Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 439): irritating

Eye irritation (weight of evidence): irritating (including read-across)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21-01-2014 until 24-01-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
GLP compliance:
yes
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: SkinEthic Laboratories, Lyon, France
Source strain:
other: Not applicable
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: Skin Ethic RHE / S / 17
- Tissue batch number(s): 14 RHE 0101
- Production date: 20 January 2014
- Shipping date: 21 January 2014
- Delivery date: 21 January 2014
- Date of initiation of testing: 21 january 2014

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37°C
- Temperature of post-treatment incubation (if applicable): 37°C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 1 mL PBS, 25 times

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: SpectraMax M5 (Molecular Devices)
- Wavelength: 570 nm
- Filter / Filter bandwidth / Linear OD range of spectrophotometer: No data

NUMBER OF REPLICATE TISSUES: Test was performed in triplicate

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritant to skin if the mean tissue viability after exposure is less than or equal to 50%.
- The test substance is considered to be non-irritant to skin if the mean tissue viability after exposure is more than 50%.

ACCEPTABIILITY CRITERIA
- The absolute absorbance at 570 nm of the negative control tissues in the MTT test is an indicator of tissue viability after the shipping and storing procedure and under specific conditions of the assay. Tissue viability is acceptable if the mean absorbance of the three negative controls is ≥ 1.2 and ≤2.5
- An assay is meeting the acceptance criterion if the mean relative tissue viability of the positive control is < 40%.
- The standard deviations (calculated from individual precental tissue viabilities) among tissues of the same treatment group should be ≤18%.

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: Cell viability at day 17 is 1.475 +/- 0.021 where an O.D. of > 0.7 is accepted
- Barrier function: Exposure time inducing 50% viability (using Triton X-100 1%) is 4.8h where 4-10h is accepted
- Morphology / contamination: The culture and histology of the skin is found to be conform (sufficient cell layers and good cell growth and sterility
- Reproducibility: The system is fully reproducible as it is commercially being sold by SkinEthic.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied: 16 µL

NEGATIVE CONTROL
- Amount(s) applied: 16µL

POSITIVE CONTROL
- Amount(s) applied: 16 µL
- Concentration: 5% in deionised water
Duration of treatment / exposure:
42 minutes
Duration of post-treatment incubation (if applicable):
42 ± 1 hours
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean
Value:
9.1
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: not reported
- Direct-MTT reduction: no

DEMONSTRATION OF TECHNICAL PROFICIENCY: No data

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes

Summary of results

Dose group

Absorbance 570 nm

Mean Absorbance of 3 tissues**

Relative viability [%] Tissue 1, 2, 3**

Relative viability [% of negative control]**

Standard deviation [%]**

Tissue 1*

Tissue 2*

Tissue 3*

Negative control (PBS)

2.091

2.178

2.127

2.132

98.1

100.0

2.0

102.2

99.8

Positive control (5% w/v SDS)

0.013

0.016

0.015

0.015

0.6

0.7

0.1

0.7

0.7

Test substance

0.237

0.152

0.190

0.193

11.1

9.1

2.0

7.2

8.9

*Mean of three replicate wells (per tissue) after blank correction

**Calculation based on exact means

Interpretation of results:
other: Category 2 (irritant)
Remarks:
based on CLP criteria
Conclusions:
Under the conditions of this test, the relative mean tissue viability for the test item determined to be 9.1%. This value is below the threshold for irritancy of ≤50%. Based on the results obtained, it can be concluded that Ethyllinalyl acetate is at least an irritant to skin and further research is needed to be able to assign a classification in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Executive summary:

The test substance was tested according to OECD 439 (non-GLP) with the in vitro reconstructed human epidermis model. 16µL test substance was applied and the tissues were exposed for 42 minutes at room temperature, in triplicate. After exposure the tissues were rinsed with PBS. After 42 hours post-incubation a MTT assay was performed to determine the cell viability. Negative and positive controls were run in parallel and acceptance criteria were met. Under the conditions of this test, the relative mean tissue viability for the test item determined to be 9.1%. This value is below the threshold for irritancy of ≤50%. Based on the results obtained, it can be concluded that Ethyllinalyl acetate is at least an irritant to skin and further research is needed to be able to assign a classification in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
See attached justification
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 15 days
Remarks on result:
other: Mean 1.0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
> 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 15d
Remarks on result:
other: Mean 0.6
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
>= 2 - <= 3
Max. score:
3
Reversibility:
fully reversible within: 15d
Remarks on result:
other: Mean 2.3
Irritation parameter:
chemosis score
Remarks:
Chemosis
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
2
Reversibility:
fully reversible within: 15d
Remarks on result:
other: Mean 0.4
Irritant / corrosive response data:
loss of corneal tissue (reversible)
Other effects:
pupil contraction, loss of hair at margins of eyelids, marginal vascularization of the cornea, small retractions in the eyelids

