Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From May 10 to 24, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD guideline 405 without any deviation.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): BETA-PINENE
NOTE: Due to an industry habit inherited from the past, the test material was referenced as beta pinene whereas it was actually (-)-beta pinene.
Physical state: Colorless-slightly amber liquid
Analytical purity: 98.8%
Lot/batch No.: EG12R
Production date: 21 April 2010
Date received: May 07, 2010
Expiration date of the lot/batch: April 21, 2011
Storage condition of test material: 6 ± 3 °C, protected from light; kept under nitrogen

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: 2.08-3.07 kg
- Housing: Each animal housed in individual box
- Diet: Foodstuff (SDS - C15); ad libitum
- Water: 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: 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):
Eight 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:
other: 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 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:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 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:
other: 24, 48 and 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:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 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:
other: 24, 48 and 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 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:
other: 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
- Moderate redness of the conjunctivae associated with moderate to severe chemosis was noted in all treated animals after 1 hour of instillation; irritation completely resolved within 8 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

2

0

0

24 hours

1

1

0

0

48 hours

1

1

0

0

72 hours

2

1

0

0

Day 4

2

1

0

0

Day 7

1

1

0

0

Day 8

0

0

0

0

Mean (24, 48 and 72 hours)

1.3

1

0

0

2

1 hour

3

2

0

0

24 hours

2

1

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

0

0

3

1 hour

3

2

0

0

24 hours

2

2

0

0

48 hours

1

2

0

0

72 hours

0

2

0

0

Day 4

0

1

0

0

Day 7

0

0

0

0

Mean (24, 48 and 72 hours)

1

2

0

0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, (-)-BETA-PINENE is not classified as irritating to eyes 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 (-)-beta-pinene 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, 7 and 8 days after dosing.

 

Instillation of (-)-BETA-PINENE resulted in moderate redness of the conjunctivae associated with moderate to severe chemosis in all treated animals after 1 hour of instillation. The irritation completely resolved within 8 days. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 1, 1, 2 for conjunctivae score and 1.3, 1, 1 for chemosis score.

 

Under the test conditions, (-)-beta-pinene is not classified as irritating to eyes according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.