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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
Study period:
From June 14 to 17, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(5,5-dimethyl-1-cyclohexen-1-yl)pent-4-en-1-one
EC Number:
260-486-7
EC Name:
1-(5,5-dimethyl-1-cyclohexen-1-yl)pent-4-en-1-one
Cas Number:
56973-85-4
Molecular formula:
C13H20O
IUPAC Name:
1-(5,5-dimethylcyclohex-1-en-1-yl)pent-4-en-1-one
Constituent 2
Chemical structure
Reference substance name:
1-(3,3-dimethylcyclohex-1-en-1-yl)pent-4-en-1-one
Cas Number:
56973-84-3
Molecular formula:
C13H20O
IUPAC Name:
1-(3,3-dimethylcyclohex-1-en-1-yl)pent-4-en-1-one
Test material form:
liquid
Remarks:
Colorless to pale yellow liquid
Details on test material:
- Storage condition of test material: In a refrigerator (2-8°C)
- Stability under test conditions: Stable at storage conditions

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes, 01400 Chatillon sur Chalaronne, France
- Age at study initiation: 13 weeks
- Weight at study initiation: Animal n°1: 3034g ; Animal n°2: 2861g ; Animal n°3: 2447g
- Housing: Animals were housed individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 64/99) from Provimi Kliba AG, 4303 Kaiseraugst, Switzerland
- Water: Community tap water from Itingen, ad libitum, in water bowls.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 20±3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: June 08, 1999 To: June 17, 1999.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
the dorsal fur was clipped with an electric clipper approximately 3 days before treatment
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 h after patch removal.
Number of animals:
1 male and 2 females
Details on study design:
TEST SITE
- Area of exposure: Dorsal area of the trunk (left side only)
- Type of wrap if used: Test material was applied to approximately 6 cm² of the intact skin of the clipped area. It was covered with a 2.5 x 2.5 cm patch of surgical gauze and the gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions were clearly visible at that time.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS:
- viability: daily
- skin reaction: at approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test article.
- clinical signs: daily during the observation period
- body weight: at start of acclimatization, on the first day of application and at termination of observation

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
- Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 0.22.
- Local signs (mean values from 24 to 72 hours) consisted of grade 0.11 erythema and grade 0.11 oedema. In one animal, very slight erythema and very slight swelling were observed until 24 hours after treatment. All signs of irritation were reversible after 48 hours.
- No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
- No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occured.
- No staining by the test article of the treated skin was observed.
- The body weight of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

Table 7.3.1/1: Skin irritation scores - individual and mean values

Score at time point

Erythema (Animal no 1 / 2 / 3)

Max. score 4

Oedema (Animal no 1 / 2 / 3)

Max. score 4

1 h

1 / 0 / 0

1 / 0 / 0

24 h

1 / 0 / 0

1 / 0 / 0

48 h

0 / 0 / 0

0 / 0 / 0

72 h

0 / 0 / 0

0 / 0 / 0

Average 24, 48 and 72 h

0.33 / 0.0 / 0.0

0.33 / 0.0 / 0.0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, test material is not classified as irritant to the skin according to the criteria of the Annex VI of Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.
Executive summary:

In a dermal irritation study performed according to the EU Method B.4 and according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of the test material was applied on the clipped skin of three New Zealand White rabbits (1 male and 2 females). The test material was held in contact with the skin by means of a semi-occlusive dressing for 4 h. Skin reactions were assessed and scored according to the Draize scale at 1, 24, 48 and 72 h after removal of the dressing and test article.

Formation of erythema and oedema of score 1 in the male rabbit were observed 1 h and 24 h after patch removal. Observed oedematous and erythematous reactions had both completely disappeared within 48 h. No cutaneous reaction was observed in the female rabbits at any time.

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 0.33 / 0.0 / 0.0 for erythema and 0.33 / 0.0 / 0.0 for oedema.

Under the test conditions, test material is not classified as irritant to the skin according to the criteria of the Annex VI of Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.