Ocimum basilicum, ext.

Endpoint summary

Description of key information

Skin irritation using read across from Linalool (OECD TG 404): irritating

Eye irritation using read across from Linalool (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:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other:

Remarks:

Information is derived from read across

Justification for type of information:

The read across justification is presented in the irritation / corrosion endpoint summary and the accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

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:

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 1

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within:

Remarks on result:

other:

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:

other: 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:

other: Test 1

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:

other: 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:

other: 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:

other: 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:

other: 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:

other: 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:

other: 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:

Remarks on result:

other: 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:

other: Test 2

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:

other: Test 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 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:

other: 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:

other: 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:

other: Test 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 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:

other: 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:

other: Test 3

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Test 3

Interpretation of results:

other: Skin irritant (Category 2)

Remarks:

accordance with EU CLP (EC 1272/2008 and its updates)

Conclusions:

Under the test conditions (OECD TG 404 and GLP), the substance is considered to be a skin irritant.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Data was obtained from studies performed between 1981 and 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

study acquired from reliable secondary source therefore no detailed documentation.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

not specified

Remarks:

Albino

Details on test animals or test system and environmental conditions:

Not specified.

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Remarks:

Intact skin

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 animals
Test 2: 4 animals
Test 3: 4 animals

Details on study design:

Multi patch studies were selected for this publication because the multi-patch studies were assumed not to contravene with OECD Test Guideline 404. Additionally, no interference was reported between reactions on different patch sites in the multi-patch studies.

TEST SITE
- Area of exposure: Flank
- % coverage: Not specified
- Type of wrap if used: Semi-occlusive patches (multi-patch)

OBSERVATION TIME POINTS
After 1, 24, 48, 72h and 7 days.

SCORING SYSTEM: according to Draize (adopted by OECD TG 404)

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:

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 1

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within:

Remarks on result:

other:

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:

other: 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:

other: Test 1

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:

other: 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:

other: 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:

other: 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:

other: 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:

other: 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:

other: 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:

Remarks on result:

other: 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:

other: Test 2

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:

other: Test 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 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:

other: 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:

other: 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:

other: Test 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: 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:

other: 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:

other: Test 3

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Test 3

Irritant / corrosive response data:

Desquamation from skin surface appeared as follows:
Test 1: at day 2 (1 animal), 3 (1 animal marked) and 7 (1 animal marked)
Test 2: at day 1 (1 animal slight), 2 (1 animal slight), 3 (1 animal slight),and 7 (2 animals marked, 1 animal slight)
Test 3: at day 3 (1 animal slight) and 7 (1 animal marked, 3 animals slight)

Interpretation of results:

other: Skin irritant (Category 2)

Remarks:

accordance with EU CLP (EC 1272/2008 and its updates)

Conclusions:

Under the test conditions (OECD TG 404 and GLP), the substance is considered to be a skin irritant.

Executive summary:

The skin irritation potential of Linalool has been tested according to OECD TG 404. Two multi patch test were performed with 4 rabbits each and one single patch test was performed with 3 rabbits. All studies were performed with 0.5 mL undiluted test substance applied on the flank for 4 hours under semi-oclussive conditions. The animals were observed for 7 days after exposure and skin irritation was scored according to the Draize scoring system. Under the conditions of the test the substance was found to be skin irritating.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other:

Remarks:

Information is derived from read across

Justification for type of information:

The read across justification is presented in the irritation / corrosion endpoint summary and the accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

GLP compliance:

no

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0.6

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0.4

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Interpretation of results:

other: Eye irritant (Category 2)

Remarks:

in accordance with EU CLP (EC 1272/2008 and its updates)

Conclusions:

Under the conditions of this study, Linalool is considered to be irritating to the rabbit eye.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8 August 1988 - 28 September 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Pre-GLP, study based on OECD guideline 405 (1981)

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Savo. Med. Verzichstierzuchten GMBH
- Housing: The animals were housed in fully airconditioned rooms.
- Diet (e.g. ad libitum): 130 g per animal per day, Kliba 341, 4mm
- Water (e.g. ad libitum): approximately 250 ml per animal per day
- Acclimation period: At least 8 days before the start of the study.
- Temperature (°C): 20- 24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml per animal

Duration of treatment / exposure:

Single application

Observation period (in vivo):

15 days

Number of animals or in vitro replicates:

2 males, 1 female

Details on study design:

The substance was applied to the conjunctival sac of the right eyelid.

REMOVAL OF TEST SUBSTANCE
- Washing: 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:

cornea opacity score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0.6

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

0.4

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 15 days

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

female

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

Loss of corneal tissue was observed, but was found to be reversible. In addition pupil contraction, loss of hair at margins of eyelids, marginal vascularization of the cornea and small retractions in the eyelids were observed.

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

Interpretation of results:

other: Eye irritant (Category 2)

Remarks:

in accordance with EU CLP (EC 1272/2008 and its updates)

Conclusions:

Under the conditions of this study, Linalool is considered to be irritating to the rabbit eye.

