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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from experimental report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
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 “Benzyl propionate (CAS No. - 122-63-4)” on eye, when exposed by the ocular route in rabbits.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report):Benzyl propionate
- Molecular formula : C10H12O2
- Molecular weight : 164.20 g/mol
- Substance type:Organic
- Physical state:Colourless Liquid
- AI Content:99.39 %
- Lot/batch No.:Lot 1/04
- Storage condition of test material:Tightly closed, in well-ventilated place. Keep away from source of ignition - no smoking.
- Other:
Handling and Disposal
Safety precautions : Take precautionary measures against static discharges. Kept away from source of ignition. When using do not eat or drink, Aprons, caps, mask, 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 of sa-FORD.
Specific details on test material used for the study:
Name of test material (as cited in study report):Benzyl propionate
- Molecular formula : C10H12O2
- Molecular weight : 164.20 g/mol
- Substance type:Organic
- Physical state:Colourless Liquid
- AI Content:99.39 %
- Lot/batch No.:Lot 1/04
- Storage condition of test material:Tightly closed, in well-ventilated place. Keep away from source of ignition - no smoking.
- Other:
Handling and Disposal
Safety precautions : Take precautionary measures against static discharges. Kept away from source of ignition. When using do not eat or drink, Aprons, caps, mask, gloves and goggles were used to ensure

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:Procured from RABBI ROOF Animal Facility, A. P., India.
- Age at study initiation:4.5 to 5 Months (Approximately)
- Weight at study initiation:Minimum: 1.924 kg and Maximum: 2.038 kg (Prior to Treatment)
- Health Status :Healthy young adult.
- 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, Pune) 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: 19.50 °C and Maximum: 22.20 °C
- Humidity (%):Minimum: 41.20 % and Maximum: 59.20 %
- 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):
Animals were observed at 24 hours intervals for 72 hours.
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:N/A

TOOL USED TO ASSESS SCORE: Ophthalmoscope and fluorescent strips.

Results and discussion

Results of in vivo studyopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1,#2 and #3
Time point:
other: 24,48 and 72 hrs
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: Untreated (Control Eye)
Irritation parameter:
iris score
Basis:
animal: #1,#2 and #3
Time point:
other: 24,48 and 72 hrs
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: Untreated (Control Eye)
Irritation parameter:
conjunctivae score
Basis:
animal: #1,#2 and #3
Time point:
other: 24,48 and 72 hrs
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: Untreated (Control Eye)
Irritation parameter:
chemosis score
Basis:
animal: #1,#2 and #3
Time point:
other: 24,48 and 72 hrs
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: Untreated (Control Eye)
Irritation parameter:
cornea opacity score
Basis:
animal: #1,#2 and #3
Time point:
other: After 24, 48, 72 Hours
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: For treated eye
Irritation parameter:
iris score
Basis:
animal: #1,#2 and #3
Time point:
other: After 24, 48, 72 Hours
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: For treated eye
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: After 24 Hours
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: For treated eyes
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: After 48 Hours
Score:
0.67
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: For treated eyes
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: After 72 Hours
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: For treated eyes
Irritation parameter:
chemosis score
Basis:
animal: #1,#2 and #3
Time point:
other: After 24, 48, 72 Hours
Score:
0
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: 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 3 animals; Area of Opacity- Zero in all the animals; Iris: Normal in all the animals. Conjunctivae - Some blood vessels definitely hyperaemic (injected) in all the animals; Chemosis: Some swelling above normal (includes nictating membranes) were observed in animal number 1 and 3 whereas animal number 2 was normal.
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 animal no. 2. Animal no. 1 and 3 recovered to normal; Chemosis: No swelling 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 Animal Nos 1, 2 and 3, respectively.
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 - Some blood vessels definitely hyperaemic (injected) was observed in animal no. 3 at 48 hours which was recovered to normal at 72 hours observation whereas blood vessels were normal in Animal Numbers 1 and 3 at 48 and 72 hours observation; Chemosis: No swelling was observed in all the animals.
The individual mean score for Animal Nos. 1, 2 and 3 at 24, 48, 72 hours for Corneal opacity, iris, conjunctiva, chemosis were found 0.00, 0.00, 0.00, 0.00 ; 0.00, 0.00, 0.67, 0.00 and 0.00, 0.00, 0.00, 0.00, 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 were weighed on test day 0 (prior to application) and at termination.
The body weights were marginally increased in all the animals when compared with pre-treatment body weight.