TABLE 1: EYE IRRITATION SCORES - INDIVIDUAL VALUES
Animal Number Sex Evaluation Interval* Corneal Opacity Area of Corneal Opacity Iris Conjunctivae Redness Chemosis Discharge
Symptoms
1 M 1 4 0 2 2 2 PC
2 M 1hour 0 0 0 2 2 3
3 F 0 0 0 2 2 3
1 M 1 4 0 2 1 1 PC
2 M 24 hours 1 2 0 2 0 1
3 F 1 2 1 3 1 1 PC
1 M 1 4 0 2 1 0 PC 
2 M 48 hours 1 4 0 2 0 0
3 F 1 3 1 3 0 1 PC/LC
1 M 1 3 1 2 1 2 PC/LC/RE
2 M 72 hours 1 3 1 2 0 0 PC/LC 
3 F 1 3 1 3 0 0 PC/LC
1 M 1 1 0 0 0 0 RE/MV/LH/LC
2 M 8 days 0 0 0 0 0 0
3 F 0 0 0 0 0 0
1 M 0 0 0 0 0 0 RE/LH
2 M 15 days 0 0 0 0 0 0
3 F 0 0 0 0 0 0
* Examinations were performed at the specified times after instillation of the test item.PC= pupils contracted, LC= loss of corneal tissue, LH= loss of hair at margins of eyelids, MV= marginal vascularization of the cornea, RE= small retractions in the eyelids
TABLE 2: EYE IRRITATION SCORES - MEAN VALUES AFTER 24, 48 AND 72 HOURS
Animal number Sex Corneal Opacity N Iris N Conjunctivae
Redness N Chemosis N
1 M 1.0 3 0.3 3 2.0 3 1.0 3
2 M 1.0 3 0.3 3 2.0 3 0.0 3
3 F 1.0 3 1.0 3 3.0 3 0.3 3
N = number of available data points.
Interpretation of results:
irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification (Commission Directive 2001/59/EC of August 06, 2001), Linalool is considered to be "not irritating" to the rabbit eye. Based upon the referred classification (Commission Regulation 1272/2008/EC of December 16, 2008), Linalool is considered to be "irritating" to the rabbit eye (Category 2). This result is used for read-across to ethyllinalyl acetate.
Executive summary:

The primary eye irritation potential of Linalool was investigated based on OECD test guideline no. 405. The test item was applied by instillation of 0.1 ml into the left eye of each of three young adult Vienna White rabbits. The treated eye was not washed and the untreated eye served as control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours and 8 and 15 d after test item installation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity were 1.00 for all three animals. The individual mean scores for Iris were 0.3, 0.3, 1.0, the conjunctivae were 2.0, 2.0 and 3.0 for reddening, respectively, and 1.0, 0.0 and 0.3 for chemosis. The instillation of Linalool into the eye resulted in pupil contraction, loss of hair at margins of eyelids, marginal vascularization of the cornea, loss of corneal tissue, and small retractions in the eyelids. These effects except retractions of eyelids and loss of hair at margins of eyelids were reversible and were no longer evident 15d after treatment, the end of the observation period for all animals. Retractions of eyelids and loss of hair are, however, expected to be reversible. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye. Based upon the standard classification criteria (Commission Directive 2001/59/EC of August 06, 2001), Linalool is considered to be "not irritating" to the rabbit eye. Based upon the referred classification (Commission Regulation (EC) 1272/2008 of December 16, 2008), Linalool is considered to be "irritating" to the rabbit eye (Category 2). This result is used for read-across to ethyllinalyl acetate.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
08.08.1988-26.09.1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study based on OECD guideline 405 (1981)
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
No data
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: SAVO. MED. VERSUCHSTIERZUCHTEN GMBH- Housing: THE ANIMALS WERE HOUSED I N FULLY AIR-CONDITIONED ROOMS. CENTRAL AIR-CONDITIONING GUARANTEED ARANGE OF 2 0 - 2 4 DEGREES CELSIUS FOR TEMPERATURE AND OF 3 0 - 70% FOR RELATIVE HUMIDITY.- Diet (e.g. ad libitum): 130 g per animal per day, Kliba 341, 4mm- Water (e.g. ad libitum): 250 ml per animal per day- Acclimation period: AT LEAST 8 DAYS BEFORE THE BEGINNING OF THE STUDV: SAME HOUSING CONDITIONS AS DURING THE STUDYENVIRONMENTAL CONDITIONS- Temperature (°C): 20- 24 °C- Humidity (%): 30-70%- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 ml per animal
Duration of treatment / exposure:
single application to the conjunctival sac of the right eyelid; the substance was not washed out
Observation period (in vivo):
15 d
Number of animals or in vitro replicates:
2 male, 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): noSCORING SYSTEM: Chemosis and Cornea: 0=none/normal, 1= slight, 2=well-defined, 4=severe, 5= very severeArea of cornea involved: 1 = >0; <1/4, 2= >= 1/4; < 1/2, 3= >=1/2; <3/4, 4= >=3/4Iris: 0= normal, 1= circumcorneal redness, 2= IritisConjunctivae redness: 0=none/normal, 1= slight, 2=well-defined, 4=severe
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 15 days
Remarks on result:
other: Mean 1.0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
> 0 - <= 1
Max. score:
1
Reversibility:
fully reversible within: 15d
Remarks on result:
other: Mean 0.6
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
>= 2 - <= 3
Max. score:
3
Reversibility:
fully reversible within: 15d
Remarks on result:
other: Mean 2.3
Irritation parameter:
chemosis score
Remarks:
Chemosis
Basis:
mean
Time point:
24/48/72 h
Score:
>= 0 - <= 1
Max. score:
2
Reversibility:
fully reversible within: 15d
Remarks on result:
other: Mean 0.4
Irritant / corrosive response data:
loss of corneal tissue (reversible)
Other effects:
pupil contraction, loss of hair at margins of eyelids, marginal vascularization of the cornea, small retractions in the eyelids

