Registration Dossier

Administrative data

Description of key information

Skin irritation:
The substance did not give indications for skin irritating properties when applied to rabbits' skin.
Eye irritation:
The substance was considered to be non-irritating to rabbits' eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1985-04-11 to 1985-04-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to GLP and OECD Guideline. For justification of read across see section 13.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.24-2.66 kg
- Housing: single
- Diet: ad libitum, Rabbit Diet (A.W. Tindall Limited, Holbeach, Lincolnshire)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20+/-1.0°C
- Humidity (%): 51-55
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:
4 h
Observation period:
examination of the test site at 1, 24, 48 and 72 hours after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: back
- Type of wrap if used: The trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing: swabbing with cotton wool soaked in ether
- Time after start of exposure: 4 hours (after removal of the patch)

SCORING SYSTEM: after Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: (24 h /48 h/ 72 h)
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: (24 h /48 h/ 72 h)
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: (24 h /48 h/ 72 h)
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 h / 48 h / 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 h / 48 h / 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24 h / 48 h / 72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
The test material produced no evidence of primary cutaneous irritation in any rabbit throughout the 72 hours observation period. Desquamation extending beyond the site of application was observed in all three rabbits at the 72 hours reading only.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced no evidence of primary cutaneous irritation in any rabbit throughout the 72 hours observation period. The test material produced mean erythema and edema scores of 0 for all tested animals calculated over the time points 24, 48, 72 h and was classified as non-irritant to the skin.
Executive summary:

The test material was applied to the clipped back of three New Zealand White rabbits. Therefore, 0.5 mL were applied under a semiocclussive dressing and fixed for a duration of 48 hours. Afterwards, the patches were removed and the test sites were examined at 1, 24, 48 and 72 hours after removal to score the reactions. The test material produced no evidence of primary cutaneous irritation in any rabbit throughout the 72 hours observation period. Desquamation extending beyond the site of application was observed in all three rabbits at the 72 hours reading only. The test material produced mean erythema and edema scores of 0 for all tested animals calculated oer the time points 24, 48, 72 h and was classified as non-irritant to the skin.

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1985-04-15 to 1985-04-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to GLP and OECD Guideline. For justification of read across see section 13.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire
- Age at study initiation: app roximately 12 to 16 weeks
- Weight at study initiation: weight range 2.63 - 3.16 kg
- Housing: indicidually
- Diet: standard laboratory diet (Rabbit Diet, A.W. Tindall Limited, Holbeach, Lincolnshire), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/- 2 °C
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
Single treatment, eyelids were held together for about 1 second
Observation period (in vivo):
7 days, assessment of damage/irritation was made 1, 24, 48 and 72 hours following treatment.
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:
according to Draize J.H., 1959, Association of Food and Drug Officials of USA, Austin, Texas "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics").


TOOL USED TO ASSESS SCORE: standard ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 h / 48 h 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 h / 48 h 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24 h / 48 h 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 h / 48 h 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24 h / 48 h 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24 h / 48 h 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 h / 48 h 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24 h / 48 h 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24 h / 48 h 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 h / 48 h 72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24 h / 48 h 72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24 h / 48 h 72 h
Score:
0
Max. score:
4
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A test was conducted on methyl benzoate to assess its eye irritating potential to rabbits' eyes. Three rabbits were used. As a result, the substance was considered to be non irritating to eyes.
Executive summary:

