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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:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexasodium 2,2'-[vinylenebis[(3-sulphonato-4,1-phenylene)imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis(benzene-1,4-disulphonate)
EC Number:
255-217-5
EC Name:
Hexasodium 2,2'-[vinylenebis[(3-sulphonato-4,1-phenylene)imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis(benzene-1,4-disulphonate)
Cas Number:
41098-56-0
Molecular formula:
C40H44N12O18S6.6Na
IUPAC Name:
hexasodium 2-{[4-(diethylamino)-6-({4-[(E)-2-(4-{[4-(diethylamino)-6-[(2,5-disulfonatophenyl)amino]-1,3,5-triazin-2-yl]amino}-2-sulfonatophenyl)ethenyl]-3-sulfonatophenyl}amino)-1,3,5-triazin-2-yl]amino}benzene-1,4-disulfonate
Constituent 2
Reference substance name:
“Hexasodium 2,2’-[vinylenebis[(3-sulphonato-4,1-phenylene) imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis (benzene-1,4-disulphonate)
IUPAC Name:
“Hexasodium 2,2’-[vinylenebis[(3-sulphonato-4,1-phenylene) imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis (benzene-1,4-disulphonate)
Test material form:
liquid
Details on test material:
- Name of the test chemical: Hexasodium 2,2'-(vinylenebis((3-sulphonato-4,1-phenylene)imino(6-(diethylamino)-1,3,5-triazine-4,2-diyl)imino))bis(benzene-1,4-disulphonate)
- Molceular formula: C40H38N12O18S6.6Na
- Molecular weight: 1305.1422 g/mol
- Smiles: CCN(CC)c1nc(nc(n1)Nc2cc(ccc2S(=O)(=O)[O-])S(=O)(=O)[O-])Nc3ccc(c(c3)S(=O)(=O)[O-])/C=C/c4ccc(cc4S(=O)(=O)[O-])Nc5nc(nc(n5)N(CC)CC)Nc6cc(ccc6S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Species :Rattus norvegicus (Rat)
Strain :Wistar
Number and Sex:Six Females
Supplier / Source: In-house animals, bred at Animal House, sa-FORD.CPCSEA Registration No. 1256/bc/09/CPCSEA.
Health Status :Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
Body weight of animals:Minimum: 149 g Maximum: 161 g (Individual body weights were within ± 20 % prior to treatment after overnight fasting)
Age : 8- 11 weeks at the time of dosing.
Acclimatisation:Animal nos. 1-3 were acclimatized for 6 days and 4-6 for 10 days, prior to administration of the test item.
Identification :The animals were marked temporarily on tail, permanently on toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number experimental start and completion date.

Diet :All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No.: 400010 and 400011.
Bedding :All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) SPAR – 27 /2014.
Water : Aqua guard filtered tap water was provided ad libitum via drinking bottles.
Husbandry :The animals were housed individually in polycarbonate cages.
Room Sanitation:The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
Cages and water bottle:All the cages and water bottles were changed at least twice every week
Temperature :Minimum: 19.40 °C Maximum: 22.10 °C
Relative humidity:Minimum: 46.60% Maximum: 65.40%
Light-dark-rhythm : 12 hour light and 12 hour dark
Air Changes : More than 12 changes per hour

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
0, 2000 mg/kg bw
No. of animals per sex per dose:
Six Females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no
- Other examinations performed:
Clinical Observation
After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all surviving animals were observed once a day during the 14 day observation period.
Mortality
All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
Body weight
All surviving rats were weighed on days 0 (prior to dosing)
Pathology
At the end of 14 day observation period, all the survived rats were euthanised by overdose of CO2. All the animals were observed for external and internal gross pathology

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period
Clinical signs:
At 2000 mg/kg, all the animals were normal throughout the experimental period
Body weight:
Mean Body weight of all surviving animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0
Gross pathology:
No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice

Any other information on results incl. tables

 TABLES

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Body Weight (gram)

Body Weight Change (%)

Dose Volume*

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

1

G1/ 2000

1.5

149

172

183

15.44

22.82

2

1.6

160

191

197

19.38

23.13

3

1.6

158

186

198

17.72

25.32

4

1.6

160

179

188

11.88

17.50

5

1.6

160

195

196

21.88

22.50

6

1.6

161

192

205

19.25

27.33

*= Dose volume calculated based on day 0 body weight.

