Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate

Acute Toxicity: oral

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

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:

The objective of this acute oral toxicity study was to assess the toxicological profile of the test item when administered to rats by a single oral gavage.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate

EC Number:

220-491-7

EC Name:

Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate

Cas Number:

2783-94-0

Molecular formula:

C16H12N2O7S2.2Na

IUPAC Name:

disodium 6-hydroxy-5-[(4-sulfonatophenyl)diazenyl]naphthalene-2-sulfonate

Test material form:

solid

Details on test material:

- Name of test material: disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate
- Molecular formula: C16H12N2O7S2.2Na
- Molecular weight: 454.38
- Substance type: organic
- Physical state: solid
-Purity : 91%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Vivo Bio Tech Ltd. Telangana
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 10 Weeks
- Weight at study initiation: 159.10 g to 169.08 g
- Fasting period before study: Rats were fasted overnight
- Identification:By rat accession number. Identification of individual rats was by cage card and turmeric colour body markings. The rat accession number was allotted during the course of the study. The temporary body marking during acclimatization period was done with crystal violet.
- Housing:Rats were housed individually in standard polysulfone cages
(Size: approximately L 425 x B 266 x H 185 mm), with stainless steel top grill having facilities for pelleted food and drinking water in polycarbonate bottle. Additionally, polycarbonate rat huts were placed inside the cage as an enrichment object and were changed along with the cage once a week
- Diet (e.g. ad libitum): Rat & Mice pellet feed, manufactured by Krishna Valley Agro Tech LLP, MIDC Kupwad block, Sangli, Maharashtra, was provided to animals
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd, Mumbai 400 001, India, was provided to animals in polycarbonate bottles with stainless steel sipper tubes
- Acclimation period:After physical examination for good health and suitability for experiment, the animals were acclimatized five days for G1-FTS and ten days for G1-STS before treatment. Animals were observed once daily during acclimatization period. Females were nulliparous and non-pregnant

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 59 to 67%,
- Air changes (per hr): air conditioned with adequate fresh air supply (12.4 air changes/hour)
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.

IN-LIFE DATES: From:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Concentration in vehicle:2000 mg/kg

Doses:

G1(FTS) -2000 mg/kg
G1(STS) - 2000 mg/kg
G2(FTS) - 2000 mg/kg

No. of animals per sex per dose:

G1(FTS) - 2000 mg/kg - 3
G1(STS) - 2000mg/kg - 3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At each step, the animals were observed five times on test day 1 (day of administration) i.e. at 30 minutes and four times at hourly intervals and once daily during days 2 to 15 post administration.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs and pre-terminal deaths: Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern. Attention was directed to the observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma and all observed clinical signs were recorded.
Body weights: The body weights were recorded on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration).
Gross Pathology: The rats surviving to the end of the observation period were euthanised by using isoflurane anaesthesia and subjected to detailed necropsy. Gross pathological findings were recorded and reported. Microscopic examination was not carried out as no gross pathological changes were observed.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: not other details available

Mortality:

G1(FTS) - 2000 mg/kg - No pre-terminal deaths were observed
G1(STS) - 2000 mg/kg - No pre-terminal deaths were observed

Clinical signs:

other: No changes observed

Gross pathology:

There were no gross pathological changes at necropsy.

Other findings:

not specified

Any other information on results incl. tables

TABLE 1.      Body weight, body weight change and pre-terminal deaths

Group and Dose (mg/kg body weight)	Rat No.	Sex	Body weight (g)						Day of Death  (Time of Death)	No. dead/  No. tested	Pre-terminal deaths (%)
			Initial (Day 1)	8^thday	Weight change (day 8 – Initial)	15^thday	Weight change           (day 15 – Initial)	At Death
G1 (FTS) 2000	Rm8767	F	169.08	190.09	21.01	201.69	32.61	NA	NA	0/3	0
	Rm8768	F	162.00	181.86	19.86	193.26	31.26	NA	NA
	Rm8769	F	159.10	173.41	14.31	185.02	25.92	NA	NA
G1 (STS) 2000	Rm8770	F	163.59	182.31	18.72	195.91	32.32	NA	NA	0/3	0
	Rm8771	F	159.85	177.63	17.78	182.51	22.66	NA	NA
	Rm8772	F	160.86	185.03	24.17	187.15	26.29	NA	NA

 F: Female        FTS: First Treatment Step            STS: Second Treatment Step              NA: Not Applicable           

 

APPENDIX 1.      Individual clinical signs, dose administration and necropsy findings

