1-phenylethanol

Endpoint summary

Description of key information

Skin irritation:

The individual mean score at 24, 48 and 72 hours 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 1-phenylethanol (CAS No. - 98-85-1) was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested and being classified as “Not Classified” as per CLP Classification.

Eye Irritation:

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 2.00, 1.00; 0.00, 0.00, 1.33, 1.00, and 0.00, 0.00, 2.00, 1.00, respectively.

Under the experimental conditions tested, all the three animals were fully reversible within an observation period of 14 for animal no. 2. and 21 days for animal no. 1 and 3. Hence, under the experimental test conditions, 1-phenylethanol [CAS: 98-85-1] was considered to be an eye irritant. It was further classified under the category "Category 2".

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

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 1-phenylethanol (CAS No. - 98-85-1) after dermal application on the intact skin in rabbits.

GLP compliance:

yes

Specific details on test material used for the study:

- IUPAC name: 1-phenylethan-1-ol
- Common Name: 1-Phenylethanol
- Mol. formula: C8H10O
- Molecular Weight: 122.166 g/mole
- InChI: 1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3
- Smiles: c1(ccccc1)C(C)O
- Substance type: Organic
- Physical state: Clear colourless liquid
- Analytical purity: 99.62%
- Lot/batch No.: 2014022801R-434
- 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 and the same was documented in the raw data

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Procured from LIVEON BIOLABS PVT. LTD.
- Sex: Male
- Health Status: Healthy young adults rabbits were used for the study.
- Age at study initiation: 4.5 to 5.0 Months (Approximately)
- Weight at study initiation: Minimum: 1.766 kg and Maximum: 2.332
- Housing: The animals were housed individually in stainless steel cages
- Diet (e.g. ad libitum): All animals were provided conventional laboratory rabbit diet (Nutrivet Life Sciences) ad libitum. Batch No. 200004
- 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 8 days (Animal No.-2 and 3) prior to the application of the test item
- Identification: During acclimatization marking was done with non toxic marker pen in the inside of left ear of rabbits and after acclimatization, animals were marked with permanent number in the inner side of right ear of rabbits. Permanent marker and cage card was used for identification. The individual cage cards were labelled with at least study no., study type, test system, sex, dose, experiment start date and experiment completion date.
- 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

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 20.30°C and Maximum: 22.70 °C
- Humidity (%): Minimum: 48.30 % and Maximum: 68.30 %
- Air changes (per hr): More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

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
VEHICLE: Not applicable

Duration of treatment / exposure:

4-hour exposure period

Observation period:

1, 24, 48 and 72 hrs

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 6 X 6 cm at contralateral sites
- Type of wrap if used: porous gauze dressing and non-irritating tape (Micropore 3”)

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

Control site: 0.5 ml distilled water was applied at control site.

SCORING SYSTEM: Draize Method

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

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 patch was removed after 4 hours and rabbits were observed for erythema and edema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per draize method.
Animal No. 1, showed very very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and no oedema was observed in animal no 1.
Animal No. 2 and 3 showed very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and no oedema was observed in animal no. 2 and 3
The individual mean score at 24, 48 and 72 hours 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 weight
All rabbits showed increased in body weight at termination when compared to day 0.

Table 1: Skin Reaction

In Treated area Dose:0.5 ml of test item                                                                          Sex: Male

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

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

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	0	0	0	0	0	0	0	0
3		Right	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)                 1 =Very slight oedema (barely perceptible)

2 =Well defined erythema                                                  2 = Slight oedema (edges of area well defined by definite raising)

Mean Individual Animal Score at 24, 48 and 72 hours

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

Animal No.	Body Weight (kg)
	Prior to Dosing	At termination
1	1.766	1.820
2	1.998	2.110
3	2.332	2.378

Table 3: Individual Animal Clinical Signs

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

Interpretation of results:

other: not irritating

Conclusions:

The individual mean score at 24, 48 and 72 hours 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 1-phenylethanol (CAS No. - 98-85-1) was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested and being classified as “Not Classified” as per CLP Classification.

Executive summary:

Acute Dermal Irritation/corrosion Study of 1-phenylethanol[CAS: 98-85-1] in Rabbits, was performed as per OECD guideline No. 404.  Three healthy young adult male New Zealand White 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 of test item (as such) 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 item application site was wiped with water without altering the integrity of the epidermis.

Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. Very slight erythema (barely perceptible) and very slight oedema (barely perceptible) was observed in animal No. 1 at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and no oedema was observed in animal no 1. Hence the confirmatory test was conducted on additional two rabbit (no. 2 and 3) to confirm the non irritant nature of the test item. 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.

At 1 hour very slight erythema (barely perceptible) and very slight oedema (barely perceptible) was observed in all 3 animals. At 24, 48 and 72 hours observation no erythema and no oedema was observed in all 3 animals.

The individual mean score at 24, 48 and 72 hours 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 1-phenylethanol (CAS No. - 98-85-1) was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested and being classified as “Not Classified” as per CLP Classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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 “1-phenylethanol (CAS No. - 98-85-1)” on eye, when exposed by the ocular route in rabbits.

GLP compliance:

yes

Specific details on test material used for the study:

- IUPAC name: 1-phenylethan-1-ol
- Common Name: 1-Phenylethanol
- Mol. formula: C8H10O
- Molecular Weight: 122.166 g/mole
- InChI: 1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3
- Smiles: c1(ccccc1)C(C)O
- Substance type: Organic
- Physical state: Clear colourless liquid
- Analytical purity: 99.62%
- Lot/batch No.: 2014022801R-434
- 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 and the same was documented in the raw data

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Procured from LIVEON BIOLABS PVT. LTD.
- Sex: Female
- Age at study initiation: 4.5 to 5.0 Months (Approximately)
- Weight at study initiation: Minimum: 2.102 kg and Maximum: 2.652 kg
- Health Status: Healthy young adult rabbits were used. 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 (Nutrivet Life Sciences) ad libitum. Batch No.: 200004.
- 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 7 days (Animal No.-1) and 9 days (Animal No. 2 and 3) prior to the application of the test item.
- Identification: During acclimatization marking was done with non toxic marker pen in the inside of left ear of rabbits and after acclimatization, animals were marked with permanent number in the inner side of right ear of rabbits. Permanent marker and cage card was used for identification. The individual cage card was labelled with at least study no., study type, test system, sex, dose, experiment start date and experiment completion date.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Minimum: 18.90°C and Maximum: 22.70 °C
- Humidity (%): Minimum: 48.30% and Maximum: 68.30%
- Air changes (per hr):More than 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12:12

Vehicle:

unchanged (no vehicle)

Controls:

other: yes, one eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): N/A

VEHICLE: N/A

Duration of treatment / exposure:

24 hr

Observation period (in vivo):

day 14 (for animal no. 2 ) and day 21 (for animal no. 1 and 3)

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

3 females

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 hrs

SCORING SYSTEM: Grading of irritation lesions was carried out as per Draize Method

TOOL USED TO ASSESS SCORE: ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 21 days

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 21 days

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

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 was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) in animal no. 2 and obvious swelling with partial eversion of lids in animal no. 1 and 3.
Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was seen in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in all the animals.
At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 30%, 30% and 20% damage in animal no. 1, 2 and 3 respectively.
Observation at 48 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was observed in animal no. 1 and 3 whereas some blood vessels definitely hyperaemic (injected) was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all 3 animals.
Observation at 72 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was observed in animal no. 1 and 3 whereas some blood vessels definitely hyperaemic (injected) was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all 3 animals.
Observation on day 7 after instillation of test item revealed: Cornea- No ulceration or opacity was seen 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 animal no. 1 and 3 and no swelling (Normal) in animal no. 2.
Observation on day 14 after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was observed in animal no.1 and 3 whereas no ulceration or opacity in animal no. 2; Area of Opacity- One quarter (or less) but not zero was observed in animal no. 1 and 3 whereas zero was observed in animal no.2; Iris: Normal in all the animals; Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in animal no.1 and 3 whereas blood vessels normal was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in animal no. 1 and 3 whereas no swelling (Normal) was observed in animal no. 2. Animal no. 2 recovered on day 14.
Observation on day 21 after instillation of test item revealed: Cornea- No ulceration or opacity was observed in animal no. 1 and 3; Area of Opacity- Zero was observed in animal no. 1 and 3; Iris: Normal in all the animals; Conjunctivae - Blood vessels normal was observed in animal no. 1 and 3; Chemosis: No swelling (Normal) was observed in animal no. 1 and 3.

