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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
Endpoint summary
Administrative data
Description of key information
Repeated dose toxicity: via oral route;
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.
Repeated dose toxicity; via Inhalation route
According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 2-amino-4-nitrophenol, which is reported as 0.000034952875 mmHg at 25°C as well as the particle size distribution indicates that the majority particle size is above 75 micro meter. Thus, exposure by inhalation is also unlikely for 2-amino-4-nitrophenol given the comparatively larger size of the particulates.
Repeated dose toxicity; via Dermal route
NOAEL was considered to be 1000 mg/kg/day for test chemical in New Zealand White male and female rabbit for 13 weeks by dermal route.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- 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
- 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
- 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 - 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
- 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.
- 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. - 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. - 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
- Critical effects observed:
- not specified
- 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.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 250 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- K2 data from qualified publication
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: dermal
- 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
- Qualifier:
- according to guideline
- Guideline:
- other: As mention below
- Principles of method if other than guideline:
- Thirteen week study was conducted to evaluate the toxic effects of repeated administration of test chemical.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Not specified
- Type of coverage:
- open
- Vehicle:
- other: 6% Hydrogen peroxide
- Details on exposure:
- TEST SITE
The sites of application on the dorsolateral aspects of the thoracic-lumbar area (one on each side of the midline) were alternated to minimize skin irritation.
REMOVAL OF TEST SUBSTANCE
The rabbits were restrained in holding stocks for 1 hr following each application and were then shampooed, rinsed, dried, and returned to their cages
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test materials, prepared by mixing equal volumes of the dye solution and 6% hydrogen peroxide, were applied topically at a dose of 1000 mg/kg (
1 ml/kg) application.
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- Twice weekly
- Remarks:
- 1000 mg/kg (1 ml/kg)
- No. of animals per sex per dose:
- Control – I: 6male and 6 females
Control - II : 6male and 6 females
Control - III: 6male and 6 females
2-Amino-4-nitrophenol : 6male and 6 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- The hair at the site of application on the back and sides of each rabbit was clipped short throughou
t the study. The application sites on three animals of each sex in each group were abraded on the f
irst treatment day of each week. The rabbits were restrained in holding stocks for 1 hr following each
application and were then shampooed, rinsed, dried, and returned to their cages. - Observations and examinations performed and frequency:
- Observations and examinations performed and frequency
BODY WEIGHT: Yes,
The animals were weighed weekly during the study.
HAEMATOLOGY: Yes
Hematologic determinations was performed on all animals at 0, 3, 7, and 13 wk.
Following parameters was examined :
Blood count, Methemoglobin, Fasting blood sugar
CLINICAL CHEMISTRY: Yes
Clinical chemistry determinations was performed on all animals at 0, 3, 7, and 13 wk.
Following parameters was examined :
Blood urea nitrogen, Alkaline phosphatase, Serum glutamic oxaloacetic transaminase
URINALYSIS: Yes
Examination of urine was performed on all animals at 0, 3, 7, and 13 wk.
Urine was examined for color, pH, albumin, glucose, occult blood, and microscopic elements.
OTHER: Organ weights was determined. - Sacrifice and pathology:
- All survivors were sacrificed after 13 wk and examined for gross abnormalities. Organ-body weight ra
tios were determined for liver,kidneys, adrenals, heart, thyroid, spleen, and brain.
Twenty-five tissues were examined microscopically.
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- Statistical analysis of the data on body weight gains, hematology, clinical chemistry, and absolute and relative organ weights was performed using the analysis of variance F test and Student's t test.When variances differed significantly, Student's t test was modified (t')and Cochran's approximation was utilized.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No significant clinical sign was obsrved at dose level of 1000 mg/kg of treated group compare to control.
- Dermal irritation:
- not specified
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Five control and five test animals died during the study due to complications resulting from cardiac puncture while collecting blood.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No significant clinical sign was obsrved at dose level of 1000 mg/kg of treated group compare to control.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No effects (There were scattered statistically significant differences in the hematologic values between test and control groups at the various sampling intervals. However, these differences were
not considered to be of toxicologic significance because of either the direction or continuity of the differences or the fact that they fell within the range of historical control values.) - Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- There were a few instances when there were statistically significant differences in relative organ weights between a test group and the combined controls but the differences were not significant when they were compared with each control group separately.
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No microscopic lesions were seen that were judged to be due to the administration of the hair dye formulations.
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- 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
- Critical effects observed:
- not specified
- Conclusions:
- NOAEL was considered to be 1000 mg/kg/day for test chemical in New Zealand White male and female rabbit for 13 weeks by dermal route.
- Executive summary:
Thirteen week study was conducted to evaluate the toxic effects of test substance. Test substance was applied dermally twice weekly for 13 week to groups of 12 adult New Zealand white male and female rabbits at a dose concentration of 1000 mg/kg. The animals were observed for dermal irritation,clinical sign, mortality, body weight, organ weight, gross and histopathology.There was no evidence of induced systemic effects. No effects on body weight. Microscopic examination of 25 tissues from each animal gave no indication of histomorphologic evidence of toxicity. No gross abnormalities were seen at necropsy. No dye discoloration of urine was seen at any time during the test or at necropsy.
Therefore NOAEL of the study was considered to be 1000 mg/kg for test chemical in New Zealand White male and female rabbit for 13 weeks by dermal route.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rabbit
- Quality of whole database:
- K2 data from qualified publication
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
The data available for the test chemical was reviewed to determine the toxic nature of 2-amino-4-nitrophenol (99-57-0) repeated exposure by oral route. The study is as mentioned below:
Repeated dose toxicity: via oral route;
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.
Repeated dose toxicity study was assessed for test substance to evaluate its possible toxic effect .The test chemical was exposed to the B6C3F1 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. Mortality and significant clinical sign were observed at the 500 and 1000 mg/kg/day. 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 B6C3F1 male and female rats for 13 weeks by oral gavage.
Repeated dose toxicity; via Inhalation route
According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance2-amino-4-nitrophenol (99-57-0) , which is reported as 0.000034952875 mmHg at 25°C as well as the particle size distribution indicates that the majority particle size is above 75 micro meter. Thus, exposure by inhalation is also unlikely for 2-amino-4-nitrophenol given the comparatively larger size of the particulates.
Repeated dose toxicity; via Dermal route
Thirteen week study was conducted to evaluate the toxic effects of test substance. Test substance was applied dermally twice weekly for 13 week to groups of 12 adult New Zealand white male and female rabbits at a dose concentration of 1000 mg/kg. The animals were observed for dermal irritation,clinical sign, mortality, body weight, organ weight, gross and histopathology.There was no evidence of induced systemic effects. No effects on body weight. Microscopic examination of 25 tissues from each animal gave no indication of histomorphologic evidence of toxicity. No gross abnormalities were seen at necropsy. No dye discoloration of urine was seen at any time during the test or at necropsy.
Therefore NOAEL of the study was considered to be 1000 mg/kg for test chemical in New Zealand White male and female rabbit for 13 weeks by dermal route.
Based on the data available for the test chemical 2-amino-4-nitrophenol (99-57-0) not likely to exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.
Justification for classification or non-classification
Based on the data available for the test chemical 2-amino-4-nitrophenol (99-57-0) not likely to exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.
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