Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Not corrosive to skin. Not a skin irritant.
Not corrosive to eyes, however, it is an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1985-04-16 to 1985-04-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A Smith, 7 Kydcomb Road, Warlingham, Surrey, United Kingdom.
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: Individually in anodised aluminium cages with grid floors and no bedding materials.
- Diet: Ad libitum, commercial pelleted rabbit diet (680, Dalgety-Spillers Ltd)
- Water: Mains tap water (presumably ad libitum)
- Acclimation period: ≥ 5 d.

ENVIRONMENTAL CONDITIONS
- Temperature: 18 °C - 22 °C
- Humidity: 42 % - 65 %
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.5 mL
Duration of treatment / exposure:
4 hrs
Observation period:
7 d (observations at 1 hr, 24 hrs, 48 hrs, 72 hrs, 7 d after removal of patch)
Number of animals:
4 female
Irritation parameter:
erythema score
Basis:
animal: 552
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal: 552
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
erythema score
Basis:
animal: 554
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal: 554
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal: 556
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
animal: 556
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal: 557
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
edema score
Basis:
animal: 557
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Remarks:
48 hr
Irritant / corrosive response data:
Based on the mean scores (24, 48 and 72-hour observations) of each of the four rabbits, the overall mean score per observed reaction is:
Oedema: 0.2
Erythema: 0.6
Other effects:
None noted.

The numerical values or scores given to the erythema observed in each animal of the treated group at the 24, 48 and 72- hour examinations were summed. This total was then divided by three, the number of examinations that the figures were taken from, and further divided by the number of animals in the group. The values obtained in assessing oedematous reaction were similarly treated. The average scores obtained may be used in any subsequent classification of the material, a value of 2 or more for either erythema or oedema resulting in the material being regarded as irritant.

The maximum score recorded in the table above represents the maximum score attainable and not the maximum observed score in any single animal.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Following the application of ca. 0.5mL of neat test substance to the shorn flanks of 3 rabbits for 4 hours very slight erythema and oedema were observed up to 72 hours after dosing. All reactions were reversible 7 days after dosing.
Executive summary:

Approximately 0.5mL of neat test substance was applied to the shorn flanks of three rabbits, wrapped in semi-occlusive dressing for a period of four hours. One hour after the dosing period well defined erythema of the treated skin was apparent in one rabbit and very slight erythema was observed in the remaining three rabbits of the group. Slight oedema was noted in one rabbit and very slight oedematous reaction was observed in the treated skin of the second rabbit at this time. Very slight erythema remained in three rabbits at twenty four hour observation, very slight oedema also being observed in two rabbits. This response declined, very slight erythema remaining in two animals 72 hours after dosing and no irritation remaining visible 7 days after dosing. The averages calculated from the numerical values given to the irritation observed at the 24, 48 and 72 -hour observations were 0.6 for erythema and 0.2 for oedema.

The effects seen do not trigger classification according to Regulation (EC) No. 1272/2008 (CLP).

Endpoint:
skin irritation: in vivo
Remarks:
no data
Type of information:
other: Published literature
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Published literature containing summary of investigation into irritation effects of similar substances.
Qualifier:
no guideline followed
Principles of method if other than guideline:
A report summarizing the scientific data relevant to risk assessment of salicylates as fragrance ingredients.
GLP compliance:
not specified
Species:
other: Humans, rabbits and guinea pigs
Strain:
other: Himalayan white-spotted guinea pigs, Hartley albino guinea pigs and New Zealand white rabbits
Type of coverage:
other: Open, semi-occlusive and occlusive
Preparation of test site:
not specified
Vehicle:
other: See amount/concentration applied.
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
Human Studies
Maximisation pre-test (48 h occluded patch): 30 % in petrolatum
Maximisation pre-test (48 h occluded patch): 30 % in petrolatum
HPIRT pre-test (48 h occluded patch): 5 % in dimethyl phthalate
HPIRT induction phase (24 h occluded patch): 10 % in alcohol
HPIRT induction phase (24 h occluded patch): 15 % in 3:1 DEP:ethanol
48 h occluded patch: 0 % in vaselium aldum
24 - 27 h occluded patch: 2 % in unguentum simplex
24 h occluded patch: 5 % in vaseline
4 h occluded patch: 100 % (0.2 mL aliquot)

