3-ETHYL-5,5-DIMETHYL-GAMMA BUTYROLACTONE

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 24 June and 15 July 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 404.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

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:

Directive n° 2004/73/EC.

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2008-04-14&15 / Signed on 2008-07-16.

Test material

Test material information

Constituent 1

Reference substance name:

(3S)-3-ethyl-5,5-dimethyloxolan-2-one

Molecular formula:

C8 H14 O2

IUPAC Name:

(3S)-3-ethyl-5,5-dimethyloxolan-2-one

Constituent 2

Reference substance name:

(3R)-3-ethyl-5,5-dimethyloxolan-2-one

Molecular formula:

C8 H14 O2

IUPAC Name:

(3R)-3-ethyl-5,5-dimethyloxolan-2-one

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:

- The test item was considered at 100% for the study
- Date received: 02 June 2008

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: 2.17 - 3.07 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 distribution, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-24°C
- Humidity: 40-66%
- Air changes: at least ten changes per hour.
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From 24 June To 15 July 2008.

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.

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:

0.3

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

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of 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:

1

Max. score:

4

Reversibility:

fully reversible within: 3 days

Remarks on result:

probability of weak 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:

- It was noted, 24 hours after the test item application, on the treated area, a slight to well defined erythema associated with a slight oedema in two animals. The oedematous reactions were totally reversible at D2 and the erythematous reactions were totally reversible between D2 and D3.
- On the cutaneous structure, slight dryness was noted on the treated area, from D2 in two animals and from D3 in the last one. Slight dryness was still noted at the end of the observation time (D14) in two animals.

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
		A9134/Female	A9149/Female	A9150/Female
Erythema/Eschar formation	24 h	1	1	2
	48 h	0	0	1
	72 h	0	0	0
	Total (24, 48 and 72 hours)	1	1	3
	Mean (24, 48 and 72 hours)	0.3	0.3	1

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
		A9134/Female	A9149/Female	A9150/Female
Oedema formation	24 h	0	2	2
	48 h	0	0	0
	72 h	0	0	0
	Total (24, 48 and 72 hours)	0	2	2
	Mean (24, 48 and 72 hours)	0	0.7	0.7

Note

A9134: slight dryness between D2 and D5

A9149: slight dryness between D2 and D3, D6 and D10; D13 and D14

A9150: slight dryness at D3 between D6 and D10; D13 and D14

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 the skin according to the Annex I of the Regulation EC No. 1272/2008 (CLP) 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. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated during 4 hours.

It was noted, 24 hours after the test item application, on the treated area, a slight to well defined erythema associated with a slight oedema in two animals. The oedematous reactions were totally reversible at D2 and the erythematous reactions were totally reversible between D2 and D3. On the cutaneous structure, slight dryness was noted on the treated area, from D2 in two animals and from D3 in the last one. Slight dryness was still noted at the end of the observation time (D14) in two animals.

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 0.3 / 0.3 / 1 for erythema and 0.0/ 0.7/ 0.7 for oedema.

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

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