Other effects:

Clinical Observation
No systemic toxicity was observed in treated rabbits during the experimental period.
Mortality
No mortality was observed during the observation period.
Body weight
Increase in body weights of all the animals weighed on test day 0 (prior to application) and at termination (when compared to day 0)

Table 1 : Individual Animal Eye Irritation Scores

In Treated area Dose: 0.1 ml of test item (as such)                                               Sex: Female

Animal Number	1
Application Side	Right
Eye Reactions	*	Hour(s)				Day
		1	24	48	72	7	14	21
Cornea	0	0	0	0	0	0	1	0
Area of Opacity	0	0	0	0	0	0	1	0
Iris	0	0	0	0	0	0	0	0
Conjunctiva	0	2	2	2	2	1	1	0
Chemosis	0	2	1	1	1	1	1	0
Corneal Damage (%)	30

Animal Number	2
Application Side	Right
Eye Reactions	*	Hour(s)				Day
		1	24	48	72	7	14
Cornea	0	0	0	0	0	0	0
Area of Opacity	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0
Conjunctiva	0	2	2	1	1	1	0
Chemosis	0	1	1	1	1	0	0
Corneal Damage (%)	30

Animal Numbers	3
Application Side	Right
Eye Reactions	*	Hour(s)				Day
		1	24	48	72	7	14	21
Cornea	0	0	0	0	0	0	1	0
Area of Opacity	0	0	0	0	0	0	1	0
Iris	0	0	0	0	0	0	0	0
Conjunctiva	0	2	2	2	2	1	1	0
Chemosis	0	2	1	1	1	1	1	0
Corneal Damage (%)	20

Key:*= Pre-treatment eye examination

Dose: Untreated (Control Eye)                                                                       Sex:Female

Animal Number	1
Application Side	Left
Eye Reactions	*	Hour(s)				Day
		1	24	48	72	7	14	21
Cornea	0	0	0	0	0	0	0	0
Area of Opacity	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0
Conjunctiva	0	0	0	0	0	0	0	0
Chemosis	0	0	0	0	0	0	0	0
Corneal Damage (%)	0

Animal Number	2
Application Side	Left
Eye Reactions	*	Hour(s)				Day
		1	24	48	72	7	14
Cornea	0	0	0	0	0	0	0
Area of Opacity	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0
Conjunctiva	0	0	0	0	0	0	0
Chemosis	0	0	0	0	0	0	0
Corneal Damage (%)	0

Animal Number	3
Application Side	Left
Eye Reactions	*	Hour(s)				Day
		1	24	48	72	7	14	21
Cornea	0	0	0	0	0	0	0	0
Area of Opacity	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0
Conjunctiva	0	0	0	0	0	0	0	0
Chemosis	0	0	0	0	0	0	0	0
Corneal Damage (%)	0

Key:*= Pre- treatment eye examination

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	2.00	1.33	2.00
Chemosis	1.00	1.00	1.00

Formula :

Mean Eye Irritiation 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	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21
1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1
2	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	./.	./.	./.	./.	./.	./.	./.
3	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	1	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	2.652	2.932
2	2.102	2.290
3	2.614	2.780

Key: kg = Kilogram

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 2.00, 1.00; 0.00, 0.00, 1.33, 1.00, and 0.00, 0.00, 2.00, 1.00, respectively.
Under the experimental conditions tested, all the three animals were fully reversible within an observation period of 14 for animal no. 2. and 21 days for animal no. 1 and 3. Hence, under the experimental test conditions, 1-phenylethanol [CAS: 98-85-1] was considered to be an eye irritant. It was further classified under the category "Category 2".

Executive summary:

Acute eye irritation/corrosion study was conducted in rabbits to evaluate the eye irrritant nature of the test chemical 1-phenylethanol. The study was performed as per OECD 405 Guidelines using 3 female New Zealand White rabbits.

