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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 22 August 2007 and 05 September 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
Reaction mass of N,N’-bis-(3-methoxypropyl)-C22(branched)-alkyldiamide and N,N’-bis-(3-methoxypropyl)-C17(branched)-alkyldiamide
EC Number:
940-953-8
Molecular formula:
not applicable UVCB
IUPAC Name:
Reaction mass of N,N’-bis-(3-methoxypropyl)-C22(branched)-alkyldiamide and N,N’-bis-(3-methoxypropyl)-C17(branched)-alkyldiamide
Test material form:
other: off white waxy solid block

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Male New Zealand White rabbits were supplied by Harlan UK Limited.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (Certified Rabbit Diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 17 to 23°C.
- Humidity (%): Set to achieve limits of 30 to 70%.
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
A quantity of 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.
Duration of treatment / exposure:
4 hours
Observation period:
7 days.
Number of animals:
3
Details on study design:
TRANSCUTANEOUS ELECTRICAL RESISTANCE ASSAY:
In the absence of data suggesting that the test material was unlikely to produce severe irritation/corrosion, an ex vivo pre-screen test, the Transcutaneous Electrical Resistance (TER) Assay, was performed. The results of the pre-screen test indicated that the test material was considered not to be corrosive to the skin and the in vivo test was performed.

MEASUREMENT OF pH:
The pH of the test material was determined prior to commencement of the study and found to be as follows:
10% w/w aqueous preparation of the test material: pH 6.9 immediately, pH 7.0 after 10 minutes.

PROCEDURE:
On the day before the test each of a group of three rabbits was 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 material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. 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 material removed by gentle swabbing with cotton wool soaked in distilled water.

SCORING SYSTEM:
Approximately one hour following the removal of the patches, and 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

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

Any other skin reactions, if present, were also recorded.

An additional observation was made on Day 7 to assess the reversibility of skin reactions.









Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(66523 Male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(66524 Male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(66525 Male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(66523 Male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: No signs of oedema at any time point
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(66524 Male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(66525 Male)
Time point:
other: Mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: No signs of oedema at any time point
Irritant / corrosive response data:
Very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal and at the 24-hour observation with very slight erythema noted at one treated skin site at the 48 and 72-hour observation.

Very slight oedema was noted at one treated skin site one hour after patch removal and at the 24-hour observation.

Light brown discolouration of the epidermis was noted at one treated skin site at the 48 and 72-hour observations.

Two treated skin sites appeared normal at the 48-hour observation and the remaining treated skin site appeared normal at the 7-day observation.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced a primary irritation index of 1.0 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. According to the REGULATION (EC) No 1272/2008 (CLP) the test item is not classified for skin irritation.
Executive summary:

Introduction.

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 24 April 2002)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC

Initial considerations.

In the absence of data suggesting that the test material was unlikely to produce severe irritation/corrosion, an ex vivo pre-screen test, the Transcutaneous Electrical Resistance (TER) Assay, was performed. The results of the pre-screen test indicated that the test material was considered not to be corrosive to the skin and the in vivo test was performed.

Results.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight oedema. Light brown discolouration of the epidermis was also noted. Two treated skin sites appeared normal at the 48-hour observation and the remaining treated skin site appeared normal at the 7-day observation.

Conclusion.

The test material produced a primary irritation index of 1 .0 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. According to the REGULATION (EC) No 1272/2008 (CLP) the test item is not classified for skin irritation.