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EC number: 201-134-4 | CAS number: 78-70-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
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- Boiling point
- Density
- Particle size distribution (Granulometry)
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- Endpoint summary
- Stability
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- 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
Skin irritation: Irritating (OECD 404)
Eye irritation: Irritating (OECD 405)
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- 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
- 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.
Reference
Mean values (24 -72h) per animal per endpoint per test (used for CLP classification):
Irritation parameter | Basis | Time point | Score | Reversibility | Remarks |
Erythema score | Animal #1 | 24-72 hrs | 2 | Not fully reversible within: 7 days | Test 1 |
Oedema score | Animal #1 | 24-72 hrs | 2 | Not fully reversible within: 7 days | Test 1 |
Erythema score | Animal #2 | 24-72 hrs | 2 | Not fully reversible within: 7 days | Test 1 |
Oedema score | Animal #2 | 24-72 hrs | 1.3 | Not fully reversible within: 7 days | Test 1 |
Erythema score | Animal #3 | 24-72 hrs | 1.7 | Fully revesible within: 7 days | Test 1 |
Oedema score | Animal #3 | 24-72 hrs | 1 | Not fully reversible within: 7 days | Test 1 |
Erythema score | Animal #1 | 24-72 hrs | 2 | Not fully reversible within: 7 days | Test 2 |
Oedema score | Animal #1 | 24-72 hrs | 1.7 | Not fully reversible within: 7 days | Test 2 |
Erythema score | Animal #2 | 24-72 hrs | 2 | Not fully reversible within: 7 days | Test 2 |
Oedema score | Animal #2 | 24-72 hrs | 1.7 | Fully revesible within: 7 days | Test 2 |
Erythema score | Animal #3 | 24-72 hrs | 2 | Not fully reversible within: 7 days | Test 2 |
Oedema score | Animal #3 | 24-72 hrs | 1 | Not fully reversible within: 7 days | Test 2 |
Erythema score | Animal #4 | 24-72 hrs | 2 | Not fully reversible within: 7 days | Test 2 |
Oedema score | Animal #4 | 24-72 hrs | 1 | Not fully reversible within: 7 days | Test 2 |
Erythema score | Animal #1 | 24-72 hrs | 1 | Fully revesible within: 7 days | Test 3 |
Oedema score | Animal #1 | 24-72 hrs | 0 | - | Test 3 |
Erythema score | Animal #2 | 24-72 hrs | 2 | Not fully reversible within: 7 days | Test 3 |
Oedema score | Animal #2 | 24-72 hrs | 1 | Fully revesible within: 7 days | Test 3 |
Erythema score | Animal #3 | 24-72 hrs | 2 | Fully revesible within: 7 days | Test 3 |
Oedema score | Animal #3 | 24-72 hrs | 0.7 | Fully revesible within: 7 days | Test 3 |
Erythema score | Animal #4 | 24-72 hrs | 1.7 | Fully revesible within: 7 days | Test 3 |
Oedema score | Animal #4 | 24-72 hrs | 0 | - | Test 3 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- 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
- 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
- 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).
Referenceopen allclose all
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.
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. | |||||||||
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.
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