Animal Studies
Pre-test for an OET (24 h open application): 0.03 - 100 % as a single application (vehicle not specified).
Induction phase of an OET: 0.03 - 100 % as a single application (vehicle not specified).
Pre-test for Draize (open application): 2 % vehicle not specified
Primary skin irritation study (4 h semi-occlusive): 100 %
Pre-test for sensitisation assay (24 h closed patch test): 10 % in SDA 39 C alcohol
Irritation evaluated during an associated LD50 study: 100 %
Irritation studies as part of a phototoxicity study (open, 24- and 48-h assay): 5 %, 10 % and 30 % in acetone
Irritation studies as part of a phototoxicity study (occlusive, 1.5-h assay): 5 % and 10 % in alcohol
Duration of treatment / exposure:
Human Studies
Maximisation pre-test (48 h occluded patch): 48 h
Maximisation pre-test (48 h occluded patch): 48 h
HPIRT pre-test (48 h occluded patch): 48 h
HPIRT induction phase (24 h occluded patch): 24 h
HPIRT induction phase (24 h occluded patch): 24 h
48 h occluded patch: 48 h
24 - 27 h occluded patch: 24 - 27 h
24 h occluded patch: 24 h
4 h occluded patch: 4 h

Animal Studies
Pre-test for an OET (24 h open application): 24 h
Induction phase of an OET: 21 days
Pre-test for Draize (open application): No data
Primary skin irritation study (4 h semi-occlusive): 4 h
Pre-test for sensitisation assay (24 h closed patch test): 24 h
Irritation evaluated during an associated LD50 study: No data
Irritation studies as part of a phototoxicity study (open, 24- and 48-h assay): 24- and 48-h
Irritation studies as part of a phototoxicity study (occlusive, 1.5-h assay): 1.5-h
Observation period:
No data
Number of animals:
Human Studies
Maximisation pre-test (48 h occluded patch): 5 volunteers
Maximisation pre-test (48 h occluded patch): 22 volunteers
HPIRT pre-test (48 h occluded patch): 8 volunteers
HPIRT induction phase (24 h occluded patch): 35 volunteers
HPIRT induction phase (24 h occluded patch): 101 volunteers
48 h occluded patch: 5 volunteers
24 - 27 h occluded patch: 30 volunteers
24 h occluded patch: 25 volunteers
4 h occluded patch: 30 volunteers

Animal Studies
Pre-test for an OET (24 h open application): 6-8/sex/group (Himalyan white spotted guinea pigs)
Induction phase of an OET: 6-8/sex/group (Himalyan white spotted guinea pigs)
Pre-test for Draize (open application): 4 Hartley albino guinea pigs, sex not specified
Primary skin irritation study (4 h semi-occlusive): 4 females (New Zealand white rabbits)
Pre-test for sensitisation assay (24 h closed patch test): 3 albino rabbits, sex not specified
Irritation evaluated during an associated LD50 study: 3 rabbits, sex not specified
Irritation studies as part of a phototoxicity study (open, 24- and 48-h assay): 5 females
Irritation studies as part of a phototoxicity study (occlusive, 1.5-h assay): 2/sex/group (guinea pigs)
Irritation parameter:
overall irritation score
Remarks on result:
no indication of irritation
Conclusions:
A number of studies conducted on both human volunteers and animals were reviewed. Approximately 958 male and female human volunteers were tested in standard 24 h or 48 h closed patch tests on various salicylates. A questionable reaction was observed when the target substance was assessed in 30 % petrolatum in a 48 h closed patch test, with 2/22 volunteers having a questionable response. The volunteers in other studies were negative, with no further reactions.
In addition to the large number of human studies, a series of animal studies conducted on rabbits and guinea pigs were also reviewed. The animal tests included pre-tests conducted prior to or as part of skin sensitisation assays, including open epicutaneous tests, Draize tests or as part of phototoxicity or photoallergy studies. The target substance produced no irritation reactions with concentrations up to 0.03 % in guinea pigs. The target substance showed no irritation when tested at 100 % in rabbits.
It may be concluded therefore that the target substance is not classified as a skin irritant.
Executive summary:

