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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
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 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5).
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): 2-Naphthalenesulfonic acid, 6-amino-
- Molecular formula (if other than submission substance): C10H9NO3S
- Molecular weight (if other than submission substance): 223.24g/mol
- Smiles notation (if other than submission substance): Nc1ccc2cc(S(O)(=O)=O)ccc2c1
- InChl (if other than submission substance): SEMRCUIXRUXGJX-UHFFFAOYSA-N
- Substance type: Organic
- Physical state: Solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Test Item: 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5)
- Source of test material: Sustainability Support Services (Europe) AB, Sweden
- Batch No. of test material: 7936
- Manufacturing Date: March; 2015
- Expiration date of the lot/batch: February; 2018
- 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: 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 1% aqueous Tween 80. 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).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: National Institute of Biosciences, Pune.
- Females (if applicable) 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 198.9 to 215.1 grams.
Body weights at the start :
Female
Mean : 205.26 g (= 100 %)
Minimum : 198.9 g (- 3.10 %)
Maximum : 215.1 g (+ 4.79 %)
Total No. of animals : 12
- 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 21.9 degree centigrade.
- Humidity (%): 56.3% to 59.8%.
- 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: 14-07-2017 to 02-08-2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% aqueous Tween 80
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg, 300 mg/kg, 2000 mg/kg and 2000 mg/kg
- Amount of vehicle (if gavage): No data available
- Justification for choice of vehicle:
1) One of the widely used suspending agent in the toxicological evaluations,
2) Test item was insoluble in water. Uniformly dispersed suspension of the test item was possible in 1% aqueous Tween 80.
3) Extremely safe with LD50 = 38 g/kg body weight.
- Lot/batch no. (if required): No data available
- Purity: No data available

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.

DOSAGE PREPARATION (if unusual): No data available

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No data available
Doses:
Dose Group I : 300 mg/kg
Dose Group I : 300 mg/kg
Dose Group II : 2000 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 at the end of the study period on day 15. 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.

Histopathology:
No gross abnormalities were observed in animals sacrificed terminally hence, no histopathology was performed.

Statistics:
No data

Results and discussion

Preliminary study:
no data
Effect levels
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was was observed.
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.

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: All animals survived through the study period of 14 days.

Group II
Step II :
Animals treated at the dose level of 2000 mg/kg body weight: All animals survived through the study period of 14 days.
Clinical signs:
Group I
Step I :
Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.

Group I
Step II :
Animals treated at the dose level of 300 mg/kg body weight did not result in any signs of toxicity during the study period of 14 days.

Group II
Step I :
Animals 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.
Group II
Step II :
Animals 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:
Group I
Step I (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.40% and 14.01% respectively.

Group I
Step II (300 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.46% and 12.23% respectively.

Group II
Step I (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.19% and 12.06% respectively.

Group II
Step II (2000 mg/kg) - Percent body weight gain after 7 days and 14 days was found to be 6.08% and 11.58% respectively.
Gross pathology:
Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.
Other findings:
No data available

Any other information on results incl. tables

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

No clinical signs observed

3

1,2,3

Day 0 - Day 14

0/3

 

 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

No clinical signs observed

3

4,5,6

Day 0 - Day 14

0/3

 

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

No clinical signs observed

3

7,8,9

Day 0 - Day 14

0/3

 

Group II :

Step

No.

Dose mg/kg

Observed Signs

Total Number of

Animals

Animal Nos.

Period of signs in days

From - to

Mortality

II

2000

No clinical signs observed

3

10,11,

12

Day 0 - Day 14

0/3

 

 

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

200.10

212.90

6.40

228.13

7.16

14.01

± SD

1.51

2.43

0.67

2.40

0.28

0.47

 

 

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

205.13

218.37

6.46

230.20

5.42

12.23

± SD

3.79

2.60

0.70

1.77

0.55

1.26

 

 

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

207.07

219.90

6.19

232.03

5.53

12.06

± SD

2.87

4.60

0.92

3.35

0.69

0.54

 

 

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

II

2000

Mean

208.73

221.43

6.08

232.83

5.18

11.58

± SD

6.67

7.14

0.11

4.66

1.49

1.59

 

 

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 - 9

TS

No abnormality detected

 

 Group II :

Step No.

Dose

mg/kg

Animal Numbers

Animal Fate

Gross Pathological Findings

II

2000

10 - 12

TS

No abnormality detected

                      

TS = Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Conclusions:
Under the condition of the study, the acute oral LD50 (Cut-off value) of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) was 5000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5), when administered via oral route in Sprague Dawley rats falls into the “Category Unclassified” criteria of CLP.
Executive summary:

the acute oral toxicity profile of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5)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 did not result in any signs of toxicity and 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 did not result in any signs of toxicity and 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 did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, additional three female animals were treated with the higher dose of  2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing.Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. The acute oral LD50 (Cut-off value) of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) was 5000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5), when administered via oral route in Sprague Dawley rats falls into the “Category Unclassified” criteria of CLP.