Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate

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

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate

EC Number:

241-409-6

EC Name:

Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate

Cas Number:

17372-87-1

Molecular formula:

C20H6Br4Na2O5

IUPAC Name:

disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate

Details on test material:

- IUPAC Name: Disodium 2-(2,4,5,7-tetrabromo-6-oxido-3-oxo-3H-xanthen-9-yl)benzoate
- InChI: 1S/C20H8Br4O5.2Na/c21-11-5-9-13(7-3-1-2-4-8(7)20(27)28)10-6-12(22)17(26)15(24)19(10)29-18(9)14(23)16(11)25;;/h1-6,25H,(H,27,28);;/q;2*+1/p-2
- Smiles: c1(c2c(oc3c1cc(Br)c(c3Br)[O-])c(c(=O)c(c2)Br)Br)c1c(cccc1)C(=O)[O-].[Na+].[Na+]
- Molecular formula :C20H6Br4Na2O5
- Molecular weight :691.858 g/mol
- Substance type:Organic
- Physical state:Brownish powder
- Purity as per Certificate of Analysis:95.022 %
- Lot No.:L168831601
- Manufactured date:JAN-2016
- Retest date:DEC-2020
- pH:6.55 at 26 °C
- Density:Pour density :0.781 g/cm3 @ 27.05 °C; Tap density :0.97 g/cm3 @ 27.05 °C
- Storage conditions:Ambient (+15 to +25 °C )

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Geniron Biolabs Pvt. Ltd, Bengaluru
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11 to 12 Weeks
- Weight at study initiation: 169.70 g to 189.74 g
- 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.
- Fasting period before study: rats were fasted for approximately 17 hours.
- Housing:Rats were housed individually in standard polysulfone cages (Size: L 425 x B 266 x H 185 mm), with stainless steel top grill
- Diet (e.g. ad libitum): Rat & Mice pellet feed, ad libitum
- 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, Mumbai, ad libitum
- Acclimation period: The animals were acclimatized six days for G1-FTS and eleven days for G1-STS before treatment. Animals were observed once daily during acclimatization period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 24°C
- Humidity (%): 56 to 67%
- Air changes (per hr): air conditioned with adequate fresh air supply (12.9 air changes/hour)
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.

IN-LIFE DATES: From: 22 June 2018 To: 31 August 2018

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Milli-Q water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg body weight (G1 First and second treatment steps)
- Amount of vehicle (if gavage):10 mL/kg

DOSAGE PREPARATION (if unusual): A required quantity of test item was weighed in beaker and small volume of the Milli-Q water was added and mixed by using glass rod and transferred to a measuring cylinder. The beaker was rinsed with vehicle and all the rinsing was quantitatively transferred into the measuring cylinder. The final volume was made up to the mark with Milli-Q water to get the desired test item concentration of 200 mg/mL. The prepared dose formulation was transferred to the dedicated labeled beaker. Preparations were made prior to dosing.

Doses:

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

No. of animals per sex per dose:

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

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and pre-terminal deaths - 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. 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).

- Necropsy of survivors performed: yes, 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

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

G1 - [2000 mg/kg body weight - Treatment (FTS and STS)]: There were no pre-terminal deaths were observed.

Clinical signs:

other: G1 - [2000 mg/kg body weight - Treatment (FTS and STS)]: There were no clinical signs observed in any of the rats, except reddish brown faeces on days 2 and 3 of the observation period which is due to the colour of the test item.

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

Body weight (g)

No. dead/

Pre-

Dose

Rat

Weight

Weight

Day of Death

terminal

(mg/kg

No.

Sex

Initial

th

change

th

change

At

(Time of Death)

No.

deaths

body weight)

(Day 1)

8 day

(day 8 –

15 day

(day 15

Death

tested

(%)

Initial)

– Initial)

G1

Rw211

F

176.39

181.69

5.3

186.17

9.78

NA

NA

(FTS)

Rw212

F

178.59

181.85

3.26

187.22

8.63

NA

NA

0/3

0

2000

Rw213

F

183.89

195.05

11.16

199.81

15.92

NA

NA

G1

Rw214

F

176.99

184.00

7.01

187.32

10.33

NA

NA

(STS)

Rw215

F

169.70

171.39

1.69

180.53

10.83

NA

NA

0/3

0

2000

Rw216

F

189.74

196.18

6.44

197.84

8.1

NA

NA

F: Female

FTS: First Treatment Step

STS: Second Treatment Step

NA: Not Applicable   0: No deaths

 

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

Based on the results of the present study, the LD50 value of the given test chemical is >2000 mg/kg bw. Thus, the test item is not classified for acute oral toxicity. CLP criteria "Not Classified".

Executive summary:

The acute oral toxicity study was conducted to assess the toxicological profile of the test item as per OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method) in Wistar rats.

The dose formulation was prepared by using Milli-Q water and administered as a single oral gavage to overnight fasted (approximately 17 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, the dose 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 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 LD50 value of the given test chemical is >2000 mg/kg bw. Thus, the test item is not classified for acute oral toxicity. CLP criteria "Not Classified".