TABLE 1: EYE IRRITATION SCORES - INDIVIDUAL VALUES
Animal Number Sex Evaluation Interval* Corneal Opacity Area of Corneal Opacity Iris Conjunctivae Redness Chemosis Discharge
Symptoms
1 M 1 4 0 2 2 2 PC
2 M 1hour 0 0 0 2 2 3
3 F 0 0 0 2 2 3
1 M 1 4 0 2 1 1 PC
2 M 24 hours 1 2 0 2 0 1
3 F 1 2 1 3 1 1 PC
1 M 1 4 0 2 1 0 PC 
2 M 48 hours 1 4 0 2 0 0
3 F 1 3 1 3 0 1 PC/LC
1 M 1 3 1 2 1 2 PC/LC/RE
2 M 72 hours 1 3 1 2 0 0 PC/LC 
3 F 1 3 1 3 0 0 PC/LC
1 M 1 1 0 0 0 0 RE/MV/LH/LC
2 M 8 days 0 0 0 0 0 0
3 F 0 0 0 0 0 0
1 M 0 0 0 0 0 0 RE/LH
2 M 15 days 0 0 0 0 0 0
3 F 0 0 0 0 0 0
* Examinations were performed at the specified times after instillation of the test item.PC= pupils contracted, LC= loss of corneal tissue, LH= loss of hair at margins of eyelids, MV= marginal vascularization of the cornea, RE= small retractions in the eyelids
TABLE 2: EYE IRRITATION SCORES - MEAN VALUES AFTER 24, 48 AND 72 HOURS
Animal number Sex Corneal Opacity N Iris N Conjunctivae
Redness N Chemosis N
1 M 1.0 3 0.3 3 2.0 3 1.0 3
2 M 1.0 3 0.3 3 2.0 3 0.0 3
3 F 1.0 3 1.0 3 3.0 3 0.3 3
N = number of available data points.
Interpretation of results:
irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification (Commission Directive 2001/59/EC of August 06, 2001), Linalool is considered to be "not irritating" to the rabbit eye. Based upon the referred classification (Commission Regulation 1272/2008/EC of December 16, 2008), Linalool is considered to be "irritating" to the rabbit eye (Category 2).
Executive summary:

The primary eye irritation potential of Linalool was investigated based on OECD test guideline no. 405. The test item was applied by instillation of 0.1 ml into the left eye of each of three young adult Vienna White rabbits. The treated eye was not washed and the untreated eye served as control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours and 8 and 15 d after test item installation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity were 1.00 for all three animals. The individual mean scores for Iris were 0.3, 0.3, 1.0, the conjunctivae were 2.0, 2.0 and 3.0 for reddening, respectively, and 1.0, 0.0 and 0.3 for chemosis. The instillation of Linalool into the eye resulted in pupil contraction, loss of hair at margins of eyelids, marginal vascularization of the cornea, loss of corneal tissue, and small retractions in the eyelids. These effects except retractions of eyelids and loss of hair at margins of eyelids were reversible and were no longer evident 15d after treatment, the end of the observation period for all animals. Retractions of eyelids and loss of hair are, however, expected to be reversible. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye. Based upon the standard classification criteria (Commission Directive 2001/59/EC of August 06, 2001), Linalool is considered to be "not irritating" to the rabbit eye. Based upon the referred classification (Commission Regulation (EC) 1272/2008 of December 16, 2008), Linalool is considered to be "irritating" to the rabbit eye (Category 2).