Any other information on results incl. tables

Table 1 : Individual Animal Eye Irritation Scores

 

In Treated area Dose:0.1 ml of 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

0

0

0

0

1

1

1

0

0

1

0

0

0

Chemosis

0

1

0

0

0

0

0

0

0

0

0

1

0

0

0

Corneal Damage%

0

0

0

 

 

 

Dose:Untreated (Control Eye)                                                                       Sex:Male

Animal Numbers

1

2

3

Application Side

Left

Left

Left

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

1

0

0

0

Corneal Damage%

0

0

0

Key:*= Pre-exposure eye examination,h = Hour.

 

Table 1 Continued…

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

0.00

0.67

0.00

Chemosis

0.00

0.00

0.00

 

 

Formula :

 

Mean Eye Irritation Score =

Sum of the Individual Animal Score for eye reactionat24, 48 and 72 hours

Number of the Observations (3)

 

                          

 

Table 2 : Individual Animal Clinical Signs

 

Sex:Male

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

Sex :Male

Animal No.

Animal Body Weight (kg)

Prior to application

At termination

1

1.950

1.978

2

2.038

2.128

3

1.924

1.962

Key:kg = Kilogram

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Conclusions:
Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of rabbits was observed at 72 hours.
Hence under the experimental test conditions, Benzyl propionate (CAS No. - 122-63-4) is “Non Irritant” to New Zealand White Male rabbit eyes and is being classified as “Not classified” as per the CLP regulation.
Executive summary:

Acute Eye Irritation/Corrosion Study of Benzyl propionate (CAS no. - 122-63-4) in Rabbits, was performed in a OECD GLP laboratory (Sustainability Support Services (Europe) has letter of access).The study was performed according to OECD 405 Guidelines.

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 test itemwas applied into the conjunctival sac of the right eye of Animal No.1. The left eye of the rabbit served as the control. Animal No. 1 presented ocular lesions at 1 hour observation period. Hence the confirmatory test was conducted on additional two rabbits (Animal No. 2 and 3);0.1 ml of test itemwas instilled into the conjunctival sac of right eye and left eye served as the control. Ocular lesions were observed at 1, 24 and 48 hour in Animal Number 2 whereas in Animal Number 3 ocular lesions presented only at 1 hour observation period. Untreated eye of the treated 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 3 animals; Area of Opacity-Zero in all the animals;Iris:Normal in all the animals.Conjunctivae -Some blood vessels definitely hyperaemic (injected) in all the animals;Chemosis:Some swelling above normal (includes nictating membranes) were observed in animal number 1 and 3 whereas animal number 2 was normal. 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 animal no. 2. Animal no. 1 and 3 recovered to normal;Chemosis:No swelling 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 Animal Nos 1, 2 and 3, respectively. 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 -Some blood vessels definitely hyperaemic (injected) was observed in animal no. 3 at 48 hours which was recovered to normal at 72 hours observation whereas blood vessels were normal in Animal Numbers 1 and 3 at 48 and 72 hours observation;Chemosis:No swelling was observed in all the animals. The individual mean score for Animal Nos. 1, 2 and 3at 24, 48, 72 hoursfor Corneal opacity, iris, conjunctiva, chemosis were found 0.00, 0.00, 0.00, 0.00 ; 0.00, 0.00, 0.67, 0.00 and 0.00, 0.00, 0.00, 0.00, respectively.

Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of rabbits was observed at 72 hours. 

Hence under the experimental test conditions, Benzyl propionate (CAS: 122-63-4) is “Non Irritant” to New Zealand White Male rabbit eyes and is being classified as “Not Classified” as per the CLP regulation.