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EC number: 207-803-7 | CAS number: 495-54-5
- 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
Acute
toxicity: oral
Under
the condition of the study, the acute oral LD50 (Cut-off value) of
4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) was 1000 mg/kg body
weight. Thus, it was concluded that the acute toxicity study of
4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), when administered
via oral route in Sprague Dawley rats falls into the “Category 4 (300 –
≤ 2000)” criteria of CLP.
Acute
toxicity: inhalation
The
study need not be conducted because exposure of humans via inhalation is
not likely taking into account the vapour pressure of the substance
and/or the possibility of exposure to aerosols, particles or droplets of
an inhalable size.
Acute
toxicity: dermal
It
was concluded that the acute dermal median lethal dose (LD50) of
4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), when administered
to male and female Sprague Dawley rats was found to be greater than 2000
mg/kg body weight. Thus, according to CLP criteria for acute toxicity
rating for the chemicals, it infers that
4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) does not classify as
an acute dermal toxicant. CLP Classification: “Unclassified”.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from experimental study report.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Principles of method if other than guideline:
- The purpose of this study was to assess the Toxicological profile of test item to a single administration via oral route to Sprague Dawley rats. This study was designed to determine the acute toxicity at fixed dose levels by oral route of the test item.
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- no
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Test Item: 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5)
- Source of test material: Sustainability Support Services (Europe) AB, Sweden
- Batch No. of test material: KCP/FS/43/17
- Manufacturing Date: January; 2017
- Expiration date of the lot/batch: December; 2017
- Purity test date: No data
- Consistency: Solid, powder
RADIOLABELLING INFORMATION (not applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Test Item and prepared formulation(s) were stored at ambient temperature.
- Stability under test conditions: No data available
- Solubility and stability of the test substance in the solvent/vehicle: No data available
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data available
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was suspended in Polyethylene Glycol - 400. The formulation was prepared fresh on the day of dosing.
- Preliminary purification step (if any): No data available
- Final dilution of a dissolved solid, stock liquid or gel: No data available
- Final preparation of a solid: No data available
FORM AS APPLIED IN THE TEST (if different from that of starting material): No data available
OTHER SPECIFICS:
Safety Precautions: Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses). - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Female rats of the age of approximately 8 to 12 weeks old were used at the commencement of its dosing.
- Weight at study initiation: Body weight range was 197.2 to 208.2 grams.
Body weights at the start :
Female
Mean : 201.32 g (= 100 %)
Minimum : 197.2 g (- 2.05 %)
Maximum : 208.2 g (+ 3.42 %)
Total No. of animals : 9
- Identification: Each female rat was individually identified by the picric acid marking.
- Fasting period before study: Approximately 16 hours or more.
- Housing: The rats were housed in polycarbonate cages.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 22.3 degree centigrade.
- Humidity (%): 55.1% to 58.4%
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
IN-LIFE DATES: 12-06-2017 to 30-06-2017 - Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Remarks:
- Polyethylene Glycol - 400
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg and 2000 mg/kg
- Amount of vehicle (if gavage): No data
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.
DOSAGE PREPARATION (if unusual): No data available
CLASS METHOD (if applicable) No data
- Rationale for the selection of the starting dose: No data - Doses:
- Dose Group I : 300 mg/kg
Dose Group I : 300 mg/kg
Dose Group II : 2000 mg/kg - No. of animals per sex per dose:
- Three females were used at each step.
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality and morbidity, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at immediately (0 to 5 minutes), 5, 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
Body weights:
Individual animal body weights were recorded, before fasting, prior to administration of the test item (fasting body weights), weekly thereafter and at termination on day 14. Weight changes were calculated and recorded.
Gross Pathology:
Necropsy was performed on all animals, found dead and sacrificed at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).
Histopathology:
Gross pathological examination revealed distended stomach with test item coloured ingesta and small and large intestine with liquid test item coloured ingesta the localized colouration imparted to the abdominal organs is of the test item and no gross abnormality observed except colouration hence, no organ collected for histopathology. - Statistics:
- No data
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 1 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: LD50 cut off value
- Mortality:
- Group I
Step I :
Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days and were free of signs of toxicity at 6 hours after the dosing.
