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EC number: 227-813-5 | CAS number: 5989-27-5
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From May 10 to 21, 2010
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- GLP study conducted in compliance with OECD guideline 405 with minor deviation: no data on tool used to asses score
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- no data on tool used to asses score
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- no data on tool used to asses score
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- (R)-p-mentha-1,8-diene
- EC Number:
- 227-813-5
- EC Name:
- (R)-p-mentha-1,8-diene
- Cas Number:
- 5989-27-5
- Molecular formula:
- C10H16
- IUPAC Name:
- 4-isopropenyl-1-methylcyclohexene
- Reference substance name:
- 7-methyl-3-methyleneocta-1,6-diene
- EC Number:
- 204-622-5
- EC Name:
- 7-methyl-3-methyleneocta-1,6-diene
- Cas Number:
- 123-35-3
- Molecular formula:
- C10H16
- IUPAC Name:
- 7-methyl-3-methyleneocta-1,6-diene
- Reference substance name:
- (S)-3,7-dimethyl-1,6-octadien-3-ol
- EC Number:
- 204-810-7
- EC Name:
- (S)-3,7-dimethyl-1,6-octadien-3-ol
- Cas Number:
- 126-90-9
- Molecular formula:
- C10H18O
- IUPAC Name:
- 3,7-dimethylocta-1,6-dien-3-ol
- Reference substance name:
- (R)-3,7-dimethyl-1,6-octadien-3-ol
- EC Number:
- 204-811-2
- EC Name:
- (R)-3,7-dimethyl-1,6-octadien-3-ol
- Cas Number:
- 126-91-0
- Molecular formula:
- C10H18O
- IUPAC Name:
- 3,7-dimethylocta-1,6-dien-3-ol
- Reference substance name:
- (-)-pin-2(3)-ene
- EC Number:
- 232-077-3
- EC Name:
- (-)-pin-2(3)-ene
- Cas Number:
- 7785-26-4
- Molecular formula:
- C10H16
- IUPAC Name:
- (1S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
- Reference substance name:
- (+)-pin-2(3)-ene
- EC Number:
- 232-087-8
- EC Name:
- (+)-pin-2(3)-ene
- Cas Number:
- 7785-70-8
- Molecular formula:
- C10H16
- IUPAC Name:
- (1R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
- Reference substance name:
- p-mentha-1,4-diene
- EC Number:
- 202-794-6
- EC Name:
- p-mentha-1,4-diene
- Cas Number:
- 99-85-4
- Molecular formula:
- C10H16
- IUPAC Name:
- 1-isopropyl-4-methylcyclohexa-1,4-diene
- Reference substance name:
- 3-isopropyl-(6S)-methylenecyclohexene
- Cas Number:
- 6153-16-8
- Molecular formula:
- C10H16
- IUPAC Name:
- 3-isopropyl-(6S)-methylenecyclohexene
- Reference substance name:
- 3-isopropyl-(6R)-methylenecyclohexene
- Cas Number:
- 6153-17-9
- Molecular formula:
- C10H16
- IUPAC Name:
- 3-isopropyl-(6R)-methylenecyclohexene
- Reference substance name:
- (1S)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene
- EC Number:
- 207-856-6
- EC Name:
- (1S)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene
- Cas Number:
- 498-15-7
- Molecular formula:
- C10H16
- IUPAC Name:
- (1S,6R)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene
- Reference substance name:
- (1R,6S)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene
- Cas Number:
- 20296-50-8
- Molecular formula:
- C10H16
- IUPAC Name:
- (1R,6S)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene
- Reference substance name:
- (-)-pin-2(10)-ene
- EC Number:
- 242-060-2
- EC Name:
- (-)-pin-2(10)-ene
- Cas Number:
- 18172-67-3
- Molecular formula:
- C10H16
- IUPAC Name:
- (1S,5S)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane
- Reference substance name:
- p-cymene
- EC Number:
- 202-796-7
- EC Name:
- p-cymene
- Cas Number:
- 99-87-6
- Molecular formula:
- C10H14
- IUPAC Name:
- 1-isopropyl-4-methylbenzene
- Reference substance name:
- p-mentha-1,4(8)-diene
- EC Number:
- 209-578-0
- EC Name:
- p-mentha-1,4(8)-diene
- Cas Number:
- 586-62-9
- Molecular formula:
- C10H16
- IUPAC Name:
- 4-isopropylidene-1-methylcyclohexene
- Reference substance name:
- (1R,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane
- Cas Number:
- 19902-08-0
- Molecular formula:
- C10H16
- IUPAC Name:
- (1R,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane
- Test material form:
- liquid
- Details on test material:
- Batch No.: EX6R
Purity: 95.2 %
Name of test material (as cited in study report): D-LIMONENE
Physical state: colourless to slightly yellow liquid
Storage conditions: 2°C to 8 °C, protected from light and under nitrogen
Constituent 1
impurity 1
impurity 2
impurity 3
impurity 4
impurity 5
impurity 6
impurity 7
impurity 8
impurity 9
impurity 10
impurity 11
impurity 12
impurity 13
impurity 14
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Elevage de Gerome, Quartier Labaste, France
- Age at study initiation: 11 or 13 weeks
- Weight at study initiation: 2.04-3.05 kg
- Housing: Each animal housed in individual box
- Diet (e.g. ad libitum): Foodstuff (SDS - C15); ad libitum