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 was instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48, 72 hour, day 7, day 14 and day 21 for animal no. 1 and 3 whereas at 1, 24, 48, 72 hour, day 7 and day 14 for animal no. 2 after test item instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test, 0.1 ml of test item (as such) was applied 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 a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1 ml of 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 were normal throughout the experimental period. Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) in animal no. 2 and obvious swelling with partial eversion of lids in animal no. 1 and 3.

Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was seen in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in all the animals.

At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 30%, 30% and 20% damage in animal no. 1, 2 and 3 respectively.

Observation at 48 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was observed in animal no. 1 and 3 whereas some blood vessels definitely hyperaemic (injected) was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all 3 animals.

Observation at 72 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was observed in animal no. 1 and 3 whereas some blood vessels definitely hyperaemic (injected) was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all 3 animals.

Observation on day 7 after instillation of test item revealed: Cornea- No ulceration or opacity was seen 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 animal no. 1 and 3 and no swelling (Normal) in animal no. 2.

Observation on day 14 after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was observed in animal no.1 and 3 whereas no ulceration or opacity in animal no. 2; Area of Opacity- One quarter (or less) but not zero was observed in animal no. 1 and 3 whereas zero was observed in animal no.2; Iris: Normal in all the animals; Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in animal no.1 and 3 whereas blood vessels normal was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in animal no. 1 and 3 whereas no swelling (Normal) was observed in animal no. 2. Animal no. 2 recovered on day 14.

Observation on day 21 after instillation of test item revealed: Cornea- No ulceration or opacity was observed in animal no. 1 and 3; Area of Opacity- Zero was observed in animal no. 1 and 3; Iris: Normal in all the animals; Conjunctivae - Blood vessels normal was observed in animal no. 1 and 3; Chemosis: No swelling (Normal) was observed in animal no. 1 and 3.

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 2.00, 1.00; 0.00, 0.00, 1.33, 1.00, and 0.00, 0.00, 2.00, 1.00, respectively.

Under the experimental conditions tested, all the three animals were fully reversible within an observation period of 14 for animal no. 2. and 21 days for animal no. 1 and 3. Hence, under the experimental test conditions, 1-phenylethanol [CAS: 98-85-1] was considered to be an eye irritant. It was further classified under the category "Category 2".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

Various studies have been summarized to determine the level of dermal irritation/ corrosion caused by 1-phenylethanol in living organisms. These studies include in vivo experimental results on rats, rabbits and humans for the target chemical.

Acute Dermal Irritation/corrosion Study of 1-phenylethanol[CAS: 98-85-1] in Rabbits, was performed as per OECD guideline No. 404.  Three healthy young adult male New Zealand White 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 of test item (as such) 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 item application site was wiped with water without altering the integrity of the epidermis.

Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. Very slight erythema (barely perceptible) and very slight oedema (barely perceptible) was observed in animal No. 1 at 1 hour of observation. At 24, 48 and 72 hours observation no erythema and no oedema was observed in animal no 1. Hence the confirmatory test was conducted on additional two rabbit (no. 2 and 3) to confirm the non irritant nature of the test item. 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.

At 1 hour very slight erythema (barely perceptible) and very slight oedema (barely perceptible) was observed in all 3 animals. At 24, 48 and 72 hours observation no erythema and no oedema was observed in all 3 animals.

The individual mean score at 24, 48 and 72 hours 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 1-phenylethanol (CAS No. - 98-85-1) was Non-Irritating to the skin of male New Zealand White rabbits under the experimental conditions tested and being classified as “Not Classified” as per CLP Classification.

This result is supported by a similar study designed and conducted to determine the dermal reaction profile of 1-phenylethan-1-ol in Wistar rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures

1-Phenylethan-1-ol[SK1] was tested in 5 females (3 females for dose range finding study followed by 2 females for main study) Wistar rats at the doses of 200, 1000 and 2000 mg/kg body weight.

