2-(4-aminoanilino)-5-nitrobenzenesulphonic acid

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

28 days subacute repeated dose oral toxicity study was performed to determine the oral toxic nature of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid. The study was performed using Wistar rats as per the OECD guideline no 407. 5 male and 5 female rats recieved feed at dosage of 0, 480, 2400 or 12000 mg/Kg containing an average daily substance intake of 0, 50, 243 or 1253 mg/Kg bw in male rats and 0, 47, 234 or 1191 mg/Kg bw in female rats. All animals were observed for clinical symtoms, mortality, hematological and clinical chemistry parameters, urinanalysis, and were subjected to gross and histopathological observations. All animals well tolerated the highest dose and did not show any signs at the highest dose level corresponding to 1253 mg/Kg bw for male rats and 1191 mg/Kg bw for female rats. No changes were noted in hematological and clinical chemistry parameters. Urinanalysis represented brown discoloration of urine in the highest dose group (1253 mg/Kg bw for males and 1191 mg/Kg bw for females). 2 male rats of 2400 mg/Kg bw feed group and all male rats of 12000 mg/Kg feed group exhibited ocherous kidneys. No cases of histopathological observations were made. On the basis of observations made, the No Observed Adverse Effect level for the test substance 4-nitro-4’-aminodiphenylamine-2-sulfonic acid is considered to be 1253 mg/Kg bw in male rats and 1191 mg/Kg bw in female rats.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary literature

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

Repeated dose oral toxicity study was performed to determine the toxic nature of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid upon repeated exposure by oral route

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material: 4-nitro-4’-aminodiphenylamine-2-sulfonic acid
- IUPAC name: 2-[(4-aminophenyl)amino]-5-nitrobenzenesulfonic acid
- Molecular formula: C12H11N3O5S
- Molecular weight: 309.301 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: 58.9% , 40.2% water
- Impurities: No data

Species:

rat

Strain:

Wistar

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: 6 weeks old
- 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

Route of administration:

oral: feed

Details on route of administration:

No data

Vehicle:

other: Feed

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test compound was mixed with feed (0, 480, 2400 or 12000 mg/Kg feed) to give an average daily intake of 0, 50, 243 or 1253 mg/Kg bw in male rats and 0, 47, 234 or 1191 mg/Kg bw in female rats

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle:
Male rats: 0, 50, 243 or 1253 mg/Kg bw
Female rats: 0, 47, 234 or 1191 mg/Kg bw
- Amount of vehicle (if gavage): 0, 480, 2400 or 12000 mg/Kg feed
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

28 days

Frequency of treatment:

Daily

Remarks:

Male rats: 0, 50, 243 or 1253 mg/Kg bw
Female rats: 0, 47, 234 or 1191 mg/Kg bw

No. of animals per sex per dose:

Total: 40
0 mg/Kg bw: 5 male and 5 female
50 mg/Kg bw: 5 males
243 mg/Kg w: 5 males
1253 mg/Kg bw: 5 males
47 mg/Kg bw: 5 females
234 mg/Kg bw: 5 females
1191 mg/Kg bw: 5 females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: The doses were selected on the basis of a preliminary toxicity study conducted on rats. The dosage level for the study was 2000 or 10000 mg/ Kg feed suring a period of 14 days. No changes in the body weight and food consumption were observed during the study. No unusual hematological findings were observed. Also the animals did not exhibit any macroscopic changes during the study. On this basis, the doses selected for the study were 0, 480, 2400 or 12000 mg/Kg feed containing an average daily intake of 0, 50, 243 or 1253 mg/Kg bw in male rats and 0, 47, 234 or 1191 mg/Kg bw in female rats
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data

Positive control:

No data

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Throughout the treatment period
- Cage side observations checked in table [No.?] were included. The animals were observed for any symptoms and mortality

DETAILED CLINICAL OBSERVATIONS: Not specified
- Time schedule: Not specified

BODY WEIGHT: Not specified
- Time schedule for examinations: Not specified

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: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

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: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations: Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Not specified
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined. Not specified

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Not specified
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined. Not specified

URINALYSIS: Yes
- Time schedule for collection of urine: Not specified
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined. the animals were checked for discoloration of urine

NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not specified

IMMUNOLOGY: Not specified
- Time schedule for examinations: Not specified
- How many animals: Not specified
- Dose groups that were examined: Not specified
- Parameters checked in table [No.?] were examined. Not specified

OTHER: Not specified

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, the animals were subjected to gross pathology findings

HISTOPATHOLOGY: Yes, the animals were subjected to histopathological findings

Other examinations:

No data

Statistics:

No data

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not specified

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:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

