Registration Dossier
Registration Dossier
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EC number: 204-262-9 | CAS number: 118-58-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Endpoint summary
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
- 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.
- 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.
Referenceopen allclose all
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.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- 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. - 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.
Referenceopen allclose all
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 |
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).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