Group I
Step II :
Animals treated at the dose level of 300 mg/kg body weight: All animals survived through the study period of 14 days.
Group II
Step I :
Animals treated at the dose level of 2000 mg/kg body weight: Two animals died on day 1 after the dosing. - Clinical signs:
- Group I
Step I :
Animals treated at the dose level of 300 mg/kg body weight resulted in reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing. All animals survived through the study period of 14 days and were free of signs of toxicity at 6 hours after the dosing.
Group I
Step II :
Animals treated at the dose level of 300 mg/kg body weight resulted in reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing. All animals survived through the study period of 14 days and were free of signs of toxicity at 6 hours after the dosing.
Group II
Step I :
Animals treated at the dose level of 2000 mg/kg body weight resulted in polyurea, diarrhoea, reduced locomotor activity and ataxic gait with onset at 30 minutes to day 1 after the dosing. The only surviving animal was free of signs of toxicity on day 7 after the dosing. - Body weight:
- Group I
Step I (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 1.97% and 9.21% respectively.
Group I
Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 2.02% and 9.58% respectively.
Group II
Step I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 1.93% and 10.09% respectively. - Gross pathology:
- Gross pathological examination did not reveal any abnormalities in animals sacrificed terminally from 300 mg/kg and 2000 mg/kg dose groups.
Gross pathological examination revealed distended stomach with test item coloured ingesta and small and large intestine with liquid test item coloured ingesta in found dead animals from 2000 mg/kg dose group. - Other findings:
- No data available
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- Under the condition of the study, the acute oral LD50 (Cut-off value) of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) was 1000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), when administered via oral route in Sprague Dawley rats falls into the “Category 4 (300 – ≤ 2000)” criteria of CLP.
- Executive summary:
The study now reported was designed and conducted to determine the acute oral toxicity profile of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg resulted in reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing and no mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg resulted in reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing and no mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in polyurea, diarrhoea, reduced locomotor activity and ataxic gait with onset at 30 minutes to day 1 after the dosing. Two animals died on day 1 after the dosing.
All animals from 300 mg/kg dose group survived and exhibited normal body weight gain through the study period of 14 days.
Gross pathological examination did not reveal any abnormalities in animals sacrificed terminally from 300 mg/kg and 2000 mg/kg dose groups.
Gross pathological examination revealed distended stomach with test item coloured ingesta and small and large intestine with liquid test item coloured ingesta in found dead animals from 2000 mg/kg dose group.
The acute oral LD50 (Cut-off value) of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) was 1000 mg/kg body weight.
Thus, it was concluded that the acute toxicity study of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), when administered via oral route in Sprague Dawley rats falls into the “Category 4 (300 – ≤ 2000)” criteria of CLP.
Reference
Table No. I
Summary of Clinical Signs of Toxicity and Mortality
Test System : Sprague Dawley Rat
Sex : Female
Group I :
Step No. |
Dose mg/kg |
Observed Signs |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
I |
300 |
Reduced locomotor activity |
1 |
2 |
4 hrs. |
0/3 |
Ataxic gait |
1 |
2 |
4 hrs. |
Group I :
Step No. |
Dose mg/kg |
Observed Signs |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
II |
300 |
Reduced locomotor activity |
1 |
4 |
4 hrs. |
0/3 |
Ataxic gait |
1 |
4 |
4 hrs. |
Group II :
Step No. |
Dose mg/kg |
Observed Signs |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
I |
2000 |
Polyurea |
1 |
9 |
Day 1 - Day 6 |
2/3 |
Diarrhoea |
3 |
7,8,9 |
4 hrs. - 6 hrs. |
|||
