(1R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

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. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(-)-pin-2(10)-ene

EC Number:

242-060-2

EC Name:

(-)-pin-2(10)-ene

Cas Number:

18172-67-3

IUPAC Name:

6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane

Constituent 2

Reference substance name:

(1S,5S)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane

IUPAC Name:

(1S,5S)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane

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: April 21, 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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

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 the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° 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 the test item 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 the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° 1272 /2008.