4-phenylbutan-2-one

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-11-08 to 1988-11-15

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted under GLP according to principles equivalent to those of the official OECD guideline No 404. The observation period was only 7 days compared to 14 days requested in the guideline, so that full reversibility could not be shown for all animals. In addition, the environmental conditions were not in accordance with the guidelines due to a failing heating equipment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-phenylbutan-2-one

EC Number:

219-847-4

EC Name:

4-phenylbutan-2-one

Cas Number:

2550-26-7

Molecular formula:

C10H12O

IUPAC Name:

4-phenylbutan-2-one

Test material form:

not specified

Details on test material:

No detailed information provided, test material was stored in the dark at 4 °C when not in use

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gorseside Rabbits, Northchurch, Berkhamsted, Herfordshire, UK
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: approximately 2 kg
- Housing: grid bottomed metal cages
- Diet (e.g. ad libitum): antibiotic free rabbite diet (SQC standard rabbit pellets, Special Diets Services, Witham, Essex) ad libitum
- Water (e.g. ad libitum): drinking water via automatic nozzles ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 5 to 24 °C; system was set to maintain temperatures between 17 and 23 °C but the heating equipment failed during the acclimatisation period; temperature was normally greater than 14 °C
- Humidity (%): 37 to 68
- Air changes (per hr): no reported
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL aliquots of neat substance were applied onto the skin

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

4 female rabbits

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm2
- % coverage: 100% since the substance was evenly distributed over a 2.5 cm square of surgical lint
- Type of wrap if used: Elastoplast elastic adhesive bandage 10 cm wide

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated sites were cleansed by gentle swabbing with cotton wool soaked in warm water
- Time after start of exposure: 4 hours

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

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

Reaction to treatment considered to fall mid-way between the points described was scored as a fraction (i.e. 0.5, 1.5, 2.5, etc).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 208

Time point:

other: mean of 24, 48 and 72-hour readings

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

edema score

Basis:

animal: 208

Time point:

other: mean of 24, 48 and 72-hour readings

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal: 214

Time point:

other: mean of 24, 48 and 72-hour readings

Score:

0.5

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal: 214

Time point:

other: mean of 24, 48 and 72-hour readings

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 5

Irritation parameter:

erythema score

Basis:

animal: 216

Time point:

other: mean of 24, 48 and 72-hour readings

Score:

2

Max. score:

4

Reversibility:

other: considered to be reversible after 14 days because at the last reading point of 7 days the score was below grade 1 (grede 0.5)

Results 6

Irritation parameter:

edema score

Basis:

animal: 216

Time point:

other: mean of 24, 48 and 72-hour readings

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

erythema score

Basis:

animal: 222

Time point:

other: mean of 24, 48 and 72-hour readings

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

edema score

Basis:

animal: 222

Time point:

other: mean of 24, 48 and 72-hour readings

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritant / corrosive response data:

The rabbit 216 was the most sensitive of the four tested animals showing an erythema and oedema reaction after topical application of the test substance. Erythema scores were not exceeding a value of 2 at any timepoint for this animal 216 and were lower for all other animals (the maximum erythema score was 4). Oedema scores were not exceeding a value of 0.5 for this animal 216 or for any other animal tested (the maximum oedema score was 4).

Other effects:

No other effects were observed

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The scoring of skin reaction in all four tested animals supports the view that the substance is non-irritating to the rabbit skin. The substance is considered non-irritating to rabbit skin.

Executive summary:

The irritation potential of the substance 4-phenylbutan-2-one was assessed in a GLP study following principles of the OECD guideline No. 404, however, with an observation period of 7 days instead of 14 days. Animals aged 10 to 12 weeks and weighing approximately 2 kg were used in the test. Rabbits received standard rabbit pellets and drinking water ad libitum throughout the study. The day before dosing started the dorsal surfaces of the rabbits' trunks were clipped free of hair. On the day of treatment an aliquot of 0.5 mL of the neat substance was evenly distributed over a 2.5 cm square of surgical lint, which was then placed onto the animal's skin immediately caudal to the last rib with the test material in contact with the skin. The lint patches were held in place by encircling the trunk of the animal with a length of "Elastoplast" elastic adhesive bandage 10 cm wide. After four hours of exposure the patches were removed and the application sites were cleansed by gentle swabbing with cotton wool soaked in warm water. Scorings for erythema, oedema and other observations were done at 1, 24, 48, 72 hours and 7 days. The mean erythema and oedema scores obtained from the gradings at 24, 48 and 72 hours were equal to or less than 2 in all four animals. In addition, the skin reactions were fully reversible within a period of 7 days in three animals. One animal showed very slight erythema at day 7 so that no full reversibility could be demonstrated for this effect. No other adverse effects associated with dermal exposure to the substance were reported. It was concluded that the substance is non-irritating to the skin of rabbits and that it does not fulfil the criteria for classification.