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EC number: 204-508-5 | CAS number: 121-92-6
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- 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 is from J check
Data source
Reference
- Reference Type:
- other:
- Title:
- Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test of test chemical by oral administration in rats
- Author:
- National institute of technology and evaluation
- Year:
- 2 015
- Bibliographic source:
- Japan Chemicals Collborative Knowledge Database (J-check), 2015
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Principles of method if other than guideline:
- Combined repeated dose reproduction / developmental toxicity Screen of test chemical was performed in rats orally
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- Data is from J check
Test material
- Reference substance name:
- 3-nitrobenzoic acid
- EC Number:
- 204-508-5
- EC Name:
- 3-nitrobenzoic acid
- Cas Number:
- 121-92-6
- Molecular formula:
- C7H5NO4
- IUPAC Name:
- 3-nitrobenzoic acid
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): m-nitrobenzoic acid
- Molecular formula (if other than submission substance): C7H5NO4
- Molecular weight (if other than submission substance): 167.121
- Substance type: Organic
- Physical state: solid
- Purity : 99.2%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data available
- Age at study initiation: 9 weeks old (initiation of dosing)
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: 0.1w/v% Tween 80 + 0.5w/v% Sodium carboxymethylcellulose solution
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Test chemical was dissolved in 0.1 w/v% Tween 80 + 0.5 w/v% Sodium carboxymethylcellulose solution at dose levels of 0, 20, 100 or 500 mg/Kg bw/day
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): 0.1 w/v% Tween 80 + 0.5 w/v% Sodium carboxymethylcellulose solution
- Concentration in vehicle: 0, 20, 100 or 500 mg/kg bw/day
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 42 days
- Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 20, 100 or 500 mg/kg/day
Basis:
no data
- No. of animals per sex per dose:
- Total: 116
0 mg/kg/day: 12 male, 12 female
20 mg/kg/day: 12 male, 12 female
100 mg/kg/day: 12 male, 12 female
500 mg/kg/day: 12 male, 12 female
Recovery:
0 mg/kg/day: 5 male, 5 female
500 mg/kg/day: 5 male, 5 female
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. Mortality were observed
DETAILED CLINICAL OBSERVATIONS: Yes, animal were observed for salivation
- Time schedule: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: Observed during dosing period
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 : 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:
No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. Red blood cell count, hemoglobin concentration and hematocrit value were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. A/G ratio, Pi, K, BUN, TP, Cl and ALT were examined.
OTHER:
Organ weight: Brain R, Liver R, Kidney R, Testes A/R, Epididymides A/R, Thymus A and Spleen A/R were weighed. - Oestrous cyclicity (parental animals):
- Any irregularities in the estrous cycle were investigated.
- Sperm parameters (parental animals):
- No data
- Litter observations:
- Number of live offspring, clinical signs and body weight were observed.
- Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: No detailed data available
- Maternal animals: No data available
GROSS NECROPSY and HISTOPATHOLOGY / ORGAN WEIGHTS
The target organs for the study were Stomach, Bone, Testes, Epididymides, (Female genital tract) - Postmortem examinations (offspring):
- No detailed data available
- Statistics:
- No data
- Reproductive indices:
- Gestation index, delivery index, number of corpora lutea, number of implantations, implantation index and number of offspring delivered were observed
- Offspring viability indices:
- Offspring viability on day 0 and 4 were observed
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Salivation was observed in 500 mg/kg bw/day treated male and female rats as compared to control and and decrease in locomotor activity, irregular respiration, prone position and drastic worsening was observed in female rat.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- When treated with 500 mg/kg bw/day, three female rats died as compared to control.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Restrained body weight gain was observed in 500 mg/kg bw/day treated male rat as compared to control.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- On day 8, Decrease in the food consumption was observed in 500 mg/kg bw/day treated male and female rat as compared to control.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No effects was observed in treated male and female rat as compared to control.
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- In male rat, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, Decrease sperm in the epididymides duct, Cell debris in epididymides duct and Increase in the trabecular bone in femur bone were observed in 500 mg/kg bw/day during treatment and recovery.
In female rat, Squamous hyperplasia and Erosion in forestomach during test and Increase in trabecular bone in femur bone during test and Recovery at in 500 mg/kg bw/day treated female rats. - Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- No effects were observed on estrous cycle, irregular estrous cycle, mating index, mating days until copulation, number of estrous stages without mating.
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- No effects were observed on estrous cycle, irregular estrous cycle, mating index, mating days until copulation, number of estrous stages without mating, fertility index, gestation period and parturition or maternal behavior of treated rat.
Reproductive performance:
Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered were observed in 500 mg/kg bw/day treated female rats.
Details on results (P0)
When treated with 500 mg/kg bw/day, three female rats died as compared to control.
Clinical signs:
Salivation was observed in 500 mg/kg bw/day treated male and female rats as compared to control and and decrease in locomotor activity, irregular respiration, prone position and drastic worsening was observed in female rat.