Based on the individual body weight, the undiluted test item at the doses of 200 (0.20 mL/kg body weight), 1000 (1 mL/kg body weight) and 2000(1.99 mL/kg body weight) - based on the density of the test item1.004 g/cm3 was applied directly to the clipped skin of the animal to cover about 10% of the body surface of the animal (semi-occlusive). The area of application was covered with cotton gauze (size: Females: 8 x 5 cm of 6 ply) and it was secured in position by adhesive tape wound around the torso. The test item contact period with the skin was for 24 hours. After the 24 hours contact period, the dressing was removed and the applied area was washed with deionized water and wiped dry using clean towels. All the rats were observed for clinical signs of toxicity and mortality for 14 days post application. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test item using the Draize criteria. There were no clinical signs of toxicity and mortality. There was no skin reaction observed at test item applied area. Body weight was measured on days 1, 8 and 15 and all rats gained weight during experimental period. At the end of observation period, all surviving animals were euthanized and subjected to necropsy. There were no abnormalities detected at the necropsy

There was no skin reaction observed at test item applied area. The mean erythema and edema scores were 0.0 at all observation times. Hence, it was concluded that 1-phenylethan-1 -ol was Non-Irritating to the skin of Wistar rats under the experimental conditions tested and classified as “Category-Not Classified” as per CLP Classification.

These results are supported by Preliminary irritation tests performed in guinea pigs to determine the concentration of 1-Phenylethanol suitable for the sensitization study [injection challenge concentration (ICC) and application challenge concentration(ACC)].

 4 Albino Hartley guinea pigs of the same sex were injected intradermally on the shaved flanks with 0.1 ml aliquots of a range of concentrations of tests material in a suitable solvent. The reactions were examined for size (two largest diameters), erythema and oedema 24 h later and the concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC).0.1 ml of the test material in a range of concentrations in a suitable solvent were applied in small circular areas to the shaved flanks of 4 guinea pigs of the same sex.The reactions were examined for erythema 24 hours later and the highest concentration which caused no irritation was selected as the application challenge concentration (ACC).

No signs of erythema and edema were observed at 0.25% ICC and 30% ACC concentrations. Hence, 1-Phenylethanol was considered to be non-irritating on guinea pigs in the preliminary irritation tests performed for the sensitization study.

 

The above results are further supported by a Maximization pre-screen test performed on healthy male volunteers to assess the irritation potential of 1-phenylethanol.

8% 1-phenylethanol in petrolatum (5520 microgram/cm2) was applied to the backs of five healthy male volunteers for 48 hours under occlusion. The volunteers were observed for signs of irritation.

No subject had any irritation at the end of the study. Hence, 1-phenylethanol can be considered to be not irritating to human skin.

These results are also supported by the dermal irritation potential evaluation of 1-phenylethanol as a part of an acute dermal LD50 toxicity study in rabbits.

Doses were 1.25 (n = 6), 2.5 (n = 4) and 5.0 (n = 4) g/kg. All animals dosed at 5 g/kg died within 24 hours, before skin evaluation could be performed. Erythema was slight in 3/6 and 1/4 rabbits and moderate in 3/6 and 3/4 rabbits exposed to 1.25 and 2.5 g/kg, respectively of 1-phenylethanol. Edema was moderate in 5/6 and 4/4 animals exposed to 1.25 and 2.5 g/kg, respectively. No edema score was reported for the remaining animal at 1.25 g/kg.

Since, erythema and edema was observed in most of the animals tested, 1 -phenylethanol can be considered to be moderately irritating to rabbit skin.

Even though one of the studies in rabbits reports that 1-Phenylethanol could cause irritation to skin, but majority of the studies have reported that 1-Phenylethanol was rather not irritating to skin. Hence, taking into consideration the majority of the results, 1-Phenylethanol can be regarded to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, 1-phenylethanol can be classified under the category “Not Classified”.

 

Eye Irritation:

Various studies have been summarized to determine the level of ocular irritation/ damage caused by 1-phenylethanol in living organisms. These studies include in vivo experimental results on rabbits for the target chemical.

Acute eye irritation/corrosion study was conducted in rabbits to evaluate the eye irrritant nature of the test chemical 1-phenylethanol. The study was performed as per OECD 405 Guidelines using 3 female New Zealand White rabbits.

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 was instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48, 72 hour, day 7, day 14 and day 21 for animal no. 1 and 3 whereas at 1, 24, 48, 72 hour, day 7 and day 14 for animal no. 2 after test item instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test, 0.1 ml of test item (as such) was applied 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 a confirmatory test was conducted on additional two rabbits (animal no. 2 and 3); 0.1 ml of 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 were normal throughout the experimental period. Observation at 1 hour after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) in animal no. 2 and obvious swelling with partial eversion of lids in animal no. 1 and 3.