- Water (e.g. ad libitum): Tap water (public distribution system); ad libitum
- Acclimation period: Five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hour):15/hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume with unit): 0.1 mL - Duration of treatment / exposure:
- No washing was done
- Observation period (in vivo):
- Seven days
- Number of animals or in vitro replicates:
- Three males
- Details on study design:
- SCORING SYSTEM:
Chemosis
No swelling …0
Slight swelling, including the nictitating membrane…1
Swelling with eversion of the eyelid...2
Swelling with eyelid half-closed…3
Swelling with eyelid more than half-closed…4
Discharge
No discharge…0
Slight discharge (normal slight secretion in the inner corner not to be taken into account)…1
Discharge with moistening of the eyelid and neighboring hairs…2
Discharge with moistening of the eyelids and large areas around the eye…3
Redness
Blood vessel normal…0
Vessels significantly more prominent than normal…1
Vessels individually distinguishably with difficulty
Generally red coloration….2
Generally deep red coloration….3
Iris
Normal…0
Iris significantly more wrinkled than normal, congestion, swelling of the iris which continues to react to light, even slowly…1
No reaction to light, haemorrhage, significant damage (any or all of these characteristics)…2
Cornea: degree of opacity
No modification visible either directly or after instillation of fluorescein (no loss of glint or polish)…0
Translucent areas (diffuse or disseminated), iris details clearly visible…1
Early identifiable translucent area, iris details slightly obscured…2
Opalescent area, no iris details visible, pupil outline scarcely distinguishable…3
Total corneal opacity, completely obscuring the iris and pupil…4
Cornea: extent of opacity
Opaque area present but covering one quarter or less…1
Between one quarter and half…2
Between half and three quarters…3
Between three quarters and the entire surface…4
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 2 days
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: not applicable
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 2 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 4 days
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: not applicable
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 3 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 4 days
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: not applicable
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: not applicable
- Irritant / corrosive response data:
- - Slight to moderate redness of conjunctivae associated with moderate chemosis was noted within 1 hour of instillation; irritation completely resolved within 7 days.
- See table 1 for more details - Other effects:
- No data
Any other information on results incl. tables
Table 1: Individual and mean scores of conjunctivae, iris and cornea
Animal |
Time after treatment |
Conjunctivae |
Iris |
Cornea |
|
Chemosis |
Redness |
Lesion |
Opacity |
||
1 |
1 hour |
2 |
1 |
0 |
0 |
24 hours |
1 |
1 |
0 |
0 |
|
48 hours |
1 |
0 |
0 |
0 |
|
72 hours |
1 |
0 |
0 |
0 |
|
Day 4 |
1 |
0 |
0 |
0 |
|
Day 7 |
0 |
0 |
0 |
0 |
|
Mean (24, 48 and 72 hours) |
1 |
0.3 |
0 |
0 |
|
2 |
1 hour |
2 |
2 |
0 |
0 |
24 hours |
1 |
1 |
0 |
0 |
|
48 hours |
0 |
1 |
0 |
0 |
|
72 hours |
0 |
1 |
0 |
0 |
|
Day 4 |
0 |
0 |
0 |
0 |
|
Mean (24, 48 and 72 hours) |
0.3 |
1 |
0 |
0 |
|
3 |
1 hour |
2 |
2 |
0 |
0 |
24 hours |
2 |
2 |
0 |
0 |
|
48 hours |
1 |
1 |
0 |
0 |
|
72 hours |
0 |
1 |
0 |
0 |
|
Day 4 |
0 |
0 |
0 |
0 |
|
Mean (24, 48 and 72 hours) |
1 |
1.3 |
0 |
0 |
|
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- d-Limonene is not classified as irritating to the eye according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.
- Executive summary:
In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, three male rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted d-limonene in one of the eyes while the other eye corresponded to the control. The eyes were examined for irritation scores at 1 hour and 1, 2, 3, 4 and 7 days after dosing.
Instillation of d-limonene resulted in slight to moderate redness of conjunctivae associated with moderate chemosis in all treated animals after 1 hour of instillation. The irritation completely resolved within 7 days. Mean individual scores at 24, 48 and 72 hours after exposure for the 3 animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.3, 1, 1.3 for conjunctivae score and 1, 0.3, 1 for chemosis score.
Therefore, d-limonene is not classified as irritating to the eyes according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.
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