4-(2-aminoethyl)phenol

Eye irritation

Administrative data

Endpoint:

eye 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:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

The objective of the study was to assess the irritant and/or corrosive effects of Phenethyl phenyl acetate (CAS No. 102-20-5) on eye, when exposed by the ocular route in rabbits.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Phenethyl phenyl acetate

IUPAC Name:

Phenethyl phenyl acetate

Constituent 2

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
- Substance type: Organic
- Physical state: Colorless Liquid
- 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 was disposed as per internal SOPs.

Specific details on test material used for the study:

- Name of test material (as cited in study report): Phenethyl phenyl acetate
- Molecular formula : C16H16O2
- Molecular weight : 240.30 g/mol
- Substance type: Organic
- Physical state: Colorless Liquid
- 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 was disposed as per internal SOPs.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: Male
- Source: Procured from LIVEON BIOLABS PVT. LTD.
- Age at study initiation: 3.0 to 4.5 Months (Approximately)
- Weight at study initiation: Minimum: 1.822 kg and Maximum: 2.146 kg (Prior to Treatment)
- Health Status : Healthy young adult animals were used for the study.
- 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 6 days (Animal No.-1) and 9 days (Animal No. 2 and 3) prior to the application of the test item.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):Minimum: 19.00 °C and Maximum: 20.80 °C
- Humidity (%):Minimum: 45.10 % and Maximum: 65.80 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 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:

24 hrs

Observation period (in vivo):

All the treated animals were observed at 1, 24, 48 and 72 hours after instillation of test item

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye of rabbit was washed with normal saline.
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize Method

TOOL USED TO ASSESS SCORE: Ophthalmoscope and fluorescent strips.

Results and discussion

In vitro

Other effects / acceptance of results:

no data available

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1,#2 and #3

Time point:

other: 24,48,72 hrs and 7 days

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

Untreated (Control Eye)

Results 2

Irritation parameter:

iris score

Basis:

animal: #1,#2 and #3

Time point:

other: 24,48,72 hrs and 7 days

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

Untreated (Control Eye)

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: #1,#2 and #3

Time point:

other: 24,48,72 hrs and 7 days

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

Untreated (Control Eye)

Results 4

Irritation parameter:

chemosis score

Basis:

animal: #1,#2 and #3

Time point:

other: 24,48,72 hrs and 7 days

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

Untreated (Control Eye)

Results 5

Irritation parameter:

cornea opacity 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

Remarks:

For treated eyes

Results 6

Irritation parameter:

iris score

Basis:

animal: #1,#2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

For treated eyes

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal: #1,#2 and #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

For treated eyes

Results 8

Irritation parameter:

chemosis 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

Remarks:

For treated eyes

Irritant / corrosive response data:

The following were observed in treated rabbits.
Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals.

Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: No swelling (normal) was observed in all the animals.

At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals.

Observation at 48 and 72 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis: No swelling (normal) was observed in all the animals.

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site) for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively.

Other effects:

Clinical Observation
No systemic toxicity was observed in treated rabbits during the experimental period

Mortality
No mortality was observed during the experimental period.

Body weight
Increase in body weights in all the treated animals at termination when compared to day 0 was observed.

Any other information on results incl. tables

Table 1: Individual Animal Eye Irritation Scores

In Treated area Dose: 0.1 ml of as such test item                                                 Sex: Male

Animal Numbers	1					2					3
Application Side	Right					Right					Right
Eye Reactions	At hour					At hour					At hour
	*	1	24	48	72	*	1	24	48	72	*	1	24	48	72
Corneal Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Area of Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctiva	0	1	1	0	0	0	1	1	0	0	0	1	1	0	0
Chemosis	0	1	0	0	0	0	1	0	0	0	0	1	0	0	0
Corneal Damage%	0	./.	0			0	./.	0			0	./.	0

In Treated area Dose: Untreated                                                                             Sex: Male

Animal Numbers	1					2					3
Application Side	Right					Right					Right
Eye Reactions	At hour					At hour					At hour
	*	1	24	48	72	*	1	24	48	72	*	1	24	48	72
Corneal Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Area of Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctiva	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Chemosis	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Corneal Damage%	0	./.	0			0	./.	0			0	./.	0

Key: *= Pre-exposure eye examination.

      ./.= Not Applicable

Eye Irritation Scores - Mean Values after 24, 48, 72 Hours (Treated eye)

Animal No.  Eye Reaction	1	2	3
Corneal Opacity	0.00	0.00	0.00
Iris	0.00	0.00	0.00
Conjunctiva	0.33	0.33	0.33
Chemosis	0.00	0.00	0.00

Eye Irritation Scores - Mean Values after 24, 48, 72 Hours (Untreated eye)

Animal No.  Eye Reaction	1	2	3
Corneal Opacity	0.00	0.00	0.00
Iris	0.00	0.00	0.00
Conjunctiva	0.00	0.00	0.00
Chemosis	0.00	0.00	0.00

Formula :

Mean Eye Irritation Score = Sum of the Individual Animal Score for eye reaction at 24, 48 and 72 hours

Number of the Observations (3)

Table 2 : Individual Animal Clinical Signs

Animal No.	Days (Post application observation)
	0	1	2	3
1	1	1	1	1
2	1	1	1	1
3	1	1	1	1

Key: 1 = Normal

Table 3: Individual Animal Body Weight

Animal No.	Animal Body Weight (kg)
	Prior to application	At termination
1	2.146	2.180
2	2.146	2.198
3	1.822	1.886

Key: kg = Kilogram

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

The overall irritation index of 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid was 1.25 after 72 hours.Also, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid did not produce any clinical signs of toxicity throughout the examination period of 21 days.
Hence, under the test conditions, 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid can be concluded to be not irritating to New Zealand White rabbit eyes.

Executive summary:

Acute Eye Irritation/Corrosion Study of Phenethyl phenyl acetate (CAS No. 102-20-5) in Rabbits, was performed in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) as per OECD guideline no. 405.

Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas; 0.1 ml of test item (as such)was instilled in the other (treated) eye of rabbits. The eye was observed at 1, 24, 48, 72 hours after test item instillation. Ophthalmoscope was used for scoring of eye lesions.In the initial test,0.1 ml of as such test item was instilled into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions hence a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3);0.1 ml of as such test item was instilled into the conjunctival sac of right eye of both the rabbits and left eye served as the control.

Untreated eye of all the three rabbits was normal throughout the experimental period of 72 hours.

The following grading scores were observed in treated eye of tested rabbits.

Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all the animals. Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in all the animals; Chemosis: No swelling (normal) was observed in all the animals. At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0% damage in all the animals. Observation at 48 and 72 hours after instillation of test item revealed: Cornea- No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Blood vessels normal in all the animals; Chemosis: No swelling (normal) was observed in all the animals.

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours (at treated site) for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 0.33, 0.00; 0.00, 0.00, 0.33, 0.00 and 0.00, 0.00, 0.33, 0.00 respectively.

Under the experimental conditions tested, Phenethyl phenyl acetate (CAS No. 102-20-5) is found to be Non Irritant to New Zealand White male rabbit eyes and is thus Classified as “Category- Not Classified as Eye Irritant” as per CLP criteria for Classification.