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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
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 reports

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
The objective of the study was to assess the irritant and/or corrosive effects of test chemical after topical application on the intact skin in rabbits.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Sodium salicylate
- Molecular Formula: C7H6O3.Na
- Molecular Weight: 160.105 g/mol
- Smiles Notation: c1(c(cccc1)O)C(=O)[O-].[Na+]
- InChI: 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
- Physical State: Solid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Sodium salicylate
- Name of test material (as cited in study report): Sodium salicylate
- Molecular Formula: C7H6O3.Na
- Molecular Weight: 160.105 g/mol
- Smiles Notation: c1(c(cccc1)O)C(=O)[O-].[Na+]
- InChI: 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
- Physical State: Solid
- AI Content (assay): 99.8%
- Manufactured data: March, 2013
- Expiry Date : February, 2015
- Storage conditions: Room temperature (20 - 30 °C)
Handling and Disposal
Safety precautions : Aprons, masks, caps, gloves and goggles were used to ensure the health and safety of the personnel.
Disposal : The remaining unused test item was disposed as per internal SOPs

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Sex: Male
- Source: LIVEON BIOLABS PVT LTD
- Age at study initiation: 3 to 4 Months (Approximately)
- Weight at study initiation: Minimum: Minimum: 1.764 kg & Maximum: 2.384 kg (Prior to Treatment)
- Housing: The animals were housed individually in stainless steel 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 minimum twice a week.
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rabbit diet ad libitum
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum
- Acclimation period: Rabbits were acclimatised to the test conditions for a period of 6 days (Animal No.-1) and 8 days (Animal No.-2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 20.30 °C Maximum: 22.70 °C
- Humidity (%):Minimum: 48.30 % Maximum: 68.30 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light):12:12 hours

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with 0.5 ml distilled water


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution):no data
- Lot/batch no. (if required): no data
- Purity: no data
Duration of treatment / exposure:
4-hour exposure period
Observation period:
72 hours
Number of animals:
Three male rabbits
Details on study design:
TEST SITE
- Area of exposure: dorsal lumbar region at contralateral sites
- % coverage: approximately 6 X 6 cm
- Type of wrap if used: porous gauze dressing and non-irritating tape (Micropore 3”)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was removed by using cotton soaked in distilled water
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Grading of irritation lesions was carried out as per Draize Method

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Animal 1,2,3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
Animal 1,2 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Animal No. 1, showed very slight erythema (barely perceptible) and no oedema at 1 hour of observation. At 24, 48 and 72 hour observation no erythema and oedema was observed in animal No 1.
In Animals No. 2 and 3 at 1 hour observation post patch removal, revealed very Slight erythema (barely perceptible) and no oedema. At 24, 48 and 72 hour post patch removal, animals showed no erythema and no oedema..
The individual mean score at 24, 48 and 72 hours for Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively

Other effects:
Clinical Observation
No systemic toxicity was observed at treated rabbits during the experimental period.


Mortality
No mortality was observed during the observation period


Body Weights
Body weights were increased as compared to day 0 in all the three animals



Any other information on results incl. tables

Table 1: Skin Reaction

 

In Treated area 

Dose:500 mg of test item (moistened with 0.5 ml distilled water)            

Sex:Male 

Animal

No.

Test

Treated

 area*

Erythema score

Oedema score

1h

24h

48h

72h

1h

24h

48h

72h

1

Initial

Left

1

0

0

0

0

0

0

0

2

Confirmatory

Right

1

0

0

0

0

0

0

0

3

Right

1

0

0

0

0

0

0

0

 

In Control area

Dose:0.5 ml of distilled water                                                              

Sex:Male 

Animal

No.

Test

Treated area*

Erythema score

Oedema score

1h

24h

48h

72h

1h

24h

48h

72h

1

Initial

Right

0

0

0

0

0

0

0

0

2

Confirmatory

Left

0

0

0

0

0

0

0

0

3

Left

0

0

0

0

0

0

0

0

Key: h = Hour.

Erythema                                                                                                       Oedema

0 =No erythema                                                                                           0 =No oedema

1 = Very slight erythema(barely perceptible)

Mean Individual Animal Score at 24, 48 and 72 hours

 

                     Animal Number                  

Observations                      

1

2

3

Erythema

0.00

0.00

0.00

Oedema

0.00

0.00

0.00

 

Table 2: Individual Animal BodyWeight

Sex:Male

Animal

No.

Body Weight (kg)

Prior to Dosing

At termination

1

2.314

2.360

2

2.384

2.420

3

1.764

1.836

Individual Animal Clinical Signs

Sex:Male

Animal

No.

Days (Post dosing Observation)

0

1

2

3

1

1

1

1

1

2

1

1

1

1

3

1

1

1

1

Key: ./. = Not Applicable. 1 = Normal.

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Conclusions:
No erythema and oedema (skin irritation) were found at the end of 72 hour observation period after patch removal.The individual mean score at 24, 48 and 72 hoursfor Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively
Hence, it was concluded that Sodium salicylate was Non-Irritating to the skin of Male New Zealand White rabbits under the experimental conditions tested
Executive summary:

Acute Dermal Irritation/corrosion Study of Sodium Salicylate (CAS: 54 -21 -7) in Rabbits, was performed in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access,2014) as per OECD guideline No. 404. Three healthy young adult male rabbits were used for conducting acute dermal irritation/corrosion study.

The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of 0.5 g of test item (moistened with 0.5 ml distilled water) was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits. The other untreated side was kept as control area and0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water without altering the integrity of the epidermis. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in animal no. 1, very slight erythema (barely perceptible) and no oedema observed at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and oedema was observed in animal no 1. No severe skin lesions were observed hence a confirmatory test was conducted on additional two rabbits (No. 2 and 3) after 24 hours to confirm the non irritant nature of the test item. The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours post patch removal, evaluated and graded as per Draize method. In animal no. 2 and 3 at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema. At 24, 48 and 72 hour post patch removal, animals showed no erythema and no oedema. The individual mean score at 24, 48 and 72 hours for Animal Nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively

Hence, it was concluded that Sodium salicylate was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested and classified as "Not Classified" as per CLP criteria.