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1968
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
not specified

ENVIRONMENTAL CONDITIONS
not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: undiluted test substance

Duration of treatment / exposure:
72 h
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:
Scoring of the eyes was done according to the method of Draize (Food and Drug Cosmetic Law Journal 10:722, 1955)

TOOL USED TO ASSESS SCORE:
Fluorescein was injected to check corneal damage.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The cornea opacity, iris, conjunctivae, and chemosis score was 0 in all animals after 24,48, and 72 hours.
Other effects:
- Other observations: No discharge was observed.
Interpretation of results:
other: not classified
Remarks:
based on CLP criteria
Conclusions:
Based on the results of this study, the test substance is not classified as eye irritant according to Regulation (EC) No 1272/2008 (CLP).
Executive summary:

A pre-guideline study was performed to determine the eye irritation potential of the test substance. The eye of 3 rabbits was exposed for 72 hours to the undiluted test substance. The untreated eye served as control.Cornea opacity, iris, conjunctivae, and chemosis effects were scored after 24, 48, and 72 hours according to the Draize scoring method. The cornea opacity, iris, conjunctivae, and chemosis score was 0 in all animals after 24, 48, and 72 hours. Furthermore, no discharge was observed. Under the conditions of the test, the substance is considered to be non-irritant. Based on the results of this study, the test substance is not classified as eye irritant according to Regulation (EC) No 1272/2008 (CLP).

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The current study is not performed under GLP. The study can be compared with the OECD Guideline 405, is well documented and considered scientifically acceptable.
Justification for type of information:
See attached justification
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Remarks on result:
other: 100% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.41
Max. score:
2
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: 100% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.18
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 100% concentration
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
2.29
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 100% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 30% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 30% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 30% concentration
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0.28
Max. score:
3
Remarks on result:
other: 30% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 10% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 10% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 10% concentration
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 10% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 3% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 3% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 3% concentration
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 3% concentration
Irritant / corrosive response data:
Very slight conjunctival irritation with cornea involvement, fully reversible within 7 days.
Other effects:
No data

Results relevant for evaluation of the eye irritation potential related to the EU (67/548/EEC) and CLP (1272/2008/EC) classification are given in the "overall irritation/corrosion results". This represents the mean of the animals and timepoints. Group mean animal data per timepoint are given below:

Concentration Timepoint Conjunctiva chemosis score Conjunctivae redness score Iris score Cornea opacity score
100% 24 hrs 0.33 1.67 0.67 1
  48 hrs 0 3 0.17 1
  72 hrs 0.2 2.2 0.4 1
30% 24 hrs 0 0.5 0 0
  48 hrs 0 0.17 0 0
  72 hrs 0 0.17 0 0
10% 24 hrs 0 0 0 0
  48 hrs 0 0 0 0
  72 hrs 0 0 0 0
3% 24 hrs 0 0 0 0
  48 hrs 0 0 0 0
  72 hrs 0 0 0 0

Maximum score is 110 for all concentration and timepoints.

Interpretation of results:
other: Category 2 (irritating)
Remarks:
based on CLP criteria
Conclusions:
Under the condtions of this study, it was observed that only the undiluted test material caused adverse effects on the eyes of rabbits. These effects were fully reversible within 7 days. Linalool will be classified as eye irritant according to the criteria outlined in Annex I of Regulation (EC) 1272/2008. This result is used for read-across to ethyllinalyl acetate.
Executive summary:

0.1 ml of the test substance in its natural state, or of the oil-based solution was applied in the tear duct of the left eye of each rabbit (New Zealand White) weighing between 2.2 and 3.2 kg. Six rabbits were used per concentration. Concentrations used were 100% (product in its natural state), and 30%, 10% and 3% (product in solution using groundnut oil). Observation period was 7 days.

The undiluted product was a moderate irritant to the eye. Effects were fully reversible within 7 days. As an oil-based solution the product produced no irritant effect at concentrations up to 30% in the eye. At the 100% concentration, only one conjunctivae score (at 48 hrs after exposure) was >2.5, which is the limit as set out in the EU classification directive. However, at the other timepoints the score was below 2.5 and therefore this result is neglected for EU classification. The other scores are all below the applicable limits. Based on these results, linalool will not be classified as eye irritant according to the criteria outlined in Annex VI of 67/548/EEC.

