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EC number: 202-767-9 | CAS number: 99-57-0
- 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

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- data from handbook or collection of data
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- TOXICOLOGY AND CARCINOGENESIS STUDIES OF test substance
- Author:
- National Toxicology Program Technical Report Series.
- Year:
- 1 988
- Bibliographic source:
- NTP
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: As mention below
- Principles of method if other than guideline:
- Repeated dose toxicity study was evaluated for test chemical in Fischer 344 male and female rats for 13 weeks by oral gavage.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2-amino-4-nitrophenol
- EC Number:
- 202-767-9
- EC Name:
- 2-amino-4-nitrophenol
- Cas Number:
- 99-57-0
- Molecular formula:
- C6H6N2O3
- IUPAC Name:
- 2-amino-4-nitrophenol
- Details on test material:
- - Name of test material (as cited in study report): 2-amino-4-nitrophenol
- Molecular Formula: C6H6N2O3
- Molecular Weight: 154.125 g/mol
- SMILES Notation: C1=CC(=C(C=C1[N+](=O)[O-])N)O
- InChI: 1S/C6H6N2O3/c7-5-3-4(8(10)11)1-2-6(5)9/h1-3,9H,7H2
- Substance type: Organic
- Physical state: solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:Charles River Breeding Laboratories
- Age at study initiation:7 wk
- Diet (e.g. ad libitum):NIH 07 RatRation, ad libitum
- Water (e.g. ad libitum):Automatic watering system, ad libitum
- Housing:Animals were caged in polycarbonated cages with Aspen wood chips in a controlled
environment.
ENVIRONMENTAL CONDITIONS
- Temperature (°C):21.1-24.4°C
- Humidity (%): 40%-60%
- Photoperiod (hrs dark / hrs light):12 hrs dark/light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- Justification for use and choice of vehicle (if other than water): Corn oil
- Concentration in vehicle: 0, 62.5, 125, 250, 500 or 1000 mg/kg/day
- Amount of vehicle (if gavage): 5 ml/kg/day
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyses for test substance in dose mixtures by methanolic extraction and spectrophotometric quantitation were performed by the study and analytical chemistry laboratories to determine if the suspensions were formulated properly. Good agreement was generally found between the study and analytical chemistry laboratories.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 5 days per week
Doses / concentrations
- Remarks:
- 0, 62.5, 125, 250, 500, or 1,000 mg/kg
- No. of animals per sex per dose:
- Total 120 animals
0 mg/kg/day 10 male and 10 female
62.5 mg/kg/day 10 male and 10 female
125 mg/kg/day 10 male and 10 female
250 mg/kg/day 10 male and 10 female
500 mg/kg/day 10 male and 10 female
1000 mg/kg/day 10 male and 10 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Animals were distributed to weight classes and assigned to groups according to two tables of random numbers with 5 animals per cage. Animals were identified by toe clip.
Examinations
- Observations and examinations performed and frequency:
- Observations and examinations performed and frequency
CAGE SIDE OBSERVATIONS: Yes,Rats were observed twice per day.
DETAILED CLINICAL OBSERVATIONS: Yes ,Clinical signs were recorded.
BODY WEIGHT: Yes,Body weights were recorded once per week for the first 12 weeks of the studies
and once per month thereafter. Mean body weights were calculated for each group. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Necropsy performed on all animals. Histologic exam performed on animals dying before the end of
the studies, on animals with gross lesions, and all vehicle control and high dose animals. Kidney was
examined in all mice and the liver was weighed at necropsy.
HISTOPATHOLOGY: Yes
Histopathologic examinations were performed on all grossly visible lesions in all dose groups. - Statistics:
- Data recording:Data were recorded in the Carcinogenesis Bioassay Data System, including des criptive information on the chemicals, animals, experimental design, survival, body weight and indi vidual pathology results.
Survival analyses
The probability of survival was estimated by a product-limit procedure and is presented in the form of graphs. Animals were censored from the survival analyses at the time they were found to be missing or dead from other than natural causes.
Calculation of incidence
The incidence of neoplastic or nonneoplastic lesions is given as the ratio of the number of animals bearing such lesions at a specific anatomic site to the number of animals in which that site was examined. In most instances, the denominators include only those animals for which the site was examined histologically.
Analysis of Tumor Incidence
Three statistical methods are used to analyzetumor incidence data: life table tests, incidental tumor an alysis and Fisher exact/Cochran-Armitage trend analyses.
Historical Control Data
Although the concurrent control group is always the first and most appropriate control group used for evaluation, there are certain instances in which historical control data can be helpful in the overall assessment of tumor incidence.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant clinical signs such as Diarrhea and lethargy were observed for rats that received 500 and 1,000 mg/kg/day in treated group compare to control
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Mortality observed in 2/10 male rats at 1000 mg/kg/day treated dose compare to control.
Mortality observed in 2/10 female rats at 500 mg/kg/day treated dose compare to control. - Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No significant change were observed in final mean body weights at dose level of 62.5, 125, 250, 500, or 1,000 mg/kg of treated group compare to control.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Liver weight to body weight ratios of rats that received 500 mg/kg were significantly greater than those of vehicle controls.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Liver
Microscopic examination of the liver did not reveal any histopathologic changes attributable to chemical exposure.
Kidney
Mild to severe mineralization of the renal cortex and mild to severe degeneration of the renal tubular epithelium were observed in male rats that received 500 or 1000 mg/kg/day and in females that received 1000 mg/kg/day.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 250 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant effect were observed at this dose
- Remarks on result:
- other: No toxic effects were observed
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 250 mg/kg/day for test chemical in Fischer 344 male and female rats for 13 weeks by oral gavage.
- Executive summary:
Repeated dose toxicity study was assessed for test substance to evaluate its possible toxic effect .The test chemical was exposed to the Fischer 344 male and female rats for 13 weeks by oral gavage. The test substance was exposed at the concentration of 0, 62.5, 125, 250, 500, or 1,000 mg/kg by using corn oil as vehicle. The above mention doses were decided based on dose finding study. The animals were observed for clinical sign, mortality, body weight, organ weight, gross and histopathology. Significant clinical signs such as Diarrhea and lethargy were observed for rats that received 500 and 1,000 mg/kg/day in treated group compare to control. Mortality were also observed in 2/10 male rats at 1000 mg/kg/day treated dose compare to control .Mortality observed in 2/10 female rats at 500 mg/kg/day treated dose compare to control. No significant change were observed in final mean body weights at dose level of 62.5, 125, 250, 500, or 1,000 mg/kg of treated group compare to control. No mortality or clinical signs were observed at the 250 mg/kg/day treated dose in male and female rats compare to control. Therefore NOAEL was considered to be 250 mg/kg/day for test chemical in Fischer 344 male and female rats for 13 weeks by oral gavage.
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