2,6-dimethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)cyclohex-2-en-1-ol

Skin irritation / corrosion

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 April 2002.

Deviations:

no

Test guideline 2

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

Test material information

Constituent 1

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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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.