A review of several salicylates used as fragrance ingredients concluded that Benzyl salicylate is not a skin irritant in rabbits. As part of a weight of evidence, it may be concluded that the registration is not classified as a skin irritant.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older GLP study.
Qualifier:
equivalent or similar to guideline
Guideline:
other: Annex V test methods EEC Directive 79/831.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised breeders whose standards are acceptable to the animal welfare department of the testing facilities.
- Age at study initiation:
- Weight at study initiation:
- Housing: Individually in anodised wire mesh cages with no bedding.
- Diet: Ad libitum SQC standard rabbit diet (Special Diet Services Ltd, Witham, Essex, United Kingdom)
- Water: Ad libitum mains water
- Acclimation period: ≥ 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 18 °C to 23 °C
- Humidity: 40 % to 80 %:
- Air changes (per hr): No data
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.5 mL
Duration of treatment / exposure:
4 hrs
Observation period:
7 d (observations at 1 hr, 24 hrs, 48 hrs, 72 hrs, 7 d after removal of patch)
Number of animals:
3 females (each animal tested with multiple substances)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm²
- Type of wrap if used: Elastoplast elastic adhesive barrier, 10 cm width.

REMOVAL OF TEST SUBSTANCE
- Washing: Adhesive tapes removed, gentle swabbing with cotton wool soaked in warm water
- Time after start of exposure: 4 hrs

SCORING SYSTEM:
- Erythema and eschar formation:
-- 0: No erythema
-- 1: Very slighty erythema (barely perceptible)
-- 2: Well-defined erythema
-- 3: Moderate to severe erythema
-- 4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)
- Oedema formation:
-- 0: No oedema
-- 1: Very slight oedema (barely perceptible)
-- 2: Slight oedema (edges of area well defined by definite raising)
-- 3: Moderate oedema (raised approximately 1 mm)
-- 4: Severe oedema (raised more than 1 mm and extending beyond area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
190
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 hr
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
201
Time point:
24/48/72 h
Score:
0.667
Max. score:
2
Reversibility:
fully reversible within: 72 hr
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
203
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
190
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hr
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
201
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 hr
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
203
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
No other abnormalities detected.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Following exposure to ca. 0.5 g of substance in contact with skin for four hours the substance is considered not to be a skin irritant to rabbits.
Executive summary:

Administration of ca. 0.5g of neat substance to the shorn flanks of three rabbits and wrapped in semi-occlusive tape for 4 hours resulted in well defined erythema and slight oedema after one hour observation at the treated site of one rabbit. Well defined erythema and very slight oedema was apparent at the treated skin site of a second rabbit and the treated skin of the remaining rabbit exhibited very slight erythema. Very slight erythema remained at the treated sites of two rabbits twenty four hours after dosing, the reaction declining in one rabbit by the forty-eight hour observation. No other irritant response was apparent after this time and all effects were reversible at the 72 -hour observation.

Under the conditions of the test, the substance is not considered to be a skin irritant.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed on 04 February 2012.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: Excised Bovine Cornea
Strain:
other: Not Applicable
Details on test animals or tissues and environmental conditions:
Not applicable
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL

-Amounts(s) applied (volume or weight with unit):
0.75 mL of the test material was applied to triplicate corneas.

-Concentration (if solution):
The test material was used as supplied.

VEHICLE
No vehicle used
Duration of treatment / exposure:
The undiluted test material was applied for 10 minutes followed by an incubation period of 120 minutes.
Observation period (in vivo):
Not applicable
Number of animals or in vitro replicates:
Not applicable
Details on study design:
TEST SITE
-Area of exposure
0.75 mL of the test material was applied to triplicate corneas.

-% coverage:
The test material was topically applied to the cornea. The holders were gently tilted back and forth to ensure a uniform application of the material over the entire cornea.

-Type of wrap used:
None used

REMOVAL OF TEST SUBSTANCE
-Washing (if done):
At the end of the exposure period the test material was removed from the anterior chamber and each cornea was rinsed three times with fresh complete MEM containing phenol red before a final rinse with complete MEM.