Reduced locomotor activity |
3 |
7,8 9 |
30 min. - 6 hrs. 30 min. - 4 hrs. |
|||
Ataxic gait |
3 |
7,8 9 |
1 hr. - 6 hrs. 1 hr. - Day 6 |
Table No.II
Mean Body Weight and Percent Body Weight Gain (g)
Test System : Sprague Dawley Rat
Sex : Female
Group I :
Step No. |
Dose (mg/kg body weight) |
|
Before Fasting Body weight |
Body weight Day 7 |
% body weight gain day 0-7 |
Body weight Day 14 |
% body weight gain day 7- 14 |
% body weight gain day 0- 14 |
I |
300 |
Mean |
205.13 |
209.17 |
1.97 |
224.00 |
7.10 |
9.21 |
± SD |
2.91 |
3.23 |
0.61 |
1.28 |
1.28 |
1.42 |
Group I :
Step No. |
Dose (mg/kg body weight) |
|
Before Fasting Body weight |
Body weight Day 7 |
% body weight gain day 0-7 |
Body weight Day 14 |
% body weight gain day 7- 14 |
% body weight gain day 0- 14 |
II |
300 |
Mean |
200.37 |
204.40 |
2.02 |
219.57 |
7.42 |
9.58 |
± SD |
2.06 |
2.35 |
1.14 |
3.25 |
1.45 |
0.50 |
Group II :
Step No. |
Dose (mg/kg body weight) |
|
Before Fasting Body weight |
Body weight Day 7 |
% body weight gain day 0-7 |
Body weight Day 14 |
% body weight gain day 7- 14 |
% body weight gain day 0- 14 |
I |
2000 |
Mean |
198.47 |
201.00 |
1.93 |
217.10 |
8.01 |
10.09 |
± SD |
2.11 |
- |
- |
- |
- |
- |
Table No.III
Summary of Gross Pathological Findings
Test System : Sprague Dawley Rat
Sex : Female
Group I :
Step No. |
Dose mg/kg |
Animal Numbers |
Animal Fate |
Gross Pathological Findings |
I |
300 |
1 - 3 |
TS |
No abnormality detected |
Group I :
Step No. |
Dose mg/kg |
Animal Numbers |
Animal Fate |
Gross Pathological Findings |
II |
300 |
4 - 6 |
TS |
No abnormality detected |
Group II :
Step No. |
Dose mg/kg |
Animal Numbers |
Animal Fate |
Gross Pathological Findings |
I |
2000 |
7, 8 |
FD |
Stomach : Distended with test item coloured ingesta. Small and large intestine with liquid test item coloured ingesta. |
9 |
TS |
No abnormality detected |
FD = Found dead
TS = Terminal Sacrifice
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 300 mg/kg bw
- Quality of whole database:
- Data is of K1 reliability and is obtained from experimental study report.
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from experimental study report.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Principles of method if other than guideline:
- This study was designed to determine the dermal LD50 of the test item (up to 2000 mg/kg) or to establish a non-lethal dose level of 2000 milligram of test item per kilogram of body weight.
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Test Item: 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5)
- Source of test material: Sustainability Support Services (Europe) AB
- Batch No.of test material: KCP/FS/43/17
- Manufacturing Date: January; 2017
- Expiration date of the lot/batch: December; 2017
- Purity test date: No data available
- Consistency: Solid, powder
RADIOLABELLING INFORMATION (Not applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient Temperature
- Stability under test conditions: No data available
- Solubility and stability of the test substance in the solvent/vehicle: No data available
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data available
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was grounded to fine powder prior to application. The particulates were moistened
with distilled water before application.
- Preliminary purification step (if any):No data available
- Final dilution of a dissolved solid, stock liquid or gel: No data available
- Final preparation of a solid: No data available
FORM AS APPLIED IN THE TEST: Paste
OTHER SPECIFICS:
Safety Precautions : Safety precautions included use of protective clothing, gloves, masks and eye protection (glasses). - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females nulliparous and non-pregnant: No data available
- Age at study initiation: Young adult male and female rats aged between 8 – 12 weeks were used.
- Weight at study initiation: The weight range of approximately 213.4 to 252.2 grams at initiation of dosing.
Body weights at the start :
Male
Mean : 245.26 g (= 100 %)
Minimum : 239.8 g (- 2.23 %)
Maximum : 252.2 g (+ 2.83 %)
Total No. of animals : 5
Female
Mean : 218.46 g (= 100 %)
Minimum : 213.4 g (- 2.32 %)
Maximum : 222.7 g (+ 1.94 %)
Total No. of animals : 5
- Identification: Each rat was individually identified by the cage number.