Observation at 24 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was seen in all the animals; Chemosis: Some swelling above normal (includes nictitating membranes) was seen in all the animals.

At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 30%, 30% and 20% damage in animal no. 1, 2 and 3 respectively.

Observation at 48 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was observed in animal no. 1 and 3 whereas some blood vessels definitely hyperaemic (injected) was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all 3 animals.

Observation at 72 hours after instillation of test item revealed: Cornea- No ulceration or opacity was seen in all the animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals; Conjunctivae - Diffuse, crimson color; individual vessels not easily discernible was observed in animal no. 1 and 3 whereas some blood vessels definitely hyperaemic (injected) was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in all 3 animals.

Observation on day 7 after instillation of test item revealed: Cornea- No ulceration or opacity was seen 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 animal no. 1 and 3 and no swelling (Normal) in animal no. 2.

Observation on day 14 after instillation of test item revealed: Cornea- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible was observed in animal no.1 and 3 whereas no ulceration or opacity in animal no. 2; Area of Opacity- One quarter (or less) but not zero was observed in animal no. 1 and 3 whereas zero was observed in animal no.2; Iris: Normal in all the animals; Conjunctivae - Some blood vessels definitely hyperaemic (injected) was observed in animal no.1 and 3 whereas blood vessels normal was observed in animal no. 2; Chemosis: Some swelling above normal (includes nictitating membranes) was observed in animal no. 1 and 3 whereas no swelling (Normal) was observed in animal no. 2. Animal no. 2 recovered on day 14.

Observation on day 21 after instillation of test item revealed: Cornea- No ulceration or opacity was observed in animal no. 1 and 3; Area of Opacity- Zero was observed in animal no. 1 and 3; Iris: Normal in all the animals; Conjunctivae - Blood vessels normal was observed in animal no. 1 and 3; Chemosis: No swelling (Normal) was observed in animal no. 1 and 3.

The individual mean score for animal nos. 1, 2 and 3 at 24, 48, 72 hours for corneal opacity, iris, conjunctiva and chemosis were found 0.00, 0.00, 2.00, 1.00; 0.00, 0.00, 1.33, 1.00, and 0.00, 0.00, 2.00, 1.00, respectively.

Under the experimental conditions tested, all the three animals were fully reversible within an observation period of 14 for animal no. 2. and 21 days for animal no. 1 and 3. Hence, under the experimental test conditions, 1-phenylethanol [CAS: 98-85-1] was considered to be an eye irritant. It was further classified under the category "Category 2".

This is supported by another study performed in rabbits to assess the irritation potency of 1 -Phenylethanol.

Normal albino rabbit eyes were selected on the basis of absence of grossly visible staining by a 5-percent aqueous solution of fluorescein sodium, flushed with distilled water 20 seconds after application. A 2 hour interval was given so that the eye could return back to normal condition. Then, 0.005 ml of the undiluted test material was applied to the center of the cornea while the lids were retracted. About one minute later, the lids were released. This procedure is necessary to prevent the removal of a portion of the dose by the very efficient wiping system of the lids before intimate contact has been made with the eye. 18 to 24 hours later, the eyes were examined in strong diffuse daylight, then stained with fluorescein, and the injury was scored.

1-Phenylethanol was a Grade 7 eye hazard, defined by necrosis on over 63% of the cornea 24 h after exposure to 0.005 ml of a 40% solution in PEG but less than 63% necrosis from a 15% solution.

Hence, 1-Phenylethanol can be considered to be irritating to rabbit eyes.

The results from the above studies indicate a strong possibility of 1-phenylethanol being irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, 1-phenylethanol can be classified under the category “Category 2”.

Justification for classification or non-classification

Available studies for 1-phenylethanol indicate that it is not likely to cause any irritation to skin.

Hence, 1-phenylethanol can be considered to be not irritating to skin. It can be further classified under the category "Not Classified" as per CLP Regulation.

The results of the experimental studies target chemical indicate a possibility that1-phenylethanol can cause irritation to eyes.

Hence,1-phenylethanol can be considered to be irritating to eyes. It can be further classified under the category "Category 2" as per CLP regulation.