Regarding CLP classification a limit of 2.0 for the conjunctivae redness is used, which is exceeded for the 100% concentration tested (as it was shown to have a mean of 2.29 over the three timepoints). In addition, the corneal opacity score for the 100% concentration was found to be 1.0, which is as high as the limit applicable under CLP. The other scores are all below the applicable limits set out in the CLP regulation. Based on these results, linalool will have to be classified as eye irritating for the 100% concentration, but not for concentrations up to 30% according to the criteria outlined in Annex I of Regulation (EC) 1272/2008/EC. This result is used for read-across to ethyllinalyl acetate.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The current study is not performed under GLP. The study can be compared with the OECD Guideline 405, is well documented and considered scientifically acceptable.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
slightly different scoring system
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.2 to 3.2 kg

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data
Vehicle:
other: groundnut oil
Controls:
other: not relevant
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 100% (product in its natural state); 30%, 10% and 3% (product in solution using groundnut oil).

VEHICLE: groundnut oil; no further data.
Duration of treatment / exposure:
No data
Observation period (in vivo):
After 1 hour, then 1, 2, 3, 4, and 7 days after application.
Number of animals or in vitro replicates:
6 rabbits per concentration
Details on study design:
REMOVAL OF TEST SUBSTANCE: no data

SCORING SYSTEM: Numerical scoring system with degrees of severity:
1) Conjunctiva
- Lachrymal secretions (A): 0, 1, 2, 3
- Chemosis (edema) (B): 0, 1, 2, 3, 4
- Redness of the palpebral conjunctiva (C): 0, 1, 2, 3
- Coefficient of effect on conjunctiva: 2 (A+B+C)
2) Iris
- Effect on the iris (A1): 0, 1, 2
- Coefficient of the effect on the iris: 5 A1
3) Cornea
- Degree of opacity (A2): 0, 1, 2, 3, 4
- Surface of opacity (B2): 1, 2, 3, 4
- Coefficient of the effect on the cornea: 5 A2 B2

SCORING PARAMETERS USED FOR CLP CLASSIFICATION: Interpretation of the eye irritation results was performed according to the parameters used for CLP classification (1272/2008/EC), although this was not done in study report. Substance needs to be classified as eye irritant if:- Corneal opacity (degree) = 1 and/or- Iritis (lesion/effect) = 1, and/or- Conjunctival redness = 2 and/or- Conjunctival oedema (chemosis) = 2.

SCORING PARAMETERS USED FOR EU CLASSIFICATION: Interpretation of the eye irritation results was performed according to the parameters used for EU classification (67/548/EEC), although this was not done in study report. Substance needs to be classified as eye irritant if:- Cornea opacity (degree) equal to or greater than 2 but less than 3, and/or- Iris lesion (effect) equal to or greater than 1 but not greater than 1.5, and/or- Redness of the conjunctivae equal to or greater than 2.5, and/or- Edema of the conjunctivae (chemosis) equal to or greater than 2.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Remarks on result:
other: 100% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.41
Max. score:
2
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: 100% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.18
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 100% concentration
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
2.29
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 100% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 30% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 30% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 30% concentration
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0.28
Max. score:
3
Remarks on result:
other: 30% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 10% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 10% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 10% concentration
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 10% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 3% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: 3% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: 3% concentration
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: 3% concentration
Irritant / corrosive response data:
Very slight conjunctival irritation with cornea involvement, fully reversible within 7 days.
Other effects:
No data

Results relevant for evaluation of the eye irritation potential related to the EU (67/548/EEC) and CLP (1272/2008/EC) classification are given in the "overall irritation/corrosion results". This represents the mean of the animals and timepoints. Group mean animal data per timepoint are given below:

Concentration Timepoint Conjunctiva chemosis score Conjunctivae redness score Iris score Cornea opacity score
100% 24 hrs 0.33 1.67 0.67 1
  48 hrs 0 3 0.17 1
  72 hrs 0.2 2.2 0.4 1
30% 24 hrs 0 0.5 0 0
  48 hrs 0 0.17 0 0
  72 hrs 0 0.17 0 0
10% 24 hrs 0 0 0 0
  48 hrs 0 0 0 0
  72 hrs 0 0 0 0
3% 24 hrs 0 0 0 0
  48 hrs 0 0 0 0
  72 hrs 0 0 0 0

Maximum score is 110 for all concentration and timepoints.

