAEL) for the substance2-methyl-1H-isoindole-1,3(2H)-dione is determined to be 250 mg/kg bw/day.
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