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Diss Factsheets

Administrative data

Description of key information

Skin irritation: Irritating (OECD 404)
Eye irritation: Irritating (OECD 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981, 1992
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: albino
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: 100 %
Duration of treatment / exposure:
4 hours
Observation period:
1 hour, 1, 2, 3, and 7 days
Number of animals:
Test 1: 3
Test 2 and 3: 4
Details on study design:
TEST SITE
- Area of exposure: Flank
- % coverage: No data
- Type of wrap: Semi-occlusive patches (multi-patch)

SCORING SYSTEM: Draize scale, following OECD Test Guideline 404 (Erythema and Eschar formation / Oedema formation). Maximum possible score: 4
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Test 3
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 3
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 3
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
Test 3
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 3
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 3
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 3
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 3
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 2
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 2
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 2
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 2
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 2
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 2
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 2
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 2
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 1
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 1
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 1
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 1
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Remarks:
Test 1
Irritant / corrosive response data:
Marked and slight desquamation from skin surface appeared as follows:
Test 1: at day 2, 3 and 7 (1 animal marked)
Test 2: at day 1, 2, 3,and 7 (2 animals marked, 1 animal slight)
Test 3: at day 3 and 7 (1 animal marked, 3 animals slight)
Other effects:
No data

Mean values (24 -72h) per animal per endpoint per test (used for CLP classification):





























































































































































































Irritation parameterBasisTime pointScoreReversibilityRemarks
Erythema scoreAnimal #124-72 hrs2Not fully reversible within: 7 daysTest 1
Oedema scoreAnimal #124-72 hrs2Not fully reversible within: 7 daysTest 1
Erythema scoreAnimal #224-72 hrs2Not fully reversible within: 7 daysTest 1
Oedema scoreAnimal #224-72 hrs1.3Not fully reversible within: 7 daysTest 1
Erythema scoreAnimal #324-72 hrs1.7Fully revesible within: 7 daysTest 1
Oedema scoreAnimal #324-72 hrs1Not fully reversible within: 7 daysTest 1
Erythema scoreAnimal #124-72 hrs2Not fully reversible within: 7 daysTest 2
Oedema scoreAnimal #124-72 hrs1.7Not fully reversible within: 7 daysTest 2
Erythema scoreAnimal #224-72 hrs2Not fully reversible within: 7 daysTest 2
Oedema scoreAnimal #224-72 hrs1.7Fully revesible within: 7 daysTest 2
Erythema scoreAnimal #324-72 hrs2Not fully reversible within: 7 daysTest 2
Oedema scoreAnimal #324-72 hrs1Not fully reversible within: 7 daysTest 2
Erythema scoreAnimal #424-72 hrs2Not fully reversible within: 7 daysTest 2
Oedema scoreAnimal #424-72 hrs1Not fully reversible within: 7 daysTest 2
Erythema scoreAnimal #124-72 hrs1Fully revesible within: 7 daysTest 3
Oedema scoreAnimal #124-72 hrs0-Test 3
Erythema scoreAnimal #224-72 hrs2Not fully reversible within: 7 daysTest 3
Oedema scoreAnimal #224-72 hrs1Fully revesible within: 7 daysTest 3
Erythema scoreAnimal #324-72 hrs2Fully revesible within: 7 daysTest 3
Oedema scoreAnimal #324-72 hrs0.7Fully revesible within: 7 daysTest 3
Erythema scoreAnimal #424-72 hrs1.7Fully revesible within: 7 daysTest 3
Oedema scoreAnimal #424-72 hrs0-Test 3
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
This interpreation was based on a mean erythema score (24-72h) of at least 2 for at least 24 hours was observed in rabbits in 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 these data it can be assumed that linalool is irritating to the rabbit skin. The substance needs to be classified as skin irritant according to the criteria outlined in Annex I of Regulation (EC) 1272/2008.
Executive summary:

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 these data it can be assumed that linalool is irritating to the rabbit skin. The substance needs to be classified as skin irritant according to the criteria outlined in Annex I of Regulation (EC)1272/2008.

 

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:
experimental study
Adequacy of study:
weight of evidence
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
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.
Qualifier:
equivalent or similar to guideline
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 applied: 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 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.