Executive summary:

An eye irritation study was performed for Linalool, based on OECD guideline 405 and pre-GLP (Klimisch 2). 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 application of the test item. The mean score was calculated across 3 scoring times (24/48 /72 hours after instillation). 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 were reversible and were no longer evident 15 days after treatment (in 1 animal retractions of eyelids and loss of hair at margins of eyelids were still present). Based on the results obtained in the present study the test substance is considered irritant but not corrosive damage to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

The potential for skin and eye irritation for Basil oil was assessed by using read across from Linalool (CAS No.: 78-70-6). First the experimental skin and eye irritation information for Linalool will be summarised. Thereafter the read across jusitifcation is presented. The accompanying files are attached in the present endpoint summary.

 

Skin irritation in vivo (Linalool)

The skin irritation potential of Linalool has been tested according to OECD TG 404. Two multi patch test were performed with 4 rabbits each and one single patch test was performed with 3 rabbits. All studies were performed with 0.5 mL undiluted test substance applied on the flank for 4 hours under semi-oclussive conditions. The animals were observed for 7 days after exposure and skin irritation was scored according to the Draize scoring system. Under the conditions of the test the substance was found to be skin irritating.

 

Eye irritation in vivo (Linalool)

An eye irritation study was performed for Linalool, based on OECD guideline 405 and pre-GLP (Klimisch 2). 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 application of the test item. The mean score was calculated across 3 scoring times (24/48 /72 hours after instillation). 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 were reversible and were no longer evident 15 days after treatment (in 1 animal retractions of eyelids and loss of hair at margins of eyelids were still present). Based on the results obtained in the present study the test substance is considered irritant but not corrosive damage to the rabbit eye.

 

Read across justification

Basil oil obtained from the stems and leaves of Ocimum basilicum by steam distillation (Basil oil linalool type) CAS no: 84775-71-3 (target) and its skin and eye irritating properties using read across from Linalool, CAS no: 78-70-6 (source)

Introduction and hypothesis for the substance-based read across approach

Basil oil - Linalool type is a UVCB which consists of hydrocarbon constituents some of which include oxygen. Its major constituents are Linalool(contains a tertiary OH group and two C=C bonds)and Eucalyptol(contains a cyclic ether group. The full composition is given at the end of the document in the data matrix. For Basil oil - Linalool type (target) no skin and eye irritation data are available. Therefore additional information is used in accordance with Article 13 of REACH where it is said that lacking information can be generated whenever possible by applying alternative methods such SARs, grouping and read-across. For assessing the skin and eye irritation of Basil oil - Linalool type, the irritation data of Linalool are used, which is the main constituent of Basil oil - Linalool type.

Hypothesis:Basil oil - Linalool type(target)is expected to have similar skin and eye irritating properties as Linalool (source).

Available skin information:The source substance Linalool has been tested in a well performedOECDTG 404 study. The test substance was applied undiluted to intact rabbit skin under semi-occlusive conditions. Three independent experiments were performed, and the skin irritation was scored according to the Draize scoring system. Mean erythema values at 24/48/72 hours for test 1, 2 and 3 were determined to be 1.9, 2 and 1.7 (individual values are all ≤2). The mean oedema values at 24/48/72 hours for test 1, 2 and 3 were determined to be 1.4, 1.4 and 0.4 (individual values are all ≤2). Erythema was not fully reversible after 7 days. In addition desquamation was also noted. Based on these data the test substance was considered irritating to the rabbit skin.

Available eye information

The source substance Linalool (CAS 78-70-6) has been tested in anOECDTG 405 study, pre-GLP (Klimisch 2). 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 application of the test item. The mean score was calculated across 3 scoring times (24/48 /72 hours after instillation). 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 were reversible and were no longer evident 15d after treatment (in 1 animal retractions of eyelids and loss of hair at margins of eyelids were still present). Based on the results obtained in the present study the test substance is considered irritant but not corrosive damage to the rabbit eye.

Target and Source chemical(s): The information onBasil oil - Linalool type(target)and the information from Linalool (source) are presented in the Data matrix 1. This includes chemical structure of source,physico-chemical properties and toxicological information, relevant for skin and eye irritation.

Purity / Impurities:

The impurities are not relevant forBasil oil linalool type(target) as it is a UVCB (Naturally Complex Substance), the Linalool content is >45 and < 62 %.

Analogue justification

According to REACH Annex XI an analogue approach and structural alert information can be used to replace testing when information from different sources provides sufficient evidence to conclude that this substance has or does not have a particular dangerous property. The result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation.

Analogue selection:

Linaloolwas selected as analogue source because Basil oil – Linalool type consist of at least 45% Linalool.