- Fasting period before study: No data available
- Housing: The rats were individually housed in polycarbonate cages with paddy husk as bedding.
- Diet (e.g. ad libitum): Rodent feed supplied by the Nutrivet Life Sciences, Pune, was provided ad libitum from individual feeders.
- Water (e.g. ad libitum): Water was provided ad libitum from individual bottles attached to the cages. All water was from a local source and passed through the reverse osmosis membrane before use.
- Acclimation period: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6 to 21.6 degree centigrade.
- Humidity (%): 55.0% to 58.4%.
- Air changes (per hr): Ten to fifteen air changes per hour.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.
IN-LIFE DATES: 12-06-2017 to 27-06-2017 - Type of coverage:
- semiocclusive
- Vehicle:
- water
- Remarks:
- (Distilled water)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: Trunk (dorsal surface and sides from scapular to pelvic area)
- % coverage: Approximately 10% of the body surface area.
- Type of wrap if used: Porous gauze dressing and non-irritating tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water was used to remove residual test item.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: No data available
- For solids, paste formed: Yes
VEHICLE
- Amount(s) applied (volume or weight with unit): No data available
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Duration of exposure:
- 24 hours
- Doses:
- A single dose of 2000 mg of the test item per kilogram of body weight was administered to ten rats (five males and five females).
- No. of animals per sex per dose:
- 10 (5/sex).
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily
- Necropsy of survivors performed: Yes
- Other examinations performed:
Clinical Observations and General Appearance:
Animals were observed for clinical signs, mortality, until sacrifice.
Onset, duration and severity of any sign were recorded. The clinical signs and mortality observations were conducted at 10, 30, 60 minutes, 2, 4 and 6 hours on the day of dosing and once daily thereafter for 14 day. Daily observation was done as far as possible at the same time.
The observations were included general clinical signs, observations of eyes, mucous membranes, respiratory, circulatory system and behavior pattern.
Evaluation of Dermal Reaction:
Dermal reaction was observed daily for study period of 14 days.
Body weights:
Individual animal body weights were recorded pre-test (prior to administration of the test item), day 7 and at termination on day 14.
Gross Pathology:
Necropsy was performed on animals surviving at the end of the study. Macroscopic examination of all the orifices, cavities and tissues were made and the findings were recorded. All animals surviving the study period were sacrificed by the carbon dioxide asphyxiation technique (day 15).
Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed. - Statistics:
- No data
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Sex : Male
Group I -
All animals survived through the study period of 14 days.
Sex : Female
Group I -
All animals survived through the study period of 14 days. - Clinical signs:
- Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.
Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days. - Body weight:
- Sex : Male
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 9.03% and 18.46% respectively.
Sex : Female
Group I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 5.69% and 9.55% respectively. - Gross pathology:
- Gross pathological examination did not reveal any abnormalities in animals from 2000 mg/kg dose group.
- Other findings:
- - Other observations:
Evaluation of Dermal Reaction
Sex : Male
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days.
Sex : Female
Group I -
Animal treated at the dose level of 2000 mg/kg body weight did not result in any skin reaction during the study period of 14 days. - Interpretation of results:
- other: Not Classified
- Conclusions:
- It was concluded that the acute dermal median lethal dose (LD50) of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), when administered to male and female Sprague Dawley rats was found to be greater than 2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) does not classify as an acute dermal toxicant.
CLP Classification: “Unclassified”. - Executive summary:
The study now reported was designed and conducted to determine the acute dermal toxicity profile of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5)in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days.
Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), when administered to male and female Sprague Dawley rats was found to be greater than 2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) does not classify as an acute dermal toxicant. CLP Classification: “Unclassified”.
