3,7-dimethyloctan-3-yl acetate

Endpoint summary

Description of key information

Skin irritation (OECD TG 404): not irritating

Eye irritation (similar to OECD TG 405): irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

November 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield Farms (UK) Limited, Froxfield, Hampshire
- Weight at study initiation: 2.7, 3.2, and 3.4 kg
- Housing: individually in grid bottomed metal cages
- Diet: An antibiotic free rabbit diet (SQC Standard rabbit pellets produced by Special Diets Services, Witham, Essex), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 24
- Humidity (%): 51 - 74
- Air changes: room was airconditioned
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: undiluted

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm square patch of surgical lint located on the dorsal surfaces of the trunk.
- % coverage: not specified
- Type of wrap if used: The patch was held in position by encircling the trunk of the animal with a length of ’Elastoplast’ elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The treated site was gently cleansed with water.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Examinations were made 1, 24, 48 and 72 hours after exposure and additional observations were made 7 and 14 days after exposure.

SCORING SYSTEM:
- Method of calculation: Draize’s scale was used to score the Erythema, eschar and Oedema formation. The Primary Irritation Index was calculated by totalling the erythema and oedema scores recorded at the 24 and 72 hour examinations for all 3 animals (12 scores in total) and dividing this value by 6.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritant / corrosive response data:

Within one hour of patch removal, well defined erythema and slight or moderate oedema were apparent at the treated site on all 3 rabbits. Slight or well defined erythema and slight oedema persisted in all animals 24 and 48 hours after patch removal and there was no decrease in the intensity of irritation at the 72 hour examination. Seven days after dosing, erythema was well defined to moderate and oedema was slight to moderate. Slight eschar formation was noted on the borders of the treated site on one animal (no. 3) at this time. At the final examination, 14 days after dosing, very slight erythema persisted at the treated site on one rabbit (no. 1) and no fur growth had occurred at the treated site. Very slight erythema and oedema were still apparent on a second animal (no. 3). There was no sign of irritation at the treated site on the third rabbit (no.2) but fur growth over the site was reduced. The Primary Irritation Index was calculated to be 3.8.

Interpretation of results:

other: not classified

Remarks:

based on CLP criteria

Conclusions:

Under the conditions of the test, the substance was found to cause slight to moderate irritation in the animals tested, but the mean erythema and edema scores do not exceed the limits as specified in CLP. Based on these results, the test substance does not need to be classified as skin irritant in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Executive summary:

A skin irritation study was performed according to OECD TG 404 and in compliance with GLP. Three New Zealand white rabbits were exposed 0.5 mL undiluted test substance for 4 hours under semi-oclussive conditions. After 4 hours the test substance was removed with water. Erythema and oedema were scored 1, 24, 48, and 72 hours and 7 and 14 days after exposure. Within one hour of patch removal, well defined erythema and slight or moderate oedema were apparent at the treated site on all 3 rabbits. Slight or well defined erythema and slight oedema persisted in all animals 24 and 48 hours after patch removal and there was no decrease in the intensity of irritation at the 72 hour examination. Seven days after dosing, erythema was well defined to moderate and oedema was slight to moderate. Slight eschar formation was noted on the borders of the treated site on one animal (no. 3) at this time. At the final examination, 14 days after dosing, very slight erythema persisted at the treated site on one rabbit (no. 1) and no fur growth had occurred at the treated site. Very slight erythema and oedema were still apparent on a second animal (no. 3). There was no sign of irritation at the treated site on the third rabbit (no.2) but fur growth over the site was reduced. These effects are not considered to be part of a persisting inflammatory response. Under the conditions of the test, the substance was found to cause slight to moderate irritation in the animals tested, but the mean erythema and edema scores do not exceed the limit as specified in CLP. Based on these results, the test substance does not need to be classified as skin irritant in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

See attached justification

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 1

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 3

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.4

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Test 3

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 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

Interpretation of results:

other: not classified

Remarks:

based on CLP criteria

Conclusions:

Under the conditions of this study, mean erythema and edema scores in the animals in each test were not above 2.3 for the timepoints concerned for classification. However, some effects did not disappear within the 7 days observation period. Therefore the substance is considered to be irritating to skin and should be classified as such based on the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC). This result was used for read-across to tetrahydrolinalyl acetate.