Structural similarities and differences:Basil oil linalool type (target) contains mostly Linalool. Linalool has a tertiary alcohol, a terminal double bond and a terminal isopropene group. Such (functional) groups are also present in the other constituents: Alpha-bergamotene(contains two C=C double bonds), Germacrene D (contains three C=C double bonds), Gamma-cadinene (contains two C=C double bonds), Alpha-cadinol (contains a C=C bond and a tertiary OH group), Beta-elemene (contains three C=C double bonds), Alpha-bulnesene (contains two C=C double bonds), , Myrcene (contains three C=C double bonds) and Gamma elemene (contains three C=C double bonds). Two constituents have other functional groups: Eugenol (contains C=C double bonds (aromatic and aliphatic), an alcohol and ether group) and Estragole (contains C=C double bonds (aromatic and aliphatic), and an ether group). 

Bioavailability:All constituent of Basil oil – Linalool type have similar molecular weights and on this basis a similar bioavailability. The log Kows of the constituents have a somewhat wider range: 2.4 to 5.6. The constituents with log Kow > 4 will be somewhat less penetrating the skin and eye membranes and possibly of a lower irritation potential. These higher log Kow constituents will therefore not be more conservative.

Reactivity: For skin and eye irritation reactivity of the parent is the key property. The constituents of Basil oil – Linolool type are expected to have a similar reactive potential based on the (functional) groups present. There are no corrosion indicators such as acidic or base groups. Linalool has skin and eye irritating properties and therefore Basil – oil Linalool type has skin and eye irritating properties.

Remaining uncertainties: For some constituents (Eucayptol and Estragole) skin and eye information is present indicating the same irritation potential as Linalool and therefore skin and eye irritation properties of Linalool present the irritation potential of Basil oil – Linalool type.

Conclusions for skin and eye irritation

For Basil oil -Linalool type skin and eye irritation information is not available. This substance contains mainly Linalool and therefore the skin and eye irritation effects of Linalool derived from OECD TG 404 and 405 studies) can be used to assess these. The other constituent do not have structural features that indicate a more severe classification. Linalool is a skin and eye irritant Cat 2 and therefore the target substance Basil oil - Linalool type will similarly classified.

Final hazard conclusion: Basil oil – Linalool type is a skin and eye irritant Cat 2.

Data matrix 1. Basil oil – Linalool type (target) and Linalool (source) information to support the read across for skin and eye irritation

CHEMICAL NAME	Basil oil linalool type	Linalool*
Molecular structure	N/A
	Target	Source
CAS	84775-71-3	78-70-6
REACH registration	To be registered (Annex VII)	REACH registration
EINECS	283-900-8	201-134-4
Molecular formula	N/A	C10H18O
Molecular weight	Around 150	154.253 g/mol
Physico-chemical properties
Appearance	Clear liquid (IFF, 2017)	Clear liquid
Melting point (˚C)	<-20(IFF, 2017)	>-74
Vapour pressure (Pa)	29.1 (IFF, 2017)	27
Exp. Water solubility (mg/l)	940.5 (IFF, 2017)	1560
Exp. Log Kow	2.4-5.6 (IFF, 2017)	2.9
Human health
Skin irritation	Read Across	Skin Irrit. Cat. 2(OECD TG 404)
Eye irritation	Read Across	Eye Irrit. Cat. 2(OECD TG 405)

* Hazard properties from ECHA disseminated dossier (accessed March 2018)

 

Data matrix 2. Composition of Basil oil – Linalool typeand skin and eye information available for these constituents

NAME	CAS	Basil oil – Linalool type		Skin irritation*	Eye irritation*
		Minimum	Maximum
Linalool	126-91-0 / 78-7--6	45.00%	62.00%	Skin Irrit. Cat. 2	Eye Irrit. Cat. 2
Eucalyptol	470-82-6	3.00%	12.00%	Skin Irrit. Cat. 2	Eye Irrit. Cat. 2
Alpha-bergamotene	17699-05-7	0.01%	8.00%	Not available	Not available
Eugenol	97-53-0	0.01%	8.00%	Skin Irrit. Cat. 2	Eye Irrit. Cat. 2
Germacrene D	37839-63-7	1.00%	5.00%	Not skin irritant	Not eye irritant
Gamma-cadinene	39029-41-9	1.00%	5.00%	Not available	Not available
Alpha-cadinol	481-34-5	0.50%	5.00%	Not available	Not available
Beta-elemene	33880-83-0	0.50%	5.00%	Not available	Not available
Alpha-bulnesene	3691-11-0	0.10%	3.00%	Not available	Not available
Estragole	140-67-0	< 0.01%	3.00%	Skin Irrit. Cat. 2	Not eye irritant
Myrcene	123-35-3	< 0.01%	2.00%	Not available	Not available
Gamma elemene	3242-08-8	< 0.01%	2.00%	Not available	Not available
Other minor and unknown constituents	N/A	5.00%	20.00%
Unknown

*Skin and eye irritation information is derived from C&L inventory or ECHA disseminated dossier (accessed March 2018)

Justification for classification or non-classification

Based on the available data, the substance needs to be classified for skin irritation (Skin Irrit. 2 / H315) and eye irritation (Eye Irrit. 2 / H319) in accordance with the criteria outlined in EU CLP (EC no 1272/2008 and its amendments).