-Time after start of exposure:
10 minutes post exposure

SCORING SYSTEM:
Results from the two test method endpoints, opacity and permeability, were combined in an empirically derived formula to generate an In Vitro Irritancy Score.
Opacity Measurement-
The change in opacity for each cornea (including the negative control) was calculated by subtracting the initial opacity reading from the final opacity reading. These values were then corrected by subtracting from each the average change in opacity observed for the negative control corneas. The mean opacity value of each treatment group was then calculated by averaging the corrected opacity values of each cornea for that treatment group.

Permeability Measurement
The corrected OD492 was calculated by subtracting the mean OD492 of the negative control corneas from the OD492 value of each treated cornea. The OD492 value of each treatment group was calculated by averaging the corrected OD492 values of the treated corneas for the treatment group.

The following formula was used to determine the in vitro score:
In Vitro Irritancy Score = mean opacity value + (15 x mean OD492 value)

DATA INTERPRETATION
A test material that induces an in vitro irritancy score > than or equal to 55.1 is defined as an ocular corrosive or severe irritant.

Additionally, the opacity and permeability values were evaluated independently to determine whether the test material induced a response through only one of the two endpoints.

Visual Observation
The condition of the cornea was visually assessed immediately after rinsing and at the final opacity measurement.
Irritation parameter:
cornea opacity score
Run / experiment:
mean value
Value:
0
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
The test material induced an in vitro irritancy score of 0.0
The corneas treated with the test item were clear post treatment and post incubation.

RESULTS

Corneal Opacity and Permeability Measurement

Individual and mean corneal opacity measurements and individual and mean corneal permeability measurements are given in Table 1.

Corneal Epithelium Condition

The condition of the cornea immediately after rinsing and at the final opacity measurement is given in Table 2.

In Vitro Irritancy Score

The results are summarised as follows:

Treatment

In Vitro Irritancy Score

Test Material

0.0

Negative Control

3.8

Positive Control

31.2

Criteria for an Acceptable Test

The positive control In Vitro irritancy Score was within the range of 30.9 to 67.7. The positive control acceptance criterion was therefore satisfied.

Table 1          Individual and Mean Corneal Opacity and Permeability Measurements

Treatment

Cornea Number

Opacity

Permeability (OD)

In vitroIrritancy Score

Pre-Treatment

Post-Treatment

Post-Incubation

Post-Incubation-Pre‑Treatment

Corrected Value

 

Corrected Value

Negative Control

1

3

3

6

3

 

0.036

 

 

2

2

2

5

3

 

0.031

 

 

3

2

2

6

4

 

0.025

 

 

 

 

 

 

3.3*

 

0.031¨

 

3.8

Positive Control

4

3

26

27

24

20.7

0.698

0.667

 

5

2

27

27

25

21.7

0.614

0.583

 

6

4

31

31

27

23.7

0.610

0.579

 

 

 

 

 

 

22.0·

 

0.610·

31.2

Test Item

10

2

3

3

1

0.0

0.033

0.002

 

11

3

3

4

1

0.0

0.015

0.000

 

12

3

3

3

0

0.0

0.015

0.000

 

 

 

 

 

 

0.0·

 

0.001·

0.0

OD= Optical density      * = Mean of the post treatment-pre‑treatment values    ¨= Mean permeability      ·= Mean corrected value


Table 2          Corneal Epithelium Condition

Treatment

Cornea Number

Observation

Post Treatment

Post Incubation

Negative Control

1

clear

clear

2

clear

clear

3

clear

clear

Positive Control

4

cloudy

cloudy

5

cloudy

cloudy

6

cloudy

cloudy

Test Item

10

clear

clear

11

clear

clear

12

clear

clear

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
The test item was considered not to be an ocular corrosive or severe irritant, in vitro.
Executive summary:

Introduction. 

A study was performed to assess the ocular irritancy potential of the test item to the isolated bovine cornea. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 437 (2009) “Bovine Corneal Opacity and Permeability Assay”

Method. 

The undiluted test item was applied for 10 minutes followed by an incubation period of 120 minutes. Negative and positive control items were tested concurrently. The two endpoints, decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability) were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS). 

Results. 