Body weight and weight gain:
Restrained body weight gain was observed in 500 mg/kg bw/day treated male rat as compared to control.
Food consumption:
On day 8, Decrease in the food consumption was observed in 500 mg/kg bw/day treated male and female rat as compared to control.
Urinalysis:
No effects was observed in treated male and female rat as compared to control.
Hematology:
Decrease in the RBC, Hgb and Hct level were observed in 500 mg/kg bw/day treated male and female rat as compared to control.
Blood chemistry:
In male rats, Increase in the A/G ratio, Pi, K, and Decrease in Blood Urea Nitrogen, total protein and Cl level were observed in 500 mg/kg bw/day.
In female rats, Increase in ALT was observed in 500 mg/kg bw/day.
Organ weight:
In male rats, Increase in Relative brain, liver and kidney weight and Decrease in Absolute and Relative testes and epididymides weight during test and recovery and Absolute thymus weight during test were observed in 500 mg/kg bw/day.
In female, Increase in Relative liver and spleen weight during test and recovery and Absolute spleen and kidney weight in recovery and Decrease in Absolute thymus weight during test were observed in 500 mg/kg bw/day.
Histopathology:
In male rat, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, Decrease sperm in the epididymides duct, Cell debris in epididymides duct and Increase in the trabecular bone in femur bone were observed in 500 mg/kg bw/day during treatment and recovery.
In female rat, Squamous hyperplasia and Erosion in forestomach during test and Increase in trabecular bone in femur bone during test and Recovery at in 500 mg/kg bw/day treated female rats.
Reproductive function:
No effects were observed on estrous cycle, irregular estrous cycle, mating index, mating days until copulation, number of estrous stages without mating, fertility index, gestation period and parturition or maternal behavior of treated rat.
Reproductive performance:
Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered were observed in 500 mg/kg bw/day treated female rats.
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive function (oestrous cycle)
- reproductive performance
- other: Effects were observed at 500 mg/kg bw/day
- Remarks on result:
- other: effects observed at 500mg/kg bw
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No effect were observed on Clinical signs of pups
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- When treated with 500 mg/kg/day, decrease in number of live pups on day 4 were observed as compared to control.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No change in body weight of pups was observed in treated rats.
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No abnormal changes were observed in Gross pathology of pups.
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Details on results (F1)
Clinical signs: No effect were observed on Clinical signs of pups
Body weight: No change in body weight of pups was observed in treated rats.
Food consumption: No data available
Gross pathology: No abnormal changes were observed in Gross pathology of pups.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- mortality
- body weight and weight gain
- gross pathology
- other: No of pups delivered. The effects were observed at 500 mg/Kg bw/day
- Remarks on result:
- other: No of pups delivered. The effects were observed at 500 mg/Kg bw/day
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The no-observed-adverse-effect-level (NOAEL) was considered to be 100 mg/kg/day for F0 and F1 generation when Crl:CD(SD) male and female rat were treated with test chemical orally.
- Executive summary:
In Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test, Crl:CD (SD) male and female rats were treated with test chemical in the concentration of 0, 20, 100 and 500 mg/kg bw/day orally by gavage. In F0 generation, when treated with 500 mg/kg/day, three female rats died, Salivation in male and female rat was noted, restrained body weight gain in male rat and decrease in the food consumption on day 8 in male and female rat were observed. Similarly, Decrease in the RBC, Hgb and Hct level in male and female rat, Increase in A/G ratio, Pi, K and Decrease in Blood Urea Nitrogen, total protein, Cl level in male rat and Increase in ALT level in female rat were observed in 500 mg/kg/day. In addition, Increase in Relative brain, liver and kidney weight and Decrease in absolute and relative testes and epididymides weight during test and recovery and absolute thymus weight during test in male rat and Increase in relative liver and spleen weight during test and recovery and absolute spleen and kidney weight in recovery and Decrease in absolute thymus weight during test in female, Squamous hyperplasia, Erosion and Focal inflammatory cell infiltration in the forestomach, Small and soft testes, Small epididymides, Degeneration in seminiferous tubular epithelium of testes, decrease sperm and cell debris in epididymides duct and an increase in the trabecular bone in femur bone in male rat and squamous hyperplasia and erosion in forestomach during test and an increase in trabecular bone in femur bone during test and recovery in female rat treated with 500 mg/kg/day. Decrease in gestation index, delivery index, number of corpora lutea, number of implantation sites, implantation index and number of pups delivered in F0 female and a decrease in number of pups delivered, number of live pups on day 0 and number of live pups on day 4 were observed in F1 generation treated with 500 mg/kg bw/day female rats. Based on the observations made, the reproductive No Observed Adverse Effect Level (NOAEL) was considered to be 100 mg/kg body/day for F0 and F1 generation when Crl:CD (SD) male and female rats were treated with test chemical.
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