Esterification products of dihydrofuran-2,5-dione, C16-24 (even numbered) alkenyl with propane-1,2,3-triol and propane-1,2,3-triol oligomers

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 April 2014 to 15 April 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study followed the OECD 404 Guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Method B4 Acute Toxicity (Skin Irriation) of Commission Directive 2004/73/EC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Esterification products of dihydrofuran-2,5-dione, C16-24 (even numbered) alkenyl with propane-1,2,3-triol and propane-1,2,3-triol oligomers

EC Number:

940-875-4

Molecular formula:

C3H8O3 - C99H182O20

IUPAC Name:

Esterification products of dihydrofuran-2,5-dione, C16-24 (even numbered) alkenyl with propane-1,2,3-triol and propane-1,2,3-triol oligomers

Test material form:

other: viscous amber liquid

Details on test material:

Description: amber coloured extremely viscous liquid
Storage: room temp in dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Leicestershire, UK
- Housing: Individual, suspended cages


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
The dosage level was 0.5 ml/site and an adjacent area of untreated skin served as the control site.

Duration of treatment / exposure:

On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.

Observation period:

Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation.

Number of animals:

2 rabbits (The number of animals used was the minimum required to achieve the objectives of the study. Testing was conducted in two animals and the response in those animals was such that exposure of a third animal would not affect classification of the test item, no further testing was needed.)

Details on study design:

On the day before the test two rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study. On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water. Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:
EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar formation preventing grading of erythema 4
Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and extending beyond the area of exposure) 4
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
An additional observation was made on Day 7 to assess the reversibility of skin reactions.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1.833

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

See results tables attached for individual animal scores.
Very slight erythema and very slight edema were noted at both treated skin sites one hour after patch removal with well-defined erythema and very slight or slight edema noted at the 24 and 48-Hour observations. Well-defined erythema and slight edema were noted at one treated skin site with very slight erythema and very slight edema noted at the other treated skin site at the 72-Hour observation. Loss of skin elasticity was also noted at both treated skin sites at the 72-Hour observation.
The dermal reactions were completely reversible, starting on Day 3, and both treated skin sites appeared normal at the 7-Day observation.

Other effects:

Loss of skin elasticity at 72 hours in both animals. Effect reversed within 7-day observation period.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance is not a skin irritant in rabbits.
In accordance with EU CLP Regulation (EC) No. 1272/2008 classification of this substance is not required for dermal irritation because scores for erythema and edema did not fulfill the criteria for classification. In addition the primary effects, erythema and edema, were fully reversible by the end of the 7-day observation period.

Executive summary:

Test Guidance

OECD Guideline No. 404 and EU Method B4

Introduction

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit.

Method and materials

On the day before the test two rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study. On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water. Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the Draize scheme.

Results

A single 4-Hour, semi-occluded application of the test item to the intact skin of two rabbits produced well-defined erythema, very slight or slight edema and loss of skin elasticity. The dermal reactions were completely reversible, starting on Day 3, and both treated skin sites appeared normal at the 7-Day observation.

Conclusion

The test item produced a primary irritation index of 3.3. No corrosive effects were noted.

In accordance with EU CLP Regulation (EC) No. 1272/2008 classification of this substance is not required for dermal irritation because scores for erythema and edema did not fulfill the criteria for classification. In addition the primary effects, erythema and edema, were fully reversible by the end of the 7-day observation period.