4-methylpent-3-en-2-one

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-methylpent-3-en-2-one

EC Number:

205-502-5

EC Name:

4-methylpent-3-en-2-one

Cas Number:

141-79-7

Molecular formula:

C6H10O

IUPAC Name:

4-methylpent-3-en-2-one

Details on test material:

- Name of test material (as cited in study report): Mesityl Oxide
- Physical state: liquid
- Analytical purity: 99.87%
- Purity test date: 16 April 2010
- Lot/batch No.: A1YB3N010101
- Expiration date of the lot/batch: 16 April 2012
- Storage condition of test material: Ambient condition

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan England, Hillcrest, Dodgeford Lane, Belton, Loughborough, Leicestershire, LE12 9TE, England.
- Age at study initiation: approximately 15 to 17 weeks
- Weight at study initiation: 3.06 to 3.33 kg
- Housing: 1/cage; grid-bottomed metal cages suspended over trays measuring 48x41x63 cm
- Diet (e.g. ad libitum): ad libitum - STANRAB (P) SQC, Special Diets Services, Witham, Essex CM8 3AD, UK
- Water (e.g. ad libitum): ad libitum - Tap water
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): aproximately 15 to 25
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 6 to 22 June 2010

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipping

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/site; 1 site/animal
- Concentration (if solution): as supplied

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: the test item was spread evenly over a square gauze measuring 2.5x2.5 cm.
The square gauze was then placed onto the animal’s skin with the test item in direct contact with the skin.
A strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage, this forming a semi-occlusive barrier.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): swabbing of the skin with cotton wool soaked with lukewarm water.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale
Erythema and eschar formation
0 - No erythema
1 -Slight erythema
2 - Well defined erythema
3 - Moderate to severe erythema
4 - Severe erythema (beef redness) to eschar formation preventing grading of erythema

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 (raised approximately 1mm)
4 - Severe oedema (raised more than 1 mm and extending beyond the area of exposure

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24 to 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Score of 1 recorded also 7 days after treatment; see histopathology

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24 to 72 hours

Score:

0

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Presence of desquamation 7 and 14 days after treatment; see histopathology

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24 to 72 hours

Score:

1.3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Score of 1 or 3 recorded respectively 7or 14 days after treatment; see histopathology

Results 4

Irritation parameter:

edema score

Basis:

animal: # 1, 2 and 3

Time point:

other: 24 h to 14 days

Score:

0

Max. score:

4

Irritant / corrosive response data:

Reaction at the treatment site was recorded in the following three animals:

Rabbit no. 80720001: slight erythema (score of 1) was recorded from 24 hours to 7 days after dosing. No reaction was observed on Day 15. No oedema was observed.
The calculated mean erythema and oedema scores over 24, 48 and 72 hours were 1.0 and 0.0, respectively.

Rabbit no. 80720003: No erythema or oedema (score 0) occurred at the treatment site up to 72 hours after dosing. Desquamation of the treatment site was recorded on Days 8 and 15. No oedema was observed.
The calculated mean erythema and oedema scores over 24, 48 and 72 hours were 0.0.

Rabbit no. 80720005: Well defined erythema (score of 2) was recorded 1 and 24 hours after dosing. Slight erythema (score of 1) at 48 hours, 72 hours and 7 days. Moderate to severe erythema (score of 3) was finally recorded on Day 15. No oedema was observed.
The calculated mean erythema and oedema scores over 24, 48 and 72 hours were 1.3 and 0.0, respectively.

Other effects:

Macroscopic observations
The treatment site showed multiple scabs (up to 1x1 mm) in the female no. 3 and multiple red areas in the cutis (up to 25x8 mm) were noted in the female no. 5, while no macroscopic change at the treatment site was noted in female no. 1.

Microscopic observations
The histopathological evaluation of the above-mentioned treatment sites revealed in female no. 1 focal slight acute inflammation in the dermis and in the female no. 80720003 focal scabs and chronic inflammatory reaction in the dermis.
Female no. 80720005 showed a most relevant pathological change in the treatment site such as multifocal mild haemorrhage associated to hyperplasia of follicular basal cell (hair follicles) and squamous cell layer with acanthosis of the epidermis.
As reported in the literature, the follicular basal cell hyperplasia may be considered to contribute to repair the epidermal wounding.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information based on the histopathological examinations Criteria used for interpretation of results: expert judgment

Conclusions:

These results indicate that the test item, Mesityl oxide, has an irritant effect on the skin of the rabbit following a 4 hour dermal exposure period, even though with a high individual variability. Reaction was moderately stronger in one animal and recovery was not completed in two animals at the end of the 14-day observation period.

Executive summary:

The acute dermal irritation of Mesityl oxide (purity 99.87%) was investigated in the rabbit in an OECD 404 study. A 0.5 mlaliquot of the substance was applied to the clipped dorsal skin of 3 animals for a period of 4 hours. The resulting reaction to treatment was assessed approximately 1, 24, 48, 72 hours, 7 and 14 days after the end of the exposure period. In the first rabbit slight erythema (score of 1) was recorded from 24 hours to 7 days after dosing. No reaction was observed on Day 15 (calculated mean erythema score over 24, 48 and 72 hours equal to 1.0). No oedema was observed. In the second rabbit, no erythema or oedema (scores of 0) occurred at the treatment site up to 14 days after dosing. Desquamation of the treatment site was recorded on Days 8 and 15. In the third rabbit, well defined erythema (score of 2) was recorded 1 and 24 hours after dosing, slight erythema (score of 1) at 48 hours, 72 hours and 7 days. Moderate to severe erythema (score of 3) was finally recorded on Day 15 (calculated mean erythema score over 24, 48 and 72 hours equal to 1.3). No oedema was observed. There was no indication of a systemic effect of treatment. Body weight changes were not remarkable. The histopathological evaluation of the treatment sites revealed, a focal and slight acute inflammation in the dermis in the 1^stfemale, focal scabs and chronic inflammatory reaction in the dermis in the 2^ndfemale and a multifocal and mild haemorrhage associated to hyperplasia of follicular basal cell (hair follicles) and squamous cell layer with acanthosis of the epidermis in the 3^rdfemale. As reported in the literature, the follicular basal cell hyperplasia may be considered to contribute to repair the epidermal wounding. These results indicate that the test item, Mesityl oxide, has an irritant effect on the skin of the rabbit following a 4-hour dermal exposure period, even though with a high individual variability. Reaction was moderately stronger in one animal and recovery was not completed in two animals at the end of the 14-day observation period.