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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from study report

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:
Acute dermal toxicity test was carried out to study the effects of test chemical on rats.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (IUPAC name): Sodium salicylate
- Common name: Monosodium salicylate
- Molecular formula: C7H6O3.Na
- Molecular weight: 160.1035 g/mol
- Smiles notation: c1(c(cccc1)O)C(=O)[O-].[Na+]
- InChl: 1S/C7H6O3.Na/c8-6-4-2-1-3-5(6)7(9)10;/h1-4,8H,(H,9,10);/q;+1/p-1
- Substance type: Organic

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: In-House Bred
- Age at study initiation: Healthy young adult were used.Females were nulliparous and non pregnant.
- Weight at study initiation: Male: Minimum: 218 g and Maximum: 261 g
(Prior to Treatment) Female:Minimum: 210 g and Maximum: 221 g

- Fasting period before study: no data
- Housing:
Bedding : All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) Batch No.: SPAR – 25/2014
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.
- Diet (e.g. ad libitum): animals were provided conventional laboratory rodent diet ad libitum
- Water : Aqua guard filtered tap water was provided ad libitum via drinking bottles.
- Acclimation period: All animals were acclimatized to the test conditions for 6 days prior to administration of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 19.90 °C Maximum: 23.30 °C
- Humidity (%): Minimum: 52.30% Maximum: 66.50%
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: Approx. 10% of body surface area of rat
- Type of wrap if used: porous gauze dressing and non-irritating tape

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): Individual rat was applied with an amount of test item moistened with 0.2 ml distilled water
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.2 ml
Duration of exposure:
24 hrs
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
total:10 animals
2000 mg/kg bw:male 5 and female:5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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 for clinical signs, teice daily for mortality
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
no data available

Results and discussion

Preliminary study:
no data available
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
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:
All the animals were observed with normal clinical signs throughout the experimental period
Body weight:
In males and females, mean body weight was observed with gain on day 7 and 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
Other findings:
no data available

Any other information on results incl. tables

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

222

232

248

4.50

11.71

2

237

243

256

2.53

8.02

3

261

279

314

6.90

20.31

4

255

276

297

8.24

16.47

5

218

229

232

5.05

6.42

6

Female

214

231

244

7.94

14.02

7

212

222

228

4.72

7.55

8

221

237

253

7.24

14.48

9

210

222

241

5.71

14.76

10

213

220

232

3.29

8.92

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

Key: 1 = Normal

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

Summaryof Animal Body Weight (g) and Body Weight Changes (%)

Dose:2000 mg/kg body weight

Sex

Body Weight (gram)

Body Weight Changes (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

Male

Mean

238.60

251.80

269.40

5.44

12.59

SD

19.19

24.06

34.59

2.20

5.80

n

5

5

5

5

5

Female

Mean

214.00

226.40

239.60

5.78

11.95

SD

4.18

7.30

9.91

1.88

3.43

n

5

5

5

5

5

Keys:SD= Standard deviation, n = Number of animals

GrossNecropsyObservation

 Dose:2000 mg/kg body weight                                               Mode of Death:Terminal Sacrifice

Animal No.

Sex

Gross Observation

External

Internal

1

Male

No abnormality detected

No abnormality detected

2

No abnormality detected

No abnormality detected

3

No abnormality detected

No abnormality detected

4

No abnormality detected

No abnormality detected

5

No abnormality detected

No abnormality detected

6

Female

No abnormality detected

No abnormality detected

7

No abnormality detected

No abnormality detected

8

No abnormality detected

No abnormality detected

9

No abnormality detected

No abnormality detected

10

No abnormality detected

No abnormality detected

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Conclusions:
The LD50 value was considered to be >2000 mg/kg bw,when male and female wistar rats were occlusively treated with test chemical by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).
Executive summary:

Acute dermal Toxicity Study of test chemical in Rats was performed as per OECD No. 402 (Acute Dermal Toxicity) . Five male and five female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free 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 directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area.This porous gauze dressing was covered with a non-irritating tape.After the 24-hour application period, the dressings were removed and theskin was gently wiped with distilled water.The skin reactions were assessed. All animals were observed for clinical signs at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1‑14. Mortality was recorded after application on test day 0 and twice daily during days 1-14 (at least once on the day of sacrifice). Local signs / Skin reactions were observed daily from test days 1-14 (in common with clinical signs). Body weights were re­corded on day 0 (prior to application) and on day 7 and 14. All animals were necropsied and examined macroscopically. No mortality was observed in any animal till the end of the experimental period. All the animals shows normal clinical signs, mean body weight was observed with gain on day 7 and 14. Gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.Thus, The LD50 value was considered to be >2000 mg/kg bw,when male and female  wistar rats were occlusively treated with test chemical (54-21-7)  by dermal application following 14 days of observation period according to OECD Guideline 402 (Acute Dermal Toxicity).