Registration Dossier

Administrative data

Description of key information

The substance do not show any short term toxicity effect on any of the route of exposure that is oral, dermal and inhalation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Age : 7 to 9 weeks
Sex : Female, nulliparous and non pregnant. It has been observed that females are generally more sensitive than males to toxic effects
Body weight range : 200±20g
Identification : By cage tag and corresponding colour body marking
Acclimatization : One week in experimental room after veterinary examination.
Randomization : After acclimation and veterinary examination randomly selected in groups of three females.
Nutritional conditions : Fasted overnight prior to treatment. Food was offered three hours after dosing.
Route of administration:
oral: drinking water
Vehicle:
water
Remarks:
distilled water
Details on oral exposure:
The toxicity of the 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid following oral administration was assessed. The test drug was given orally via oral cannula at the dose level 2000 mg/kg b.wt in Group-II & Group III respectively. Whereas, distilled water was given in same manner as test group(Group I). The rats were observed for incidence of mortality and signs of intoxication for 14 days after the administration of test article. The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment). Necropsy was carried out on all the animals which died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.
Doses:
2000 mg/kg b.wt
No. of animals per sex per dose:
Three female rats were used per step for each dose level.
Control animals:
yes
Details on study design:
The test compound was administered by oral route by using of oral cannula at the dose volume of 10 ml/kg b.wt. The treated animals were closely observed for clinical signs of intoxication, first 4 hours and every 1 hrs interval for 24 hrs after dosing and thereafter twice a day for 14 days. All the rats were observed at least twice daily to observe any clinical signs or behavioral changes. The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: non toxic in wistar albino rats
Mortality:
Wistar albino rats treated with the test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid did not produce any mortality throughout the period of observation.
Clinical signs:
The test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid did not show any clinical signs of toxicity at the tested dose level of 2000 mg/kg b.wt throughout the period of observation.
Body weight:
All the animals treated with 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid at the dose level of 2000 mg/kg b.wt showed normal gain in body weight as compared to control group .
Gross pathology:
Pathology
1.Necropsy
Necropsy was carried out on all the animals that died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.
2.Histopathological study
The organ showing gross pathological change during necropsy subjected for histopathological study.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
From the result obtained from present investigation it can be concluded that the test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid is acutely non toxic upto the tested dose level of 2000 mg/kg b.wt in wistar albino rats when applied by oral route.
The acute oral LD50 of test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid found to be more than 2000 mg/kg b.wt.
Executive summary:

Body weights

All the animals treated with the substance, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid, at the dose level of 2000 mg/kg b.wt showed normal gain in body weight as compared to control group. 

 

MORTALITY

Wistar albino rats treated with the test substance did not produce any mortality throughout the period of observation.

 

CLINICAL SIGNS

The test compound, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid, did not show any clinical signs of toxicity at the tested dose level of 2000 mg/kg b.wt throughout the period of observation.

 

NECROPSY FINDING

A.     EXTERNAL

         i.   Skin-Skin and hair coat was observed wet.

        ii.   All external orifices-Normal   

 B.  INTERNAL

I. Subcutaneous- No change was observed.

ii. Superficial and deep lymph nodes-No change in mesenteric lymph node.

 

ABDOMINAL CAVITY

i.          Opening and general examination-In the abdominal cavity all the organs were present in normal position.

ii.         Spleen-Normal upto highest tested dose level 2000 mg/kg b.wt.

iii.       Digestive system-No gross changes were observed in stomach and intestine upto highest tested dose level 2000 mg/kg b.wt.

iv.       Liver and biliary ducts-No gross pathological changes were observed

v.        Excretory system-No gross pathological changes were observed upto highest tested dose level 2000 mg/kg b.wt.

vi.       Adrenal-Observed normal.

vii.     Male/female genital organs –Showed normal colour, consistency and no inflammatory changes upto highest tested dose level 2000 mg/kg b.wt.

 

THORACIC CAVITY

i.                    Opening and general examination-Thoracic cavity was found to be normal without any fluid, mucous or blood etc.

ii.                  Lungs-observed normal.

iii.                 Heart-No changes were observed in color and consistency. Heart found normal upto highest tested dose level 2000 mg/kg b.wt.

iv.                Thyroid-Normal in shape, size and surface upto highest tested dose level 2000 mg/kg b.wt.

 

CRANIAL CAVITY- Brain-Normal in shape and size.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
K1 level data obtained by OECD testing