 

 


Table 2: Summary of Animal Body Weight (g) and Body Weight Changes (%)

 

Sex:Female

Group/ Dose (mg/kg)

Rats Body Weight (g)

Body Weight Changes (%)

Day 0

Day 7

Day 14

0-7

0-14

G1/ 2000

Mean

158.00

185.83

194.50

17.59

23.10

SD

4.52

8.80

7.82

3.51

3.30

n

6

6

6

6

6

Keys:SD = Standard Deviation, n = Number of Animals


Table 3: Individual Animal Clinical Signs and Symptoms

 

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Hours (Day 0)

1/2

1

2

3

4

1

G1/ 2000

1

1

1

1

1

2

1

1

1

1

1

3

1

1

1

1

1

4

1

1

1

1

1

5

1

1

1

1

1

6

1

1

1

1

1

 

Animal No.

Group/ Dose (mg/kg)

Days post dosing

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

G1/ 2000

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

1

1

1

1

1

1

1

6

1

1

1

1

1

1

1

1

1

1

1

1

1

1

Table 4: Individual Animal Mortality Record

 

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Day of Observation (Day 0 to 14)

Morning Observations

Evening Observations

1

G1/ 2000

No mortality and morbidity

No mortality and morbidity

2

No mortality and morbidity

No mortality and morbidity

3

No mortality and morbidity

No mortality and morbidity

4

No mortality and morbidity

No mortality and morbidity

5

No mortality and morbidity

No mortality and morbidity

6

No mortality and morbidity

No mortality and morbidity


Table 5: Gross Necropsy Observation

 

Sex:Female                                                                                                                                        

Animal No.

Group/ Dose (mg/kg)

Mode of Death

Gross Observation

External

Internal

1

G1/ 2000

TS

No abnormality detected

No abnormality detected

2

TS

No abnormality detected

No abnormality detected

3

TS

No abnormality detected

No abnormality detected

4

TS

No abnormality detected

No abnormality detected

5

TS

No abnormality detected

No abnormality detected

6

TS

No abnormality detected

No abnormality detected

Keys:TS= Terminal Sacrifice


Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 (Cut-off value) of “Hexasodium 2,2’-[vinylenebis[(3-sulphonato-4,1-phenylene)imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis(benzene-1,4-disulphonate) (CAS No. – 41098-56-0)” was >2000 mg/kg body weight.
Executive summary:

Acute Oral Toxicity Study of“Hexasodium 2,2’-[vinylenebis[(3-sulphonato-4,1-phenylene) imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis (benzene-1,4-disulphonate) (CAS No. – 41098-56-0)”in Rats, This study was performed as per OECD No. 423.

Six female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, food was withheld but drinking water providedad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body weight and no mortality was observed. Hence, further dosing was stopped. Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Mean body weight of all the animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0. At 2000 mg/kg, all the animals were normal throughout theexperimental period. No external and internal gross pathological changes were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. Under the conditions of this; acute oral toxicity study of“Hexasodium 2,2’-[vinylenebis[(3-sulphonato-4,1-phenylene) imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis (benzene-1,4-disulphonate) (CAS No. – 41098-56-0)”in female rats is as given below: The acute oral LD50(cut-off value) of“Hexasodium 2,2’-[vinylenebis[(3-sulphonato-4,1-phenylene) imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis (benzene-1,4-disulphonate) (CAS No. – 41098-56-0)”was >2000 mg/kgbody weight.Thus cosidering the CLP criteria of classification Hexasodium 2,2’-[vinylenebis[(3-sulphonato-4,1-phenylene)imino[6-(diethylamino)-1,3,5-triazine-4,2-diyl]imino]]bis(benzene-1,4-disulphonate) was found to be not classified .