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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
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:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The objective of the study was to assess the dermal toxicity of Solvent blue 4 (CAS No. – 6786-83-0) after single dose application by dermal route in rats and an observation period of 14 days.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):Solvent blue 4
- Molecular formula :C33H33N3O
- Substance type:Organic
- Physical state:BLACKISH POWDER
- Lot/batch No.:Lot 1/02
- Analytical purity:99.02%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:In-House Bred at Sa-Ford, Animal Facility.
- Age at study initiation:N/A
- Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
- Weight (Prior to Treatment)::Male:Minimum: 242 g and Maximum: 262 g (Prior to Treatment)Female:Minimum: 221 g and Maximum: 249 g
- Fasting period before study:N/A
- Housing:The animals were housed individually in polycarbonate cages.
- Bedding : All cages were provided with corn cobs.
- 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.
- Diet (e.g. ad libitum):All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum.
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period:All animals were acclimatized to the test conditions for 5 days prior to administration of the test item.
- Randomization : Animals were selected manually. No computer generated randomization program was used

ENVIRONMENTAL CONDITIONS
-Temperature :Minimum: 19.80 °C Maximum: 23.20 °C
-Relative humidity:Minimum: 50.60% Maximum: 61.10%
-Light-dark-rhythm:12:12
-Air Changes :More than 12 changes per hour


Administration / exposure

Type of coverage:
other: porous gauze dressing covered with a non-irritating tape
Vehicle:
other: distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure:The test item was applied uniformly over clipped dorsal area of rat skin.
- % coverage:Approximately 10% body surface area of rat.
- Type of wrap if used:The porous gauze dressing and non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):The residual test item was removed by using distilled water.
- Time after start of exposure:24-hour.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):A limit dose of 2000 mg/ kg body weight of test item was applied.
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit):0.2 ml distilled water
- Concentration (if solution):N/A
- Lot/batch no. (if required):N/A
- Purity:N/A
Duration of exposure:
24 hrs
Doses:
2000 mg/kg body weight.
No. of animals per sex per dose:
10 (Five per sex)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Daily
- Necropsy of survivors performed: yes
At the end of 14 day observation period, all the surviving rats were euthanised by overdose of CO2 and subjected to gross pathology examination, for external and internal observations.
- Other examinations performed:
- Clinical signs : After test item administration, individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period.

-Mortality
Animals were observed twice daily for any mortality during the experimental period

- Body weight: All rats were weighed on days 0 (prior to dosing), 7 and 14..

other:
-Pathology
At the end of 14 day observation period, all the surviving rats were euthanised by overdose of CO2 and subjected to gross pathology examination, for external and internal observations.
Statistics:
No statistical analysis was performed since the study was terminated with limit test.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Non toxic to animals
Mortality:
No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period.
Clinical signs:
No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period
Body weight:
In males, mean body weight was observed with increase on day 7 and 14, as compared to day 0. In females, mean body weight was observed with decrease on day 7 and increase on day 14, as compared to day 0
Gross pathology:
The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality

Any other information on results incl. tables

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

 

Dose: 2000 mg/ kg bodyweight      

Animal No.

Sex

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

1

Male

262

260

289

-0.76

10.31

2

242

258

281

6.61

16.12

3

251

269

300

7.17

19.52

4

260

271

302

4.23

16.15

5

258

274

310

6.20

20.16

6

Female

228

231

240

1.32

5.26

7

221

219

225

-0.90

1.81

8

249

241

246

-3.21

-1.20

9

224

216

218

-3.57

-2.68

10

230

231

240

0.43

4.35

                                                                                                   

Table 2: Individual Animal Clinical Signs and Symptoms

 

Dose: 2000 mg/kg body weight

Animal

No.

Sex

Hour(s) - Day 0

Day

1

2

3

4

1

2

3

4

5

6

7

1

Male

1

1

1

1

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

1

1

1

1

6

Female

1

1

1

1

1

1

1

1

1

1

1

7

1

1

1

1

1

1

1

1

1

1

1

8

1

1

1

1

1

1

1

1

1

1

1

9

1

1

1

1

1

1

1

1

1

1

1

10

1

1

1

1

1

1

1

1

1

1

1

Animal

No.

Sex

Day

8

9

10

11

12

13

14

1

Male

1

1

1

1

1

1

1

2

1

1

1

1

1

1

1

3

1

1

1

1

1

1

1

4

1

1

1

1

1

1

1

5

1

1

1

1

1

1

1

6

Female

1

1

1

1

1

1

1

7

1

1

1

1

1

1

1

8

1

1

1

1

1

1

1

9

1

1

1

1

1

1

1

10

1

1

1

1

1

1

1

Keys: 1 = Normal

Table 3: Individual Animal Mortality Record

 

Dose: 2000 mg/kg body weight

       Animal No.

Sex

Days of Observation (0 to 14)

Morning Observations

Evening Observations

1

Male

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

Female

No mortality and morbidity

No mortality and morbidity

7

No mortality and morbidity

No mortality and morbidity

8

No mortality and morbidity

No mortality and morbidity

9

No mortality and morbidity

No mortality and morbidity

10

No mortality and morbidity

No mortality and morbidity


Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose of Solvent blue 4 (CAS No. – 6786-83-0) was >2000 mg/kg body weight.Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that Solvent blue 4 (CAS No. – 6786-83-0) does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.



Executive summary:

Acute Dermal Toxicity Study of “ Solvent blue 4 (CAS No. – 6786-83-0)” was studied in Wistar Rats, This study was performed as per OECD No.402. Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Ratsfree from injury and irritation of skin were selected for the study. Twenty four hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, anamount oftestitem moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area.

All the animals were observed with normal clinical signs throughout the experimental period .No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period.

In males, mean body weight was observed with increase on day 7 and 14, as compared to day 0. In females, mean body weight was observed with decrease on day 7 and increase on day 14, as compared to day 0.The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality

Under the conditions of this; acute dermal toxicity study of Solvent blue 4 (CAS No. - 6786 -83 -0)in rats is as given below:

The acute dermal median lethal dose of Solvent blue 4 was >2000 mg/kg body weight.Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that Solvent blue 4 does not exhibit acute dermal toxicity i.e it is acutely non toxic to animals.