Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

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
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 the test chemical after dermal application on the intact skin in Rabbits.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Castor oil, ethoxylated
EC Number:
500-151-7
EC Name:
Castor oil, ethoxylated
Cas Number:
61791-12-6
Molecular formula:
C57H104O9(CH2CH2O)n
IUPAC Name:
Castor oil, ethoxylated
Test material form:
liquid
Details on test material:
- IUPAC Name: Castor Oil, ethoxylated
- Smiles: CCCCCCC(CC=CCCCCCCCC(=O)OCC(C(=O)OCCCCCCCC=CCC(O)CCCCCC)OC(=O)CCCCCCC=CCC(O)CCCCCC)OCCOCCOCCOCCOCCO
- Molecular formula:C65H120O14
- Substance type:Organic
- Physical state:Liquid
Specific details on test material used for the study:
- IUPAC Name: Castor Oil, ethoxylated
- Smiles: CCCCCCC(CC=CCCCCCCCC(=O)OCC(C(=O)OCCCCCCCC=CCC(O)CCCCCC)OC(=O)CCCCCCC=CCC(O)CCCCCC)OCCOCCOCCOCCOCCO
- Molecular formula: C65H120O14
- Substance type: Organic
- Physical state: Liquid
- Batch number: Lot 1/12
- AI Content: 99.12 %
- Manufactured date: November, 2013
- Expiry Date: November, 2014
Handling and Disposal
- Safety precautions: Aprons, caps, mask, 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 or test system and environmental conditions:
TEST ANIMALS
- Sex: Male
- Source:Procured from RABBI ROOF, Hyderabad
- Age at study initiation:3.5 to 4.5 Months (Approximately)
- Weight (Prior to Treatment):Minimum: 1.612 kg and Maximum: 2.058 kg (Prior to Treatment)
- Health Status: Healthy young adults rabbits were used for the study.
- 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 (Nutrivet Life Sciences, Pune) 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 5 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: 20.00 °C and Maximum: 22.50 °C
- Humidity (%):Minimum: 47.00 % and Maximum: 68.40 %
- Air changes (per hr):More than 12 changes per hour.
- Photoperiod (hrs dark / hrs light):12:12

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 ml

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

REMOVAL OF TEST SUBSTANCE
- Washing (if done):The residual test item was removed by using cotton soaked in distilled water.
- Time after start of exposure:4 hour

SCORING SYSTEM:Draize Method

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The following were observed in treated rabbits.
The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per Draize method.

In Animals No.1 and 3 after post patch removal, revealed no erythema and oedema at 24 and 48 and 72 hour during the observation period.

After 4 hours of exposure in Animal No. 2, there was 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 2.

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.

Any other information on results incl. tables

Table 1: Skin Reaction

 

In Treated area Dose:0.5 ml of test item                                                               Sex:Male

 

Animal

No.

Test

Treated

 area*

Erythema score

Oedema score

1h

24h

48h

72h

1h

24h

48h

72h

1

Initial

Left

0

0

0

0

0

0

0

0

2

Confirmatory

Left

1

0

0

0

0

0

0

0

3

Left

0

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

Right

0

0

0

0

0

0

0

0

3

Right

0

0

0

0

0

0

0

0

Key: h = Hour.

Erythema                                                                                                       Oedema

0 =No erythema                                                                                           0 =No oedema


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 Body Weight

Sex:Male

Animal

No.

Body Weight (kg)

Prior to Dosing

At termination

1

2.058

2.098

2

1.784

1.788

3

1.612

1.640


Table 3: Individual AnimalClinicalSigns

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 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 the test chemical was Non-Irritating to the skin of Male New Zealand White rabbits under the experimental conditions tested and being classified as “Not Classified” as per GHS Classification.
Executive summary:

Acute Dermal Irritation/corrosion Study of the test chemical in Rabbits, was performed as per OECD guideline No. 404. Three healthy young adult male New Zealand White rabbits were used for conducting acute dermal irritation/corrosion study. Body weights were recorded on day 0 (prior to application) and at termination. Rabbits with good intact skin were selected for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of 0.5 ml of test item (as such) 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 and 0.5 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, there was No erythema and oedema observed at 1, 24 and 48 hours observation.Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3)to confirm the non irritant nature of the test item.After 4 hours of exposure in Animal No. 2, there was 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 2. In Animals No. 3 at 1, 24, 48 and 72 hour observation after post patch removal, revealed no erythema and oedema during the observation period. The patch was removed after 4 hours and rabbits wereobservedfor erythema and oedemaat 1, 24, 48 and 72 hours after patch removal, evaluatedand graded as per Draize method.

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 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 the test chemical was Non-Irritating to the skin of Male New Zealand White rabbits under the experimental conditions tested and  being classified as “Not Classified” as per GHS Classification.