Interpretation of results:
other: Category 2 (irritating)
Remarks:
based on CLP criteria
Conclusions:
Under the condtions of this study, it was observed that only the undiluted test material caused adverse effects on the eyes of rabbits. These effects were fully reversible within 7 days. Linalool will be classified as eye irritant according to the criteria outlined in Annex I of Regulation (EC) 1272/2008.
Executive summary:

0.1 ml of the test substance in its natural state, or of the oil-based solution was applied in the tear duct of the left eye of each rabbit (New Zealand White) weighing between 2.2 and 3.2 kg. Six rabbits were used per concentration. Concentrations used were 100% (product in its natural state), and 30%, 10% and 3% (product in solution using groundnut oil). Observation period was 7 days.

The undiluted product was a moderate irritant to the eye. Effects were fully reversible within 7 days. As an oil-based solution the product produced no irritant effect at concentrations up to 30% in the eye. At the 100% concentration, only one conjunctivae score (at 48 hrs after exposure) was >2.5, which is the limit as set out in the EU classification directive. However, at the other timepoints the score was below 2.5 and therefore this result is neglected for EU classification. The other scores are all below the applicable limits. Based on these results, linalool will not be classified as eye irritant according to the criteria outlined in Annex VI of 67/548/EEC.

Regarding CLP classification a limit of 2.0 for the conjunctivae redness is used, which is exceeded for the 100% concentration tested (as it was shown to have a mean of 2.29 over the three timepoints). In addition, the corneal opacity score for the 100% concentration was found to be 1.0, which is as high as the limit applicable under CLP. The other scores are all below the applicable limits set out in the CLP regulation. Based on these results, linalool will have to be classified as eye irritating for the 100% concentration, but not for concentrations up to 30% according to the criteria outlined in Annex I of Regulation (EC) 1272/2008/EC.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: pre-GLP study
Reason / purpose:
reference to same study
Guideline:
other: In vivo eye irritation according to Draize
Principles of method if other than guideline:
no remarks
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
not available
Vehicle:
other: unchanged or in diethylphtalate
Controls:
other: The untreated eyes served as controls.
Amount / concentration applied:
The test substance (0.1 mL) was instilled either undiluted or at a 5% concentration in diethylphthalate into the conjunctival sac of one eye of three rabbits.
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
Observations of the eyes were made immediately and 1, 2, 4, 24, 48, and 72 hours later.
Number of animals or in vitro replicates:
3
Details on study design:
Parameters evaluated were corneal opacity, pupil reaction as well as conjunctiva redness, chemosis, and discharge. Reversibility was not tested. Scoring of the eyes was done by the method of Draize: 0-normal, 1-very slight, 2-well defined, 3-moderate, 4-severe.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Reversibility:
other:
Remarks:
The effect is likely to be reversible within 21 days of observation as the effects seen were already declining at the 72 h reading.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
other:
Remarks:
The effect is likely to be reversible within 21 days of observation as the effects seen were already declining at the 72 h reading.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.67
Reversibility:
other:
Remarks:
The effect is likely to be reversible within 21 days of observation as the effects seen were already declining at the 72 h reading.
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Reversibility:
other:
Remarks:
The effect is likely to be reversible within 21 days of observation as the effects seen were already declining at the 72 h reading.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0
Reversibility:
other:
Remarks:
The effect is likely to be reversible within 21 days of observation as the effects seen were already declining at the 72 h reading.
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
For the undiluted test substance, corneal opacity grade 1 was noted in all 3 animals at the 24, 48, and 72 h readings triggering classification and labeling as an eye irritant. Pupil reaction was present at all readings. Grade 0 to grade 2 conjunctiva redness, chemosis, or discharge were noted (see Table below). The effect is likely to be reversible within 21 days of observation as the effects seen were already declining at the 72 h reading.
Other effects:
no remarks

Eye Irritation: Scores after 24, 48, and 72 h for the undiluted test item

 

 

 

Time after instillation

 

 

Animal No

1 hour

24 hours

48 hours

72 hours

Mean 24-72 (hours)

Corneal opacity

A

0

1 (4)*

1 (4)*

1 (1)*

1

 

B

0

1 (4)*

1 (4)*

1 (1)*

1

 

C

0

1 (4)*

1 (4)*

1 (2)*

1

Conjunctiva

 

 

 

 

 

 

redness

A

1

2

2

2

2

 

B

1

1

1

2

1.67

 

C

1

1

1

1

1

chemosis

A

1

1

1

0

0.67

 

B

1

0

0

0

0

 

C

1

0

0

0

0

discharge

A

3

2

2

0

1.33

 

B

2

1

1

1

1

 

C

3

1

2

0

1

*             number in brackets indicates area of cornea involved

The 5% concentration produced no signs of eye irritation at the 24, 48, and 72 h reading time points.

