Reaction product of D-Glucopyranoside, methyl; esterified with oleic acid, methyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-04-21 - 2015-04-24

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The department of health of the Government of the United Kingdom

Test material

Test material information

Constituent 1

Reference substance name:

Reaction product of D-Glucopyranoside, methyl; esterified with oleic acid, methyl ester

EC Number:

946-364-2

Molecular formula:

C43H78O8

IUPAC Name:

Reaction product of D-Glucopyranoside, methyl; esterified with oleic acid, methyl ester

Test material form:

liquid

Details on test material:

- State of aggregation: yellow liquid
-Others: storage at room temperature, in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Hsdlf:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.75 or 3.0 kg
- Housing: individually in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 hrs continuous light (06:00 to 18:00) and 12 hrs darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL / site

Duration of treatment / exposure:

4 hrs

Observation period:

approximately 1, 24, 48 and 72 hrs after removal of the patches

Number of animals:

Two males.
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:

TEST SITE
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.
- Area of exposure: 2.5 cm x 2.5 cm on backs
- Type of wrap if used: 2.5 cm x 2.5 cm cotton gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing: corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hrs

OBSERVATION TIME POINTS
approximately 1, 24, 48 and 72 hrs after removal of the patches

SCORING SYSTEM:
- Examination for evidence of primary irritation and scored according to the following scale:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar 4
formation preventing grading of erythema

Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by 2
definite raising)
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and 4
extending beyond the area of exposure)

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Method of calculation:
Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme
The scores for erythema and edema at the 24 and 72-hour readings were totaled for the two test rabbits (8 values) and this total was divided by 4 to give the primary irritation index of the test item. The test item was graded according to the following scheme devised by Draize, J.H. (1959):

Primary Irritation Index Grading of Irritancy
0 Non-irritant
> 0 to 2 Mild irritant
>2 to 5 Moderate irritant
> 5 to 8 Severe irritant

If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test item is considered to be corrosive to rabbit skin. Grading according to Draize may, therefore, not be applicable.

Results and discussion

In vivo

Results

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

Very slight erythema and very slight edema were noted at both treated skin sites 1 hour after patch removal.
The treated skin sites appeared normal at the 24-Hour observation.

Other effects:

Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 1: Individual Skin Reactions

Skin Reaction	Observation Time (following patch removal)	Individual Scores		Total
		Rabbit number and Sex
		75038 Male	75039 Male
Erythema/Eschar Formation	Immediately	0	0	0
	1 Hour	1	1	(2)
	24 Hours	0	0	0
	48 Hours	0	0	(0)
	72 Hours	0	0	0
Edema Formation	Immediately	0	0	0
	1 Hour	1	1	(2)
	24 Hours	0	0	0
	48 Hours	0	0	(0)
	72 Hours	0	0	0
Sum of 24 and 72-Hour Readings (S): 0	0
Pimary Irritation Index (S/4): 0/4 =	0.0
Grading:	NON-IRRITANT

( )= Total values not required for calculation of ptimary irritation index

Table 2: Individual Body Weights and Body Weight Change

Rabbit Number and Sex	Individual Body Weight (kg)		Body Weight Change (kg)
	Day 0	Day 3
75038 Male	3.00	3.02	0.02
75039 Male	2.75	2.80	0.05

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item produced a primary irritation index of 0.0 and was considered to be non-irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.

Executive summary:

The primary dermal irritation potential of the test item was evaluated in this study with New Zealand White rabbits (2M) in accordance with OECD Guideline 404 and GLP requirements. There was one group of two male albino rabbits that received a single, four-hour, semioccluded exposure. Each 0.5 mL dose of the test article was applied to the clipped, unabraded skin. At completion of exposure, the bandages were removed and the sites washed. Application sites were evaluated in accordance with the method of Draize at approximately 1 and 24, 48 and 72 hours after patch removal. There were no remarkable body weight changes during the study period. The test article induced very slight erythema and edema on all animals at 1 hrs after removal of the patch. The skin appeared normal again at 24 hrs. No corrosive effects were noted. The Primary Irritation Index was calculated to be 0.0. The test article received a descriptive rating classification of non-irritating.