(2-methyl-5-propan-2-ylcyclopentyl) propanoate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 18 May and 08 June 2010

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:

2010

Report date:

2010

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)

Version / remarks:

30 May 2008

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2009-09-03 / Signed on 2009-12-10

Test material

Test material information

Constituent 1

Reference substance name:

(2-methyl-5-propan-2-ylcyclopentyl) propanoate [ISOMER 1]

Molecular formula:

C12 H22 O2

IUPAC Name:

(2-methyl-5-propan-2-ylcyclopentyl) propanoate [ISOMER 1]

Constituent 2

Reference substance name:

(2-methyl-5-propan-2-ylcyclopentyl) propanoate [ISOMER 2]

Molecular formula:

C12 H22 O2

IUPAC Name:

(2-methyl-5-propan-2-ylcyclopentyl) propanoate [ISOMER 2]

Constituent 3

Reference substance name:

(2-methyl-5-propan-2-ylcyclopentyl) propanoate [ISOMER 3]

Molecular formula:

C12 H22 O2

IUPAC Name:

(2-methyl-5-propan-2-ylcyclopentyl) propanoate [ISOMER 3]

Constituent 4

Reference substance name:

(2-methyl-5-propan-2-ylcyclopentyl) propanoate [ISOMER 4]

Molecular formula:

C12 H22 O2

IUPAC Name:

(2-methyl-5-propan-2-ylcyclopentyl) propanoate [ISOMER 4]

Test material form:

liquid

Details on test material:

- Physical state: colourless translucent liquid
- Storage condition of test material: Room temperature

Specific details on test material used for the study:

Date received: 10 May 2010

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: 2.15 - 2.77 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 (from public system), ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: From 18 May to 08 June 2010.

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 one 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:

0.7

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

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 3

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 5 days

Remarks on result:

probability of mild irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

probability of mild 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: 3 days

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

- A well defined erythema, associated with a very slight to slight oedema, was noted on the treated area of all animals, 24 hours after the patch removal.
- The erythematous reaction was totally reversible between days 2 and 7 and the oedematous reaction was totally reversible between days 2 and 5.
- A slight dryness was noted from day 2, day 4 or day 5 and was totally reversible on day 13 in one animal and remained on day 14 (last day of the study) in the two others.

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
		A0222/Female	A0243/Female	A0244/Female
Erythema/Eschar formation	1 h	1	2	2
	24 h	2	2	2
	48 h	0	2	2
	72 h	0	1	1
	Day 4	-	1	0
	Day 5	-	1	0
	Day 6	0	1	0
	Day 7	0	0	0
	Total (24, 48 and 72 hours)	2	5	5
	Mean (24, 48 and 72 hours)	0.7	1.7	1.7

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
		A0222/Female	A0243/Female	A0244/Female
Oedema formation	1 h	1	2	2
	24 h	2	2	1
	48 h	0	2	1
	72 h	0	1	0
	Day 4	-	1	0
	Day 5	-	0	0
	Day 6	0	0	0
	Day 7	0	0	0
	Total (24, 48 and 72 hours)	2	5	2
	Mean (24, 48 and 72 hours)	0.7	1.7	0.7

Note:

A0222: slight dryness days 2 & 3, between day 6 and day 14

A0243: slight dryness day 5, day 6, between day 8 and day 10 day 13 & day 14; dryness day 7

A0244: slight dryness between day 4 and day 10

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Under the test conditions, test substance is not classified as irritating to skin according to the criteria of the Annex I of the Regulation EC No. 1272/2008 (CLP) and classified in Category 3 (mild irritant) according 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 well defined erythema, associated with a very slight to slight oedema, was noted on the treated area of all animals, 24 hours after the patch removal. The erythematous reaction was totally reversible between days 2 and 7 and the oedematous reaction was totally reversible between days 2 and 5. A slight dryness was noted from day 2, day 4 or day 5 and was totally reversible on day 13 in one animal and remained on day 14 in the two others.

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 0.7 / 1.7 / 1.7 for erythema and 0.7 / 1.7/ 0.7 for oedema.

Under the test conditions, test substance is not classified as irritating to skin according to the criteria of the Annex I of the Regulation EC No. 1272/2008 (CLP) and classified in Category 3 (mild irritant) according to the GHS.

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