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.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.18
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 100% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 30% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 10% concentration
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 3% concentration
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
2.29
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:
0.28
Remarks on result:
other: 30% concentration
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 10% concentration
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 3% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.41
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: 100% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 30% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 10% concentration
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 3% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Remarks on result:
other: 100% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 30% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: 10% concentration
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
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:
Category 2 (irritating to eyes) based on GHS 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:
08.08.1988-26.09.1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Study based on OECD guideline 405 (1981)
Qualifier:
equivalent or similar to guideline
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 in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20-24 °C and 30-70% relative humidity.
- Diet: 130 g per animal per day, Kliba 341, 4mm
- Water: 250 mL per animal per day
- Acclimation period: At least 8 days before the beginning of the study: Same housing conditions as during the study.

ENVIRONMENTAL 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 applied: 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): no

SCORING SYSTEM: Chemosis and Cornea: 0=none/normal, 1= slight, 2=well-defined, 4=severe, 5= very severe
Area of cornea involved: 1 = >0; <1/4, 2= >= 1/4; < 1/2, 3= >=1/2; <3/4, 4= >=3/4
Iris: 0= normal, 1= circumcorneal redness, 2= Iritis
Conjunctivae redness: 0=none/normal, 1= slight, 2=well-defined, 4=severe

Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
positive indication of irritation
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 NumberSexEvaluation Interval*Corneal OpacityArea of Corneal OpacityIrisConjunctivae RednessChemosisDischarge 
Symptoms
1M 140222PC
2M1hour000223 
3F 000223 
          
1M 140211PC
2M24 hours120201 
3F 121311PC
          
1M 140210PC 
2M48 hours140200 
3F 131301PC/LC
          
1M 131212PC/LC/RE
2M72 hours131200PC/LC 
3F 131300PC/LC
          
1M 110000RE/MV/LH/LC
2M8 days000000 
3F 000000 
          
1M 000000RE/LH
2M15 days000000 
3F 000000 
  
 
* 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 numberSexCorneal OpacityNIrisNConjunctivae
RednessNChemosisN
          
1M1.030.332.031.03
2M1.030.332.030.03
3F1.031.033.030.33
N = number of available data points.     
       
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
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 conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

For the endpoint of skin irritation/corrosion a test conducted in rabbits according to OECD Guideline 404, 1981, 1992 and under GLP Standards was selected as key study. Single 4-hour-exposure of Linalool (100% concentration) under semi-occlusive conditions in three independent experiments caused slight irritation on rabbit skin. Group mean erythema scores (24 -72h) were 1.9, 2, and 1.7, respectively. Group mean oedema scores (24 - 72h) were 1.4, 1.4, and 0.4, respectively. Maximum scores were 2 for erythema and oedema. 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 after 7 days. Based on these data it is concluded that linalool is irritant to rabbit skin. Linalool has to be classified as a skin irritant according to Regulation (EC) No. 1272/2008.


The primary eye irritation potential of Linalool was studied in albino rabbits. 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 irritant to the eye. Group mean scores for conjunctiva phemosis were 0.18, 0, 0, and 0 for the undiluted product, 30%, 10%, and 3% concentration, respectively. Group mean scores (24 -72h) for conjunctiva redness were 2.29, 0.28, 0, and 0, respectively. Iris scores were 0.41, 0, 0, and 0, respectively. Corneal opacity was 1.1, 0, 0, and 0, respectively. Effects were fully reversible within 7 days. As an oil-based solution the product produced no effect requiring classification as eye irritant at a concentration of 30% or lower in the eye.


Linalool has to be classified as an eye irritant according to Regulation (EC) 1272/2008.


In a 2nd supporting study, 3 rabbits were treated with pure linalool. Effects seen require classification as eye irritant according to 1272/2008/EC.


The respiratory irritation was not studied for Linalool.



Effects on skin irritation/corrosion: irritating

Effects on eye irritation:
irritating


 

Justification for classification or non-classification

The irritation/corrosion tests indicate that Linalool is irritating to the rabbit skin and eye. Therefore, it can be concluded that the substance is irritating to the skin and irritating to the eye and therefore does need to be classified as such according to the criteria under Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/1182.