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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:
31 January to 14 February 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP study conducted in compliance with OECD Guideline No. 404 without any deviation. The substance is adequately identified, but some data on composition is missing. Therefore validation applies with restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
24 April 2002.
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Remarks:
Inspected on 2010-12-07 / Signed on 2011-03-07.

Test material

Constituent 1
Chemical structure
Reference substance name:
2,6-dimethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)cyclohex-2-en-1-ol
Cas Number:
1401065-88-0
Molecular formula:
C16 H26 O
IUPAC Name:
2,6-dimethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)cyclohex-2-en-1-ol
Test material form:
other: See specific details on each Endpoint Study Records
Details on test material:
- Storage condition of test material: Room temperature
Specific details on test material used for the study:
- Physical state: Colourless gel
- Date received: 13 January 2012

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste – F40260 Linxe).
- Weight at study initiation: 2.74 - 3.06 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SDS - C15), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: between ten and fifteen changes per hour.
- Photoperiod: 12 hours light/12 hours dark.

IN-LIFE DATES: From 31 January to 14 February.

Test system

Type of coverage:
semiocclusive
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
- Concentration (if solution): Test item was applied, as supplied.
Duration of treatment / exposure:
4 hours
Observation period:
Skin reactions were appreciated 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14 (in case of persistent reactions were observed).
Number of animals:
3 females
Details on study design:
PRETEST
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

TEST SITE
- Area of exposure: Undamaged skin area of the right flank of each animal
- Type of wrap if used: Patch was secured in position with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: After removal of the patch, the treated area was rinsed with distilled water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14 (in case of persistent reactions were observed).

SCORING SYSTEM:
- Method of calculation: Skin irritant reaction was scored as per Draize scale according to OECD guideline 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 2 days.
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 2 days.
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
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
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
- A very slight to well defined erythema was noted on the treated area of all animals, 1 hour after the patch removal.
- A very slight to moderate oedema was noted on the treated area of all animals, 1 or 24 hours after the patch removal.
- The erythematous reactions were totally reversible between days 1 and 7.
- The oedematous reactions were totally reversible between days 2 and 7. Dryness was noted from day 2 or day 3 in the three animals and was totally reversible on day 7.
Other effects:
None

Any other information on results incl. tables

Table 7.3.1/1: Individual and mean skin reactions/Erythema - Eschar formation following 4 hour exposure

Skin reaction

Observation time (following patch removal)

Individual Scores – Rabbit Number and Sex

A1812/Female

A1817/Female

A1818/Female

Erythema/Eschar formation

1 h

2

1

1

24 h

2

1

0

48 h

2

0

0

72 h

2

0

0

Day 7

0

0

0

Total (24, 48 and 72 hours)

6

1

0

Mean (24, 48 and 72 hours)

2

0.3

0

Table 7.3.1/2: Individual and mean skin reactions/Oedema formation following 4 hour exposure

Skin reaction

Observation time (following patch removal)

Individual Scores – Rabbit Number and Sex

A1812/Female

A1817/Female

A2166/Female

Oedema formation

1 h

3

1

0

24 h

3

2

2

48 h

2

0

0

72 h

1

0

0

Day 7

0

0

0

Total (24, 48 and 72 hours)

6

2

0

Mean (24, 48 and 72 hours)

2

0.7

0.7

Note:

A1812: dryness from D2 to D3

A1817: dryness at D3

A1818: dryness at D3.

Applicant's summary and conclusion

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

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test item was applied on an undamaged skin area of the flank of 3 female New Zealand White rabbits. On the other flank an untreated area was served as the control. Test sites were covered with a semi-occlusive dressing for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

A very slight to well defined erythema was noted on the treated area of all animals, 1 hour after the patch removal. A very slight to moderate oedema was noted on the treated area of all animals, 1 or 24 hours after the patch removal. The erythematous reactions were totally reversible between days 1 and 7. The oedematous reactions were totally reversible between days 2 and 7. Dryness was noted from day 2 or day 3 in the three animals and was totally reversible on day 7.

 

 

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 2 / 0.3/ 0.0 for erythema and 2.0 / 0.7 / 0.7 for oedema. These effects are reversible between days 2 and 7.

 

Therefore the test material is not classified as irritant to skin according to the annex I of the Regulation (EC) No. 1272/2008 and to the GHS.

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