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Age : 8 to 10 weeks
Sex : Male and female
Body weight range : 200±20g
Identification : By cage tag and corresponding colour body marking
Acclimatization : The healthy wistar albino rats selected for study acclimatized to standard laboratory condition for period of one week under close Veterinary supervision.
Randomization : After acclimation and veterinary examination randomly selected in groups of three females.
Randomization: After acclimation and Veterinary examination all the animals randomly divided into two groups and each group having five male and five female rats.
Nutritional conditions: Animals were fasted overnight prior to test and food was offered three hours after dosing.
Type of coverage:
open
Vehicle:
water
Remarks:
distilled water
Details on dermal exposure:
The test drug 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid applied dermally under impervious gauze at the dose level of 2000 mg/kg b.wt in Group-I, II respectively. The test compound held in contact for period of 24 hrs. After 24 hrs, test compound was removed and wash with luke warm water and observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals which was died during the study or were sacrificed at termination of the study.
Duration of exposure:
24hrs.
Doses:
2000 mg/kg bwt
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
The test substance was applied uniformly over an exposed area of skin. The test compound was held in contact with the skin with an impervious dressing secured in place with an adhesive tape. The animals were then housed individually in cages with a collar around the neck in order to avoid the ingestion of the test compound. After 24 hours, the dressing was removed and the site of application was cleaned with lukewarm water wiping the test compound.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
dissolved
Remarks on result:
other: non toxic in wistar albino rats
Mortality:
The test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid did not produce any mortality at the tested dose level of 2000 mg/kg b.wt in wistar albino rats throughout the period of observation.
Clinical signs:
The test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid did not elicit any clinical signs of toxicity entire the observation period. No skin reaction was observed after 24th hrs. of patch removal.
Body weight:
The body weight of animals treated with test compound observed on days 7th 14th showed normal gain in body as compared to day 0 (pre-treatment)
Gross pathology:
Necropsy
Necropsy was carried out on all the animals that died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
From the result obtained from present investigation it can be concluded that the test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid is acutely non toxic upto the tested dose level of 2000 mg/kg b.wt in wistar albino rats when applied by dermal route. The acute dermal LD50 of test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid observed to be more than 2000 mg/kg b.wt.
Executive summary:

Mortality:

The test compound, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid,did not produce any mortality at the tested dose level of 2000 mg/kg b.wt in Wistar albino rats throughout the period of observation.

 

Clinical signs:

The test compound, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid,did not elicit any clinical signs of toxicity entire the observation period. No skin reaction was observed after 24thhrs. of patch removal.

 

Body weight:

The body weight of animals treated with test compound observed on days 7th& 14thshowed normal gain in body as compared to day 0 (pre-treatment) 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
K1 level data obtained by OECD testing

Additional information

Acute Oral toxicity:

All the animals treated with the substance, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid, at the dose level of 2000 mg/kg b.wt showed normal gain in body weight as compared to control group. Moreover Wistar albino rats treated with the test substance did not produce any mortality throughout the period of observation.

 

Regarding the clinical signs, the test compound, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid, did not show any clinical signs of toxicity at the tested dose level of 2000 mg/kg b.wt throughout the period of observation. Also the necropsy finding has been normal as mentioned below;

NECROPSY FINDING

A.     EXTERNAL

         i.   Skin-Skin and hair coat was observed wet.

        ii.   All external orifices-Normal   

 B.  INTERNAL

I. Subcutaneous- No change was observed.

ii. Superficial and deep lymph nodes-No change in mesenteric lymph node.

ABDOMINAL CAVITY

i.          Opening and general examination-In the abdominal cavity all the organs were present in normal position.

ii.         Spleen-Normal upto highest tested dose level 2000 mg/kg b.wt.

iii.       Digestive system-No gross changes were observed in stomach and intestine upto highest tested dose level 2000 mg/kg b.wt.

iv.       Liver and biliary ducts-No gross pathological changes were observed

v.        Excretory system-No gross pathological changes were observed upto highest tested dose level 2000 mg/kg b.wt.

vi.       Adrenal-Observed normal.

vii.     Male/female genital organs –Showed normal colour, consistency and no inflammatory changes upto highest tested dose level 2000 mg/kg b.wt.

THORACIC CAVITY

i.                    Opening and general examination-Thoracic cavity was found to be normal without any fluid, mucous or blood etc.

ii.                  Lungs-observed normal.

iii.                 Heart-No changes were observed in color and consistency. Heart found normal upto highest tested dose level 2000 mg/kg b.wt.

iv.                Thyroid-Normal in shape, size and surface upto highest tested dose level 2000 mg/kg b.wt.

 

CRANIAL CAVITY- Brain-Normal in shape and size.

Acute dermal Toxicity :

The test compound, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid,did not produce any mortality at the tested dose level of 2000 mg/kg b.wt in Wistar albino rats throughout the period of observation. The test compound, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid,did not elicit any clinical signs of toxicity entire the observation period. No skin reaction was observed after 24thhrs. of patch removal. Moreover, the body weight of animals treated with test compound observed on days 7th& 14thshowed normal gain in body as compared to day 0 (pre-treatment).

Acute inhalation toxicity :

In accordance with column 2 of Annex VIII, this end point was considered for waiver since given the very low vapour pressure of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid; exposure of humans via inhalation is highly unlikely and their is negligible possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – oral endpoint

From the result obtained from present investigation it  can be concluded that the test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid is acutely non toxic upto the tested dose level of 2000 mg/kg b.wt in wistar albino rats when applied by oral route.

The acute oral LD50 of test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid found to be more than 2000 mg/kg b.wt.

Justification for selection of acute toxicity – inhalation endpoint

In accordance with column 2 of Annex VIII, this end point was considered for waiver since given the very low vapour pressure of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid; exposure of humans via inhalation is highly unlikely and their is negligible possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint

From the result obtained from present investigation it  can be concluded that the test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid is acutely non toxic upto the tested dose level of 2000 mg/kg b.wt in wistar albino rats when applied by dermal route. The acute dermal LD50 of test compound 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid observed to be more than 2000 mg/kg b.wt.

Justification for classification or non-classification

Since the substance, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid, do not show any short term toxicity effect on any of the route of exposure that is oral, dermal and inhalation. So, it cannot be considered for classification as per the C&L criteria.