Interpretation of results:
other: Category 2 (irritating)
Remarks:
Based on CLP criteria
Conclusions:
Based on the criteria laid down in Regulation 1272/2008/EC, undiluted Ethyllinalool is considered an eye irritant (category 2). A 5% concentration is not irritant to eyes.
Executive summary:

Based on the criteria laid down in Regulation 1272/2008/EC, undiluted Ethyllinalool is considered an eye irritant (category 2). A 5% concentration is not irritant to eyes.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
See attached justification
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, and #3
Time point:
24/48/72 h
Score:
1
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.67
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
For the undiluted test substance, corneal opacity grade 1 was noted in all 3 animals at the 24, 48, and 72 h readings triggering classification and labeling as an eye irritant. Pupil reaction was present at all readings. Grade 0 to grade 2 conjunctiva redness, chemosis, or discharge were noted (see Table below). The effect is likely to be reversible within 21 days of observation as the effects seen were already declining at the 72 h reading.
Other effects:
no remarks

Eye Irritation: Scores after 24, 48, and 72 h for the undiluted test item

 

 

 

Time after instillation

 

 

Animal No

1 hour

24 hours

48 hours

72 hours

Mean 24-72 (hours)

Corneal opacity

A

0

1 (4)*

1 (4)*

1 (1)*

1

 

B

0

1 (4)*

1 (4)*

1 (1)*

1

 

C

0

1 (4)*

1 (4)*

1 (2)*

1

Conjunctiva

 

 

 

 

 

 

redness

A

1

2

2

2

2

 

B

1

1

1

2

1.67

 

C

1

1

1

1

1

chemosis

A

1

1

1

0

0.67

 

B

1

0

0

0

0

 

C

1

0

0

0

0

discharge

A

3

2

2

0

1.33

 

B

2

1

1

1

1

 

C

3

1

2

0

1

*             number in brackets indicates area of cornea involved

The 5% concentration produced no signs of eye irritation at the 24, 48, and 72 h reading time points.

Interpretation of results:
other: Category 2 (irritating)
Remarks:
based on CLP criteria
Conclusions:
Based on the criteria laid down in Regulation 1272/2008/EC, undiluted Ethyllinalool is considered an eye irritant (category 2). A 5% concentration is not irritant to eyes.
Executive summary:

Based on the criteria laid down in Regulation 1272/2008/EC, undiluted Ethyllinalool is considered an eye irritant (category 2). A 5% concentration is not irritant to eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Four studies are available for this endpoint, of which the key study was performed with ethyllinalyl acetate. Ethyllinalyl acetate was tested according to OECD 439 with the in vitro reconstructed human epidermis model. 16µL test substance was applied and the tissues were exposed for 42 minutes at room temperature, in triplicate. After exposure the tissues were rinsed with PBS. After 42 hours post-incubation a MTT assay was performed to determine the cell viability. Negative and positive controls were run in parallel and acceptance criteria were met. The mean cell viability was determined to be 9.1%. Based on the results of this study, the substance is considered to be at least a skin irritant.

The first supporting study is an in vivo skin irritation test performed according to OECD 404 and in compliance with GLP. Single 4-hour-exposure of Linalool (100% concentration) under semi-occlusive conditions in three independent experiments caused slight irritation on rabbit skin. A mean erythema score (24-72h) of at least 2 for at least 24 hours was observed in rabbits one of the three tests. Mean erythema values (24-72h) for each of the animals showed a maximum of 2 in all three tests. Erythema was still visible after 7 days. In addition desquamation was noted. Mean oedema scores were (24-72h) <1.4. Mean oedema values (24 -72h) for each of the animals showed a maximum of 1.7 in all three tests. Marked and slight desquamation from skin surface appeared at day 1, 2, 3 and 7 days. The skin responses (erythema and/or oedema) did not disappear in all animals after 7 days. Based on this, linalool is considered to be irritating to the rabbit skin. This result is read-across to ethyllinalyl acetate.

 

The second supporting study was pre-guideline study performed to determine the skin irritating potential of the test substance. The intact skin of 3 rabbits was exposed for 72 hours to the undiluted test substance. The untreated skin served as control. Erythema and edema was scored after 24 and 72 hours according to the Draize scoring method. In two animals well-defined erythema was observed after 24 hours and very slight erythema was observed after 72 hours. Very slight erythema after 24 and 72 hours was observed in the third animal. No edema was observed after 24 and 72 hours. This in vivo result supports the conclusion to consider ethyllinalyl acetate an irritant to skin.