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 linalool is considered to be 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. This result was used for read-across to tetrahydrolinalyl acetate.

Reference 3

Endpoint:

skin 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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981, 1992

Deviations:

yes

Remarks:

Observation period 7 days instead of 14 days

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(s) applied (volume): 0.5 ml
- Concentration (if solution): 100 %

Duration of treatment / exposure:

4 hours

Observation period:

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 if used: semi-occlusive patches (multi-patch)

OBSERVATION TIME POINTS
1 hour and 1, 2, 3 and 7 days

SCORING SYSTEM: Draize scale, following OECD Test Guideline 404 (Erythema and Eschar formation / Oedema formation). Maximum possible score: 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.9

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 1

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 1

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:

other: Test 2

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.4

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 2

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Test 3

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.4

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Test 3

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 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

Interpretation of results:

other: not classified

Remarks:

based on CLP criteria

Conclusions:

Under the conditions of this study, mean erythema and edema scores in the animals in each test were not above 2.3 for the timepoints concerned for classification. However, some effects did not disappear within the 7 days observation period. Therefore the substance is considered to be irritating to skin and should be classified as such based on the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

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 linalool is considered to be 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:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study based on OECD guideline 405 (1981)

Reason / purpose for cross-reference:

reference to same study

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 I N FULLY AIR-CONDITIONED ROOMS. CENTRAL AIR-CONDITIONING GUARANTEED ARANGE OF 2 0 - 2 4 DEGREES CELSIUS FOR TEMPERATURE AND OF 3 0 - 70% FOR RELATIVE HUMIDITY.- Diet (e.g. ad libitum): 130 g per animal per day, Kliba 341, 4mm- Water (e.g. ad libitum): 250 ml per animal per day- Acclimation period: AT LEAST 8 DAYS BEFORE THE BEGINNING OF THE STUDV: SAME HOUSING CONDITIONS AS DURING THE STUDYENVIRONMENTAL 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(s) applied (volume or weight with unit): 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): noSCORING SYSTEM: Chemosis and Cornea: 0=none/normal, 1= slight, 2=well-defined, 4=severe, 5= very severeArea of cornea involved: 1 = >0; <1/4, 2= >= 1/4; < 1/2, 3= >=1/2; <3/4, 4= >=3/4Iris: 0= normal, 1= circumcorneal redness, 2= IritisConjunctivae redness: 0=none/normal, 1= slight, 2=well-defined, 4=severe

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Max. score:

1

Reversibility:

fully reversible within: 15 days

Remarks on result:

other: Mean 1.0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

> 0 - <= 1

Max. score:

1

Reversibility:

fully reversible within: 15d

Remarks on result:

other: Mean 0.6

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

>= 2 - <= 3

Max. score:

3

Reversibility:

fully reversible within: 15d

Remarks on result:

other: Mean 2.3

Irritation parameter:

chemosis score

Remarks:

Chemosis

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Max. score:

2

Reversibility:

fully reversible within: 15d

Remarks on result:

other: Mean 0.4

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 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.

Interpretation of results:

irritating

Remarks:

Criteria used for interpretation of results: EU

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).

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

See attached justification

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Max. score:

1

Reversibility:

fully reversible within: 15 days

Remarks on result:

other: Mean 1.0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

> 0 - <= 1

Max. score:

1

Reversibility:

fully reversible within: 15d

Remarks on result:

other: Mean 0.6

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

>= 2 - <= 3

Max. score:

3

Reversibility:

fully reversible within: 15d

Remarks on result:

other: Mean 2.3

Irritation parameter:

chemosis score

Remarks:

Chemosis

Basis:

mean

Time point:

24/48/72 h

Score:

>= 0 - <= 1

Max. score:

2

Reversibility:

fully reversible within: 15d

Remarks on result:

other: Mean 0.4

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 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.

Interpretation of results:

irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

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). This result was used for read-across to tetrahydrolinalyl acetate.