Reference
Table No. I
Summary of Clinical Signs of Toxicity and Mortality
Test System : Sprague Dawley Rat
Sex : Male
Group No. |
Dose mg/kg |
Observed Signs |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
I |
2000 |
No clinical signs observed |
5 |
1 - 5 |
Day 0 - Day 14 |
0/5 |
Sex : Female
Group No. |
Dose mg/kg |
Observed Signs |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
I |
2000 |
No clinical signs observed |
5 |
6 - 10 |
Day 0 - Day 14 |
0/5 |
Table No. II
Summary of Evaluation of Dermal Reaction
Test System : Sprague Dawley Rat
Sex : Male
Group No. |
Dose mg/kg |
Dermal Reaction |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
I |
2000 |
No dermal reaction observed |
5 |
1 - 5 |
Day 0 - Day 14 |
0/5 |
Sex : Female
Group No. |
Dose mg/kg |
Dermal Reaction |
Total Number of Animals |
Animal Nos. |
Period of signs in days From - to |
Mortality |
I |
2000 |
No dermal reaction observed |
5 |
6 - 10 |
Day 0 - Day 14 |
0/5 |
Table No.III
Mean Body Weight and Percent Body Weight Gain (g)
Test System : Sprague Dawley Rat
Sex : Male
Group No. |
Dose (mg/kg body weight) |
|
Body weight Day 0 |
Body weight Day 7 |
% body weight gain day 0-7 |
Body weight Day 14 |
% body weight gain day 7- 14 |
% body weight gain day 0- 14 |
I |
2000 |
Mean |
245.26 |
267.38 |
9.03 |
290.50 |
8.65 |
18.46 |
± SD |
5.06 |
4.63 |
0.64 |
4.65 |
0.40 |
0.95 |
Sex : Female
Group No. |
Dose (mg/kg body weight) |
|
Body weight Day 0 |
Body weight Day 7 |
% body weight gain day 0-7 |
Body weight Day 14 |
% body weight gain day 7- 14 |
% body weight gain day 0- 14 |
I |
2000 |
Mean |
218.46 |
230.88 |
5.69 |
239.32 |
3.66 |
9.55 |
± SD |
3.57 |
3.95 |
0.59 |
4.16 |
0.59 |
0.71 |
Table No.IV
Summary of Gross Pathological Findings
Test System : Sprague Dawley Rat
Sex : Male
Group No. |
Dose mg/kg |
Animal Numbers |
Animal Fate |
Gross Pathological Findings |
I |
2000 |
1 - 5 |
TS |
No abnormality detected |
Sex : Female
Group No. |
Dose mg/kg |
Animal Numbers |
Animal Fate |
Gross Pathological Findings |
I |
2000 |
6 - 10 |
TS |
No abnormality detected |
TS = Terminal Sacrifice
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- Data is of K1 reliability and is obtained from experimental study report.
Additional information
Acute
toxicity: oral
Different
experimental studies were reviewed for acute oral toxicity endpoint for
the test substance 4-(phenyldiazenyl)benzene-1,3-diamine and are
presented below as key and supporting studies:
The study now reported was designed and conducted to determine the acute oral toxicity profile of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) in Sprague Dawley rats. Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg resulted in reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing and no mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg resulted in reduced locomotor activity and ataxic gait with onset at 4 hours after the dosing and no mortality after the dosing. No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in polyurea, diarrhoea, reduced locomotor activity and ataxic gait with onset at 30 minutes to day 1 after the dosing. Two animals died on day 1 after the dosing. All animals from 300 mg/kg dose group survived and exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities in animals sacrificed terminally from 300 mg/kg and 2000 mg/kg dose groups. Gross pathological examination revealed distended stomach with test item coloured ingesta and small and large intestine with liquid test item coloured ingesta in found dead animals from 2000 mg/kg dose group. The acute oral LD50 (Cut-off value) of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) was 1000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), when administered via oral route in Sprague Dawley rats falls into the “Category 4 (300 – ≤ 2000)” criteria of CLP.
