Phenethyl phenylacetate

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

Justification for type of information:

data is from experimental reports

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

The objective of the study was to assess the irritant and/or corrosive effects of the test chemical after topical application on the intact skin in rabbits.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Phenethyl phenylacetate

EC Number:

203-013-1

EC Name:

Phenethyl phenylacetate

Cas Number:

102-20-5

Molecular formula:

C16H16O2

IUPAC Name:

2-phenylethyl phenylacetate

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Phenethyl phenyl acetate
- Molecular formula : C16H16O2
- Molecular weight : 240.30 g/mole
- Substance type:Organic
- Physical state: Colorless Liquid
- Analytical purity: 99.55 %
- Lot/batch No.: 2012052101
- Storage condition of test material: Room temperature (20° - 30 °C)
- Other: Handling and Disposal
Safety precautions: Aprons, masks, caps, gloves and goggles were used to ensure the health and safety of the Personnel
Disposal:The remaining unused test item formulations were disposed as per internal SOPs

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Procured from GENTOX BIOSERVICES PVT. LTD.
- Age at study initiation: 4.0 to 5.5 Months (Approximately)
- Weight (Prior to Treatment): Minimum: 1.990 kg & Maximum: 2.186 kg
- Health Status : Healthy young adult rabbits were used for the study. Females were nulliparous and non-pregnant.
- Housing: The animals were housed individually in stainless steel cages.
- Room Sanitation: The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle: All the cages and water bottles were changed minimum twice a week.
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rabbit diet, ad libitum.
- Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum.
- Acclimation period: Rabbits were acclimatised to the test conditions for a period of 10 days (Animal No.-1) and 13 days (Animal No.-2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 19.00 °C and Maximum: 21.40 °C
- Humidity (%):Minimum: 41.90 % and Maximum: 65.80 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 ml
- Concentration (if solution):N/A

VEHICLE
- Amount(s) applied (volume or weight with unit):N/A
- Concentration (if solution):N/A
- Lot/batch no. (if required):N/A
- Purity:N/A

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 female rabbits

Details on study design:

TEST SITE
- Area of exposure: The dorsal lumbar region at contralateral sites.
- % coverage: Approximately 6 X 6 cm.
- Type of wrap if used: A porous gauze dressing and non-irritating tape (Micropore 3”).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The residual test item was removed by using cotton soaked in distilled water.
- Time after start of exposure: 4 hour

SCORING SYSTEM: Draize Method

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: At 1 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 hrs

Remarks on result:

other: Very slight erythema (barely perceptible)

Results 2

Irritation parameter:

erythema score

Basis:

animal: #1 ,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

animal: #1 ,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The following were observed in treated rabbits.
The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per draize method.

Animal No. 1, showed no erythema and oedema at 1, 24, 48 and 72 hours of observation. In animal no. 2, at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema whereas animal no. 3 showed no erythema and oedema. At 24, 48 and 72 hours, animal nos. 2 and 3 showed no erythema and no oedema.The other untreated side revealed no erythema and no oedema and was found to be normal throughout the experimental period. The individual mean score at 24, 48 and 72 hours for treated site for animal nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively

Other effects:

Clinical Observation
No systemic toxicity was observed at treated rabbits during the experimental period
Mortality
No mortality was observed during the observation period
Body weights
Increase in body weight at terminal sacrifice as compared to day 0 in all the three animals was observed

Any other information on results incl. tables

Table 1: Skin Reaction

In Treated area Dose: 0.5 ml of test item (as such, undiluted)                              Sex: Female

Animal No.	Test	Treated  area	Erythema score				Oedema score
			1h	24h	48h	72h	1h	24h	48h	72h
1	Initial	Right	0	0	0	0	0	0	0	0
2	Confirmatory	Left	1	0	0	0	0	0	0	0
3		Right	0	0	0	0	0	0	0	0

In Control area Dose: 0.5 ml of distilled water                                                        Sex: Female

Animal No.	Test	Treated area	Erythema score				Oedema score
			1h	24h	48h	72h	1h	24h	48h	72h
1	Initial	Left	0	0	0	0	0	0	0	0
2	Confirmatory	Right	0	0	0	0	0	0	0	0
3		Left	0	0	0	0	0	0	0	0

Key: h = Hour.

Erythema                                                                                                       Oedema

0 =No erythema                                                                                           0 =No oedema

1 = Very slight erythema(barely perceptible)

Mean Individual Animal Score at 24, 48 and 72 hours (Treated Site)

Animal Number                   Observations	1	2	3
Erythema	0.00	0.00	0.00
Oedema	0.00	0.00	0.00

Table 2: Individual Animal Body Weight

Sex: Female

Animal No.	Body Weight (kilogram)
	Prior to Dosing	At termination
1	2.136	2.178
2	1.990	2.080
3	2.186	2.240

Table 3: Individual Animal Clinical Signs

Sex: Female

Animal No.	Days (Post dosing Observation)
	0	1	2	3
1	1	1	1	1
2	1	1	1	1
3	1	1	1	1

Key: 1 = Normal

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

No erythema and no oedema (skin irritation) were found at the end of 72 hour observation period after patch removal.The individual mean score at 24, 48 and 72 hours for treated site for animal nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively. Hence, it was concluded that the test chemical was Non-Irritating to the skin of Female New Zealand White rabbits under the experimental conditions tested and can be Classified under the category "Not Classified” as per CLP criteria for Classification.

Executive summary:

Acute Dermal Irritation/corrosion Study of the test chemical in Rabbits, was performed as per OECD guideline No. 404. Three healthy young adult New Zealand White female rabbits were used for conducting acute dermal irritation/corrosion study. Body weights were recorded on day 0 (prior to application) and at termination. Rabbits with good intact skin were selected for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of 0.5 ml test chemical was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits.The other untreated side was kept as control area and 0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test chemical application site was wiped with water without altering the integrity of the epidermis.Initially, the test chemical was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in animal no.1, no erythema and oedema was observed at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and no oedema was observed. Hence the confirmatory test was conducted on additional two rabbits (No. 2 and 3) to confirm the non irritant nature of the test chemical. The patch was removed after 4 hours and rabbits were observed for erythema and oedemaat 1, 24, 48 and 72 hours after patch removal, evaluatedand graded as per Draize method. In animal no. 2, at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema whereas animal no. 3 showed no erythema and oedema. At 24, 48 and 72 hours, animal nos. 2 and 3 showed no erythema and no oedema. The other untreated side revealed no erythema and no oedema and was observed to be normal throughout the experimental period. No erythema and no oedema (skin irritation) were observed at the end of 72 hour observation period after patch removal.The individual mean score at 24, 48 and 72 hours for treated site for animal nos. 1, 2 and 3 were 0.00, 0.00, 0.00 and 0.00, 0.00, 0.00, for erythema and oedema formation, respectively. Hence, it was concluded that the test chemical was Non-Irritating to the skin of Female New Zealand White rabbits under the experimental conditions tested and can be Classified under the category "Not Classified” as per CLP criteria for Classification.