Clinical signs and mortality
Clinical signs: All animals tolerated the treatment without any symptoms even at the highest dosage (1253 mg/Kg bw for males and 1191 mg/Kg bw for females).
Mortality: No mortality was noted at the highest dosage (1253 mg/Kg bw for males and 1191 mg/Kg bw for females)

Body weight and weight gain: No data available

Food consumption and compound intake: No data available

Food efficiency: No data available

Water consumption and compound intake: No data available

Opthalmoscopic examination: No data available

Haematology: The hematological parameters remained unchanged during the study period

Clinical chemistry: The clinical chemistry parameters remained unchanged during the study period

Urinanalysis: Urine of the animals in the highest dose group (1253 mg/Kg bw for males and 1191 mg/Kg bw for females) showed brown discoloration. Urinary starus and sediments were not unusual

Neurobehaviour: No data available

Organ weights: No data available

Gross pathology: 2 male rats of 2400 mg/Kg bw dose group and all male rats of 12000 mg/Kg dose group exhibited ocherous kidneys

Histopathology: Histology revealed no cases of pathological findings.

Dose descriptor:

NOAEL

Effect level:

1 253 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant alterations were noted at the mentioned dose level

Dose descriptor:

NOAEL

Effect level:

1 191 mg/kg bw (total dose)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No significant alterations were noted at the mentioned dose level

Critical effects observed:

not specified

Conclusions:

The No Observed Adverse Effect level for the test substance 4-nitro-4’-aminodiphenylamine-2-sulfonic acid is considered to be 1253 mg/Kg bw in male rats and 1191 mg/Kg bw in female rats.

Executive summary:

28 days subacute repeated dose oral toxicity study was performed to determine the oral toxic nature of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid. The study was performed using Wistar rats as per the OECD guideline no 407. 5 male and 5 female rats recieved feed at dosage of 0, 480, 2400 or 12000 mg/Kg containing an average daily substance intake of 0, 50, 243 or 1253 mg/Kg bw in male rats and 0, 47, 234 or 1191 mg/Kg bw in female rats. All animals were observed for clinical symtoms, mortality, hematological and clinical chemistry parameters, urinanalysis, and were subjected to gross and histopathological observations. All animals well tolerated the highest dose and did not show any signs at the highest dose level corresponding to 1253 mg/Kg bw for male rats and 1191 mg/Kg bw for female rats. No changes were noted in hematological and clinical chemistry parameters. Urinanalysis represented brown discoloration of urine in the highest dose group (1253 mg/Kg bw for males and 1191 mg/Kg bw for females). 2 male rats of 2400 mg/Kg bw feed group and all male rats of 12000 mg/Kg feed group exhibited ocherous kidneys. No cases of histopathological observations were made. On the basis of observations made, the No Observed Adverse Effect level for the test substance 4-nitro-4’-aminodiphenylamine-2-sulfonic acid is considered to be 1253 mg/Kg bw in male rats and 1191 mg/Kg bw in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 253 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is from K4 secondary literature

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

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Data available for the target chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid was reviewed to determine its toxic nature upon repeated exposure by oral route. The summary is as mentioned below:

28 days subacute repeated dose oral toxicity study was performed to determine the oral toxic nature of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid. The study was performed using Wistar rats as per the OECD guideline no 407. 5 male and 5 female rats recieved feed at dosage of 0, 480, 2400 or 12000 mg/Kg containing an average daily substance intake of 0, 50, 243 or 1253 mg/Kg bw in male rats and 0, 47, 234 or 1191 mg/Kg bw in female rats. All animals were observed for clinical symtoms, mortality, hematological and clinical chemistry parameters, urinanalysis, and were subjected to gross and histopathological observations. All animals well tolerated the highest dose and did not show any signs at the highest dose level corresponding to 1253 mg/Kg bw for male rats and 1191 mg/Kg bw for female rats. No changes were noted in hematological and clinical chemistry parameters. Urinanalysis represented brown discoloration of urine in the highest dose group (1253 mg/Kg bw for males and 1191 mg/Kg bw for females). 2 male rats of 2400 mg/Kg bw feed group and all male rats of 12000 mg/Kg feed group exhibited ocherous kidneys. No cases of histopathological observations were made. On the basis of observations made, the No Observed Adverse Effect level for the test substance 4-nitro-4’-aminodiphenylamine-2-sulfonic acid is considered to be 1253 mg/Kg bw in male rats and 1191 mg/Kg bw in female rats.

Based on the data available for the target chemical, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid does not exhibit toxic nature upon repeated exosure by oral route. Hence the test chemical is likely to be non toxic.

Justification for classification or non-classification

Based on the data available for the target chemical, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid does not exhibit toxic nature upon repeated exosure by oral route. Hence the test chemical is likely to be non toxic.