The in vitro Irritancy scores are summarised as follows:

Treatment

In Vitro Irritancy Score

Test Item

0.0

Negative Control

3.8

Positive Control

31.2

Conclusion. 

The test item was considered not to be an ocular corrosive or severe irritant.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted in accordance with good scientific principles and the data reported was sufficient to classify the substance as an eye irritant. In the interest of animal welfare it was considered unecessary to repeat the study.
Qualifier:
according to guideline
Guideline:
other: Draize "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", Association of Food and Drug Officials of the United States
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Before the guideline was adopted.
Principles of method if other than guideline:
Three normal, healthy, albino rabbits were used in this study. Each animal had 0.1mL of the test sample instilled into the right eye with no further treatment. The untreated left eye of each animal served as its own control.
Both the treated and control eye were examined every 24-hours for 4 days and then again on the seventh day. The scores recorded were made according to the Draize scale for scoring occular lesions.
GLP compliance:
no
Remarks:
study predates GLP
Species:
rabbit
Strain:
other: Albino
Vehicle:
other: Alcohol SDA 39C
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.1 mL
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
10 d
Number of animals or in vitro replicates:
3
Details on study design:
NON-REMOVAL OF TEST SUBSTANCE
- Washing: None

SCORING SYSTEM:
- Draize system (please refer to attached supporting information).

TOOL USED TO ASSESS SCORE:
- Fluorescein
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 3 days
Other effects:
No other scores reported.
The maximum score quoted above represents the maximum possible score based on the scoring system used (Draize).

Interpretation of results:
irritating
Remarks:
Migrated information Category 2 eye irritant in accordance with CLP. Criteria used for interpretation of results: EU
Conclusions:
The substance is classified as an eye irritant.
Executive summary:

Approximately 0.5mL of the test substances was instilled into the eyes of three albino rabbits. 1, 2, 3, 4, 7 and 10 days after exposure reactions were recorded.

The effects on the conjunctivae (redness) were sufficient in 2 out of 3 animals tested to trigger classification as category 2 eye irritation in accordance with Regulation (EC) 1272/2008 (CLP).

All advsere reactions were reversed within 7 days.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Following exposure to Benzyl Salicylate (Target Substance) and the Source Substance, Cyclohexyl Salicylate, via contact with skin the substance is considered not to be a skin irritant to rabbits.

Eye irritation:

An in vitro (BCOP) study on the substance, Benzyl salicylate, indicates that the substance is not corrosive to eyes or a severe eye irritant.

In the in vivo study, Benzyl Salicylate is considered to be an irritant to the eyes of rabbits. Irritation (redness) in 2 out of 3 animals is sufficient to classify the substance in accordance with CLP. According to guidance, as the effects observed are fully reversible within 7 days (3 days for Benzyl Salicylate), the substance is considered to be mildly irritating to eyes (category 2B).

For classification and labelling purposes this indicates that the structural analogue is relatively harmless and would not, in itself, be classified in accordance with Regulation (EC) No 1272/2008 (CLP). The registration substance is considered to have similar properties and is therefore not classified in accordance with CLP.


Justification for selection of skin irritation / corrosion endpoint:
Following exposure to Benzyl Salicylate (Target Substance) and the Source Substance, Cyclohexyl Salicylate, via contact with skin the substance is considered not to be a skin irritant to rabbits.

Justification for selection of eye irritation endpoint:
Benzyl Salicylate (Target Substance) was considered not to be an ocular corrosive or severe irritant, in vitro (BCOP) in a K1 rated GLP/ OECD test guideline study.
Benzyl Salicylate is considered, however, to be an irritant to the eyes of rabbits. Irritation (redness) in 2 out of 3 animals is sufficient to classify the substance in accordance with CLP (category 2B).

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Following exposure to Benzyl Salicylate via contact with skin the substance is considered not to be a skin irritant to rabbits, therefore not classified in accordance with CLP.

Benzyl Salicylate was considered not to be an ocular corrosive or severe irritant, in vitro (BCOP) in a K1 rated GLP/ OECD test guideline study.
Benzyl Salicylate is considered, however, to be an irritant to the eyes of rabbits. Irritation (redness) in 2 out of 3 animals is sufficient to classify the substance in accordance with CLP (category 2B).