A test was conducted on methyl benzoate to assess its eye irritating potential to rabbits' eyes. Three New Zealand White rabbits were used. The study was performed in accordance to GLP and OECD Guideline 405. After a single application of 0.1 mL methyl benzoate, the animals were observed for a period of 7 days and eye reactions were recorded at 1, 24, 48 and 71 hours. The mean scores for cornea opacity calculated for the time points 24, 48 and 72 hours were 0, 0, 0 for animal1, 2 and 3, respectively. Iris mean scores were 0, 0, 0 as well. The conjunctiva scores were calculated to be 0.67, 0.67, 0.67 and chemosis scores were 0.67, 0.67 and 0. All findings were reversible within 72 hours. On the basis of these results, the substance is considered to be non irritating to the rabbits' eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a read across study methyl benzoate was applied to the clipped back of three New Zealand White rabbits. 0.5 mL test material were applied under a semiocclussive dressing and fixed for a duration of 48 hours. Afterwards, the patches were removed and the test sites were examined at 1, 24, 48 and 72 hours after removal to score the reactions. The test material produced no evidence of primary cutaneous irritation in any rabbit throughout the 72 hours observation period. Desquamation extending beyond the site of application was observed in all three rabbits at the 72 hours reading only. The test material produced mean edema scores of 0 for all of the three animals, calculated over the time points 24, 48 and 72 hours and mean erythema scores of 0 for all animals as well. Therefore the test substance was considered to be non-irritating to the skin.

A publication is also available which includes a summary of toxicity test results including skin irritation results. Among several other substances, ethyl benzoate was tested. The skin irritation study was conducted on 5 albino rabbits. 0.01 mL of the substance (diluted or undiluted) was applied to the clipped skin. Assessment of the skin reactions was performed on the basis of a 10-grade scoring system, according to which the severest reaction found was evaluated. Ethyl benzoate was scored 4 in this test.

In another study (see chapter 7.10.3) ethyl benzoate was applied to the back skin of 5 volunteers. The substance was applied on a patch, the test duration was 48 hours (under occlusion). Afterwards, no signs of irritation were found on the skin. On the basis of these results the substance was considered to be non-irritating to the skin.

Furthermore, a skin irritation study on rabbits is described. Ethyl benzoate was applied to clipped back skin (0.5 mL) and also on outer ear skin (0.2 mL) of 10 New Zealand White rabbits. The test sites were not occluded. Application was repeated daily for a maximum of 6 days. 4 hours and 24 hours after application the test sites were examined macroscopically. 2 of the animals were killed each day to perform histopathological examinations of the treated skin sites. Macroscopical lesions (erythema and oedema) were only found on the back skin (increasing in severity with increasing number of applications) but not on the ear skin. Histological lesions were found both on back and outer ear skin. As the method of evaluation is not specified in this publication, it was evaluated as disregarded study.

Eye irritation

A test was conducted on methyl benzoate to assess its eye irritating potential to rabbits' eyes. Three New Zealand White rabbits were used. The study was performed in accordance to GLP and OECD Guideline 405. After a single application of 0.1 mL methyl benzoate, the animals were observed for a period of 7 days and eye reactions were recorded at 1, 24, 48 and 72 hours. The mean scores for cornea opacity calculated for the time points 24, 48 and 72 hours were 0, 0, 0 for animal 1, 2 and 3, respectively. Iris mean scores were 0, 0, 0 as well. The conjunctiva scores were calculated to be 0.67, 0.67, 0.67 and chemosis scores were 0.67, 0.67 and 0. All findings were reversible within 72 hours. On the basis of these results, the substance is considered to be non-irritating to the rabbits' eyes.

In another eye irritation study the test substance was administered to the eyes of five rabbits. Evaluation of the reactions was conducted on the basis of a 10 graded scale. The reactions were scored 1, which indicates a very small lesion that results from 0.5 mL of the undiluted chemical in the eye. As this scoring system is a non-standard system, interpretation of these results is not possible.


Justification for selection of skin irritation / corrosion endpoint:
most reliable study available

Justification for selection of eye irritation endpoint:
most reliable study available

Justification for classification or non-classification

The available data gave no indications for a skin or eye-irritating property of the test substance. On the basis of these data the substance is not considered to be classified for skin or eye irritation under Directive 67/548/EEC (DSD) or under Regulation (EC) No 1272/2008 (CLP).