Supporting data were obtained from Initial submission report from National Technical Report library as follows:
Acute oral toxicity study was conducted on young adult Sprague Dawley rats using the test compound Solvent orange 3/ Calco Chrysoidine Y Base. Further to dose range finding study and the trial study, the dose range selected for the main study was 500, 813, 1323, 2152 and 3500 mg/Kg bw. Cage side observations, clinical signs and mortality was checked. On the basis of observations made,Solvent orange 3/ Calco Chrysoidine Y Baseshows an acute oral LD50 for male rats to be 2212 mg/kg bw with a 95% confidence interval of 1558 to 3859 mg/kg. The LD50 for females is to be 1037 mg/kg bw with a 95% confidence interval of 698 to 1540 mg/kg and the combined response (males and females) is 1532 mg/kg with a 95% confidence interval of 1192 to 1993 mg/kg.
Range finding acute oral toxicity study was conducted on young adult Sprague Dawley rats using the test compound Solvent orange 3/ Calco Chrysoidine Y Base. In the dose range finding study, the dosage level used was 500, 813, 1581, 2812 and 5000 mg/Kg. LD50 value was found out on the basis of mortality observed. On the basis of observations made,Solvent orange 3/ Calco Chrysoidine Y Bases hows an acute oral LD50 for male/female rats to be 1581 mg/kg bw.
Acute oral toxicity study was conducted on young adult Sprague Dawley rats using the test compound Solvent orange 3/ Calco® Chrysoidine Y Base. A trial study was conducted at a dosage level of 5000 mg/Kg bw.Cage side observations, clinical signs and mortality was checked. On the basis of observations made, Solvent orange 3/ Calco® Chrysoidine Y Base shows an acute oral LD100 for male/female rats to be 5000 mg/kg.
Based on the values from the above studies it can be concluded that the substance can be classified in acute category IV as per the criteria of CLP regulation.
Further supporting above experimental data was based on the QSAR prediction done using the Danish (Q)SAR Database, the LD50 was estimated to be 1100 mg/kg/d on rat for substance m-Phenylenediamine, 4(phenylazo)-. Thus based on this value it can be concluded that the substance can be classified in acute category IV as per the criteria of CLP regulation.
Data obtained from RTECS database also indicates the acute oral LD50 value of m-Phenylenediamine, 4(phenylazo)- as 1650 mg/kg in rat.
Thus, considering the key and various supporting studies for the substance 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), it was concluded that the substance is toxic via oral route and hence it can be classified in acute category IV as per the criteria of CLP regulation.
Acute
toxicity: inhalation
The
study need not be conducted because exposure of humans via inhalation is
not likely taking into account the vapour pressure of the substance
and/or the possibility of exposure to aerosols, particles or droplets of
an inhalable size.
Acute
toxicity: dermal
Experimental
data for the test substance 4-(phenylazo)benzene-1,3-diamine (CAS
495-54-5) and its structurally related substance 4-Aminodiphenylamine
(CAS 101-54-2) were reviewed for classification of the substance in
acute dermal category and are presented below:
The study now reported was designed and conducted to determine the acute dermal toxicity profile of4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5)in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5), when administered to male and female Sprague Dawley rats was found to be greater than 2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) does not classify as an acute dermal toxicant. CLP Classification: “Unclassified”.
24 hrs acute toxicity test was performed on rabbits to measure the toxicity potential of the structurally related substance 4-Aminodiphenylamine (CAS 101-54-2) via dermal route of application (as cited in OECD SIDS assessment report). No deaths occurred after a single 24-hour occlusive dermal application of 5000 mg of test substance/kg bw (applied as a paste, moistened with saline) to the clipped, intact skin of 5 male and 5 female rabbits. During the 14 day post-exposure observation period only a few animals showed decreased food consumption, and nasal and ocular discharge. Single occurrences of red and/or swollen eyes were observed. Necropsy findings were not different from controls. The dermal LD50 in rabbits is greater than 5000 mg/kg bw.
Thus,
considering the key study for target and supporting study for
structurally related substance. it can be concluded that the target
substance 4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) is not
toxic via dermal and hence is considered as Not classified as per the
criteria of CLP regulation.
Justification for classification or non-classification
Considering
the key studies, it can be concluded that the substance
4-(phenylazo)benzene-1,3-diamine (CAS No. 495-54-5) is toxic via oral
route and non toxic via dermal route and hence is
classified in Acute category IV
for oral route and Not classified for dermal route as per the criteria
of CLP regulation.
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