2-Oxetanone, 3-C14-16-alkyl 4-C15-17-alkylidene derivs.

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

24 August 1998 - 4 September 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to internationally accepted guidelines and under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

849705-80-2

Cas Number:

849705-80-2

IUPAC Name:

849705-80-2

Constituent 2

Reference substance name:

-

EC Number:

434-710-0

EC Name:

-

IUPAC Name:

434-710-0

Details on test material:

Identity: P-2290
Chemical name: 2-Oxetanone, 3-(C14-16 and C16-unsatd. branched and linear alkyl) 4-(C15-17 and C17-unsatd. branched and linear alkylidene) derivs
Appearance: Brown waxy liquid
Storage conditions: 4°C in the dark
Batch number: No data
Composition: Alkyl ketene dimer > 85%, Toluene <20ppm
Sample receive: 8 May 1998

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: 13 weeks
- Weight at study initiation: 2.4-2.8
- Housing: They were housed individually in stainless steel cages with perforated floors in Building R14 Room 5.
- Diet (e.g. ad libitum): ad libitum, a standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 49-74
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 24 August 1998 - 4 September 1998

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml

Duration of treatment / exposure:

4 hours

Observation period:

Examination of the treated skin was made on Day 1 (ie approximately 50 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure). Additional observations were made for two animals on Days 5 through 8 and for one animal on Days 9 through 12.

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 25 mm x 25 mm
- Type of wrap if used: gauze pad covered by "Elastoplast" adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treatment site was washed with warm water (34ºC) to remove any residualtest substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema and eschar formation:
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well-defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading

Oedema formation:
0 No oedema
1 Very slight oedema (barely perceptible)
2 Slight oedema (edges of area well-defined by definite raising)
3 Moderate oedema (edges raised approximately 1 millimetre)
4 Severe oedema (raised more than 1 millirnetre and extending beyond the area of exposure)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

all animal

Time point:

other: 24-48-72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 11 days

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritant / corrosive response data:

Well-defined erythema with very slight oedema was seen in one animal. Very slight erythema alone was seen in one further animal. Desquamation of the stratum comeum (characterised by dryness and sloughing of skin) developed in both rabbits. These reactions had resolved completely by day 11 after exposure. No dermal irritation was observed in the remaining animal throughout the duration of the study.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

no.	Effect	Min.	Days after application					Mean score erythema 24/48/72 h	Mean score oedema 24/48/72 h
		50	1	2	3	7	11
1211	Erythema/ eschar Oedema	1 0	2 1	2 1	2 0	2a 0	0 0	2	0.66
1212	Erythema/ eschar Oedema	0 0	0 0	0 0	0 0			0	0
1213	Erythema/ eschar Oedema	0 0	1 0	1 0	1 0	0a 0		1	0
Mean		0.17	0.67	0.67	0.5	0.33	0	1	0.22

a Desquamation of the stratum corneum (characterized by dryness and sloughing of skin)

Applicant's summary and conclusion

Conclusions:

Based on the scores for this study the test substance is not classified for skin irritation according to OECD GHS criteria.

Executive summary:

A study was performed to assess the skin irritation potential of P-2290 to the rabbit. The method followed was that described in: EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No. L383A, 29.12.92), Part B, Method B.4. Acute toxicity (Skin Irritation).

OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion". Adopted 17 July 1992.

Three rabbits were each administered a single dermal dose of 0.5 ml of the test substance and observed for up to 11 days after exposure. A single semi-occlusive application of P-2290 to intact rabbit skin for four hours elicited very slight to well-defined dermal erythema and slight oedema. Based on the scores for this study the test substance is not classified for skin irritation according to OECD GHS criteria.