p-[4,5-dihydro-4-[[2-methoxy-5-methyl-4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulphonic acid

Acute Toxicity: oral

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 report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

Acute Oral Toxicity of Aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex in Rat

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex

EC Number:

271-524-7

EC Name:

Aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex

Cas Number:

68583-95-9

Molecular formula:

C18H16AlN2O8S2

IUPAC Name:

aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex
- Substance type: Organic
- Physical state: Solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source of test material: Sustainability Support Services (Europe) AB
- Lot/batch No. of test material: FG/15-16/1018
- Expiration date of the lot/batch: June, 2023
- Purity test date: No data

RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity: No data
- Specific activity: No data
- Locations of the label: No data
- Expiration date of radiochemical substance: No data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Test Item was stored at ambient temperature.
- Stability under test conditions: No data
- Solubility and stability of the test substance in the solvent/vehicle: No data
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was suspended in distilled water.
- Preliminary purification step (if any): No data
- Final dilution of a dissolved solid, stock liquid or gel: The formulation was prepared fresh on the day of dosing. The test item was administered in the dose volume of 10 ml/kg body weight.
- Final preparation of a solid: No data

FORM AS APPLIED IN THE TEST (if different from that of starting material) : No data

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 or test system 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.
- Weight at study initiation : The weight were within ± 20% of the mean weight of any animal used for dosing. Body weight range was 197.4 to 205.5 grams.
Body weights at the start :
Female
Mean : 201.90 g (= 100 %)
Minimum : 197.4 g (- 2.23 %)
Maximum : 205.5 g (+ 1.78 %)
Total No. of animals : 12
- 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): Room temperature was maintained at 20.6 to 23.2 degree centigrade
- Humidity (%): Room humidity was maintained at 54.2% to 58.6%.
- Air changes (per hr): The animal room was independently provided with at least ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters.
- Photoperiod (hrs dark / hrs light): An artificial light and dark cycle of 12 hours each was provided to the room.

IN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: No data
- 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: The test item was administered in the dose volume of 10 ml/kg body weight.

DOSAGE PREPARATION (if unusual): No data
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 II : 2000 mg/kg

No. of animals per sex per dose:

Three females were used at each step.

Control animals:

yes

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.

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.

Statistics:

No data

Results and discussion

Preliminary study:

No data

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality observed

Effect levels 2

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

Administration of the test item at 300 mg/kg did not result in any 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, hence 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.

Clinical signs:

other: 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 an

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

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 - 3	0 to 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 - 6	0 to 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 - 9	0 to 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 - 12	0 to 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	204.07	215.00	5.35	229.80	6.89	12.61
		± SD	1.63	3.06	0.72	2.88	0.38	0.52

 

 

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	203.23	213.67	5.13	230.30	7.79	13.32
		± SD	1.21	2.60	0.93	2.25	0.37	0.93

 

 

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	201.13	214.37	6.58	231.50	7.99	15.09
		± SD	1.45	1.90	0.84	3.18	1.37	0.76

 

 

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	199.17	212.57	6.74	229.20	7.83	15.09
		± SD	1.55	2.30	1.87	2.11	0.18	1.82

 

 

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:

Category 5 based on GHS criteria

Conclusions:

The lethal concentration (LD50) value for acute oral toxicity test was considered to be >2000 mg/kg bw ,when 6 females Sprague Dawley rats were treated with Aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (68583-95-9)orally via gavage.

Executive summary:

Acute oral toxicity study was done in 6 femaleSprague Dawley rats using test material Aluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (68583-95-9)according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).Distill water was used as vehicle. Female rats of the age of approximately 8 to 12 weeks old were used.Initial body weight were within ± 20% of the mean weight of any animal used for dosing. Body weight range was 197.4 to 205.5 grams.Animals wereapproximatelyfasted for16 hours or more.The rats were housed in polycarbonate cages.Rodent feed and water was provided ad libitum.Animals were acclimatized for 5 days. Room temperature was maintained at 20.6 to 23.2 degree centigrade.Room humidity was maintained at 54.2% to 58.6%.The animal room was independently provided with at least ten to fifteen air changes per hour of 100% fresh air that had been passed through the HEPA filters.An artificial light and dark cycle of 12 hours each was provided to the room.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, hence 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.Nomortality was observed at dose 300 mg/kg bw and2000 mg/kg bw.Hence,LD50 value was considered to be >2000 mg/kg bw,when rats were treated withAluminium, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (68583-95-9)orally via gavage.