Levomenol

Endpoint summary

Description of key information

Based on the results of an OECD 404 study the test item is not requiring classification for skin irritation (UN GHS: No Category) (reference 7.3.1 -1).

Based on the results of an OECD 405 study the test item is not requiring classification for eye irritation (UN GHS: No Category) (reference 7.3.2 -1).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 October 1988 - 02 March 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Animal Breeder: Gaukler; D-6050 Offenfach/ Main, FRG
- Weight at study initiation: male 2.84 kg, females 3.0 kg
- Housing: individually in stainless steel cages with wire mesh walk floors (floor area: 40 x 51 cm).
- Diet: Kilba 341, 4 MM (Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland); about 130 g/animal/day
- Water: tap water; about 250 mL/animal/day
- Acclimation period: at least 8 days before study start (same housing conditions as during the study).

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30 - 70%
- Photoperiod (dark / light): 12 h /12 h

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

no vehicle

Controls:

other: untreated skin of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied. 0.5 mL (to test patches, 2.5 x 2.5 cm)

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3 