Group and Dose (mg/kg body weight) Date and time of administration Rat No. Sex Body weight (Day 1) (g) Total volume administered (mL) Day of observation Day 1 30 min 1hour 2 hours 3 hours 4 hours G1 (FTS) 2000     05 April 2018 and 10:35 AM to 10:37 AM Rm8767 F 169.08 1.7 N N N N N Rm8768 F 162.00 1.6 N N N N N Rm8769 F 159.10 1.6 N N N N N

F: Female            FTS: First treatment step              N: Normal            min: minutes         mg: milligrams            kg: kilograms       

mL: millilitre         055 (b): Recumbent;            043 (1): Ataxia – slight;              NAD: No Abnormality Detected 

APPENDIX 2 contd. Individual clinical signs, dose administration and necropsy findings                 

 

Group and Dose (mg/kg body weight)	Date and time of administration	Rat No.	Sex	Body weight (Day 1) (g)	Total volume administered (mL)	Day of observation
						Day 1
						30 min	1hour	2 hours	3 hours	4 hours
G1 (STS) 300	13 April 2018 and 11:30 AM to 11:33 AM	Rm8898	F	209.31	0.06	N	N	N	N	N
		Rm8899	F	214.86	0.06	N	N	N	N	N
		Rm8900	F	193.13	0.06	043 (1)	043 (1)	043 (1)	043 (1)	N

Group and Dose (mg/kg body weight)

Rat No.

Sex

Day of observation

Necropsy Findings

2

3

4

5

6

7

8

9

10

11

12

13

14

15

G1 (FTS) 2000

Rm8767

F

N 161(14

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rm8768

F

N 161(14

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rm8769

F

N 161(14

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

F: Female            FTS: First treatment step              N: Normal            min: minutes         mg: milligrams            kg: kilograms       

mL: millilitre         NAD: No Abnormality Detected  161(14): Faecal colour- yellowish to orange

APPENDIX 2 contd. Individual clinical signs, dose administration and necropsy findings                 

 

Group and Dose (mg/kg body weight)	Date and time of administration	Rat No.	Sex	Body weight (Day 1) (g)	Total volume administered (mL)	Day of observation
						Day 1
						30 min	1hour	2 hours	3 hours	4 hours
G1 (STS) 2000	10 April 2018 and 10:34 AM to 10:39 AM	Rm8770	F	163.59	1.6	N	N	N	N	N
		Rm8771	F	159.85	1.6	N	N	N	N	N
		Rm8772	F	160.86	1.6	N	N	N	N	N

Group and Dose (mg/kg body weight)

Rat No.

Sex

Day of observation

Necropsy Findings

2

3

4

5

6

7

8

9

10

11

12

13

14

15

G1 (STS) 2000

Rm8770

F

N 161(14

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rm8771

F

N 161(14

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

Rm8772

F

N 161(14

N

N

N

N

N

N

N

N

N

N

N

N

N

NAD

F: Female         STS: Second treatment step             N: Normal              min: minutes       mg: milligrams                      kg: kilograms             

mL: millilitre     NAD: No Abnormality Detected      161(14): Faecal colour- yellowish to orange

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the condition of the study, the acute oral LD50 (Cut-off value) of Neelicol Sunset Yellow FCF (CAS No. 2783-94-0) was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Neelicol Sunset Yellow FCF (CAS No. 2783-94-0), when administered via oral route in Wistar rats.

Executive summary:

The acute oral toxicity study withNeelicol Sunset YellowFCF[KZ1] in Wistar rats was conducted to assess the toxicological profile of the chemical Neelicol Sunset Yellow FCF(CAS No.2783 -94 -0). The dose formulation was prepared by using Milli-Q water and administered as a single oral gavage to overnight fasted (16 to 19 hours) three female rats (G1-FTS) at the dose of 2000 mg/kg body weight. There were no clinical signs of toxicity and pre-terminal deaths. Hence, a confirmatory test was done at 2000 mg/kg body weight (G1-STS) with three additional female rats as per Annex 2d of the guideline OECD 423. There were no clinical signs of toxicity and pre-terminal deaths. Based on the scheme - Annex 2d of the guideline OECD 423, further dosing was stopped.The rats were observed for mortality and clinical signs for 14 days post treatment. Body weights were recorded prior to dosing on day 1 and again on days 8 and 15. Necropsy was performed for all the rats at termination. All survived rats gained weight during experimental period. There were no gross pathological changes at necropsy.Based on the results of the present study, the test item,
Neelicol Sunset Yellow FCF, the LD₅₀is >2000-5000 mg/kg body weight or Unclassified as per LD₅₀cut-off value.