 

A third supporting study was performed with read across-substance ethyllinalool. A pre-guideline study was performed to determine the skin irritation potential of the test substance. The intact skin of 3 rabbits was exposed for 72 hours to the undiluted test substance. The untreated skin served as control. Erythema and edema was scored after 24 and 72 hours according to the Draize scoring method. Results for abraded and non-abraded skin were comparable. No edema were seen after application of the undiluted test item. Grade 1 to 2 erythema were seen after 24 hours. Grade 1 erythema was seen after 72 hours. The results strongly suggest that Ethyllinalool should be considered a skin irritant.

 

Eye irritation

Four studies are available for this endpoint, of which one was performed with ethyllinalyl acetate, two were performed for the read-across substance linalool and another was performed for the read-across substance ethyllinalool. These studies are used in a weight of evidence approach. The first available study (Colaianni, 1968) is a pre-guideline study performed to determine the eye irritation potential of ethyllinalyl acetate. The eye of 3 rabbits was exposed for 72 hours to the undiluted test substance. The untreated eye served as control. Cornea opacity, iris, conjunctivae, and chemosis effects were scored after 24, 48, and 72 hours according to the Draize scoring method. The cornea opacity, iris, conjunctivae, and chemosis score was 0 in all animals after 24, 48, and 72 hours. Furthermore, no discharge was observed. Under the conditions of the test, the substance is considered to be non-irritant.

 

In the second study (Julou, 1974), eye irritation was study according to a method similar to OECD405. 0.1 ml of linalool was applied in the tear duct of the left eye of each rabbit (New Zealand White). Six rabbits were used per concentration. Concentrations used were 100% (product in its natural state), 30%, 10% and 3% (product in solution using groundnut oil). Observation period was 7 days. The undiluted product was found to be a moderate irritant to the eye. Effects were fully reversible within 7 days. As an oil-based solution the product produced no irritant effect at concentrations up to 30% in the eye. At the 100% concentration, only one conjunctivae score (at 48 hrs after exposure) was >2.5. This effect was fully reversible within 7 days. Regarding CLP classification a limit of 2.0 for the conjunctivae redness is used, which is exceeded for the 100% concentration tested (as it was shown to have a mean of 2.29 over the three timepoints). In addition, the corneal opacity score for the 100% concentration was found to be 1.0, which is as high as the limit applicable under CLP. The other scores are all below the applicable limits set out in the CLP regulation. Based on these results, 100% linalool should be considered an eye irritant.

 

In the third available study (BASF, 1988), the primary eye irritation potential of Linalool was investigated based on OECD test guideline no. 405. The test item was applied by instillation of 0.1 ml into the left eye of each of three young adult Vienna White rabbits. The treated eye was not washed and the untreated eye served as control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours and 8 and 15 d after test item installation. The individual mean scores for corneal opacity were 1.00 for all three animals. The individual mean scores for the iris were 0.3, 0.3, 1.0, the conjunctivae were 2.0, 2.0 and 3.0 for reddening, respectively, and 1.0, 0.0 and 0.3 for chemosis. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed. The test item is therefore considered not to induce significant or irreversible damage to the rabbit eye. Nevertheless, based on the eye scores and the applicable CLP criteria, Linalool is considered to be irritating to the rabbit eye.

 

In the fourth study (Colaianni, 1968) is a pre-guideline study performed to determine the eye irritation potential of ethyllinalool. The eye of 3 rabbits was exposed for 72 hours to 5% or the undiluted test substance. The untreated eye served as control. Cornea opacity, conjunctivae redness, and chemosis effects were scored after 24, 48, and 72 hours according to the Draize scoring method. No effects were observed after exposure to 5% test substance. In the study performed with the undiluted substance effects on the eyes were observed. The cornea opacity score was 1 for all animals after 24, 48, and 72 hours. Conjunctivae redness was observed in all animals with an averagescore over 24-72h of 2, 1.67, and 1. Chemosis was observed in 1 animal with an average score over 24-72h of 0.67 and the effects were fully reversible within 72h. Under the conditions of the test, the substance is considered to be an eye irritant.

 

The results for the two linalool studies and the ethyllinalool study were read-across to ethyllinalyl acetate. Taking the four test results together it is concluded that ethyllinalyl acetate should be regarded as an eye irritant, despite of the negative result found in the study with ethyllinalyl acetate itself.

Justification for classification or non-classification

Based on the available data, ethyllinalyl acetate is considered to be a skin irritant (Category 2 / H315) and eye irritant (Category 2 / H319) in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).