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). This result was used for read-across to tetrahydrolinalyl acetate.

Reference 3

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:

other: 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.

Reason / purpose for cross-reference:

reference to same study

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(s) applied (volume or weight with unit): 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 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.

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.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Remarks on result:

other: 100% concentration

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.41

Max. score:

2

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: 100% concentration

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.18

Max. score:

4

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:

2.29

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 100% concentration

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 30% concentration

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: 30% concentration

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 30% concentration

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.28

Max. score:

3

Remarks on result:

other: 30% concentration

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 10% concentration

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: 10% concentration

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 10% concentration

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: 10% concentration

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 3% concentration

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: 3% concentration

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 3% concentration

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

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:

other: Category 2 (irritating)

Remarks:

based on CLP criteria

Conclusions:

Under the conditions 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.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

See attached justification

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Remarks on result:

other: 100% concentration

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.41

Max. score:

2

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: 100% concentration

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.18

Max. score:

4

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:

2.29

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 100% concentration

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 30% concentration

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: 30% concentration

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 30% concentration

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.28

Max. score:

3

Remarks on result:

other: 30% concentration

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 10% concentration

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: 10% concentration

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 10% concentration

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: 10% concentration

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 3% concentration

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: 3% concentration

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 3% concentration

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

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:

other: Category 2 (irritating)

Remarks:

based on CLP 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. This result was used for read-across to tetrahydrolinalyl acetate.

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. This result was used for read-across to tetrahydrolinalyl acetate.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Two studies were available, which were used in a weight of evidence approach. The first study (Chubb, 1996) is a skin irritation study performed according to OECD TG 404 and in compliance with GLP. Three New Zealand white rabbits were exposed to the undiluted test substance for 4 hours under semi-oclusive conditions. Erythema and oedema were scored 1, 24, 48, and 72 hours and 7 and 14 days after exposure. Within one hour of patch removal, well defined erythema and slight or moderate oedema were apparent at the treated site on all 3 rabbits. Slight or well defined erythema and slight oedema persisted in all animals 24 and 48 hours after patch removal and there was no decrease in the intensity of irritation at the 72 hour examination. The substance was found to cause slight to moderate irritation in the animals tested, but the mean erythema and edema scores do not exceed the limits as specified in CLP. Effects observed up until the 7 days observation period are not considered to be part of a persisting inflammatory response. Therefore the substance was considered to be not irritating. The other available study (ECETOC, 1995) was performed according to a method similar to OECD TG 404 with the read-across substance Linalool. A single 4-hour-exposure of Linalool (100% concentration) under semi-occlusive conditions in three independent experiments caused slight irritation on rabbit skin. Although mean erythema and edema scores in the animals in each test were not above 2.3 for the timepoints concerned for classification, some effects did not disappear within the 7 days observation period. Based on these persisting effects, the substance is considered to be irritating to skin and this result is used for read-across to tetrahydrolinalyl acetate. Taking the two test results together the evidence suggests that tetrahydrolinalyl acetate does not need to be considered irritating to skin, as data for the substance itself is considered to prevail over read-across data.

Eye irritation

Two comparable studies are available for the read-across substance linalool, which are used in a weight of evidence approach. The first study (Julou, 1974) is performed in accordance with a method similar to OECD 405. The eyes of six rabbits were exposed to concentrations of 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. These effects were fully reversible within 7 days. 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 can be considered as an eye irritant (100% concentration). In the other study (BASF, 1988) the primary eye irritation potential of Linalool was investigated according to a method similar to OECD TG 405. The test item was applied to the left eye of each of three young adult Vienna White rabbits 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 15 days after treatment. 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, but the substance is considered to be an eye irritant. Taking together the results of the two available studies, tetrahydrolinalyl acetate should be considered an eye irritant.

Justification for classification or non-classification

Based on the available data for skin irritation, tetrahydrolinalyl acetate does not need to be classified for skin irritation in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Based on the available data for eye irritation, tetrahydrolinalyl acetate needs to be classified as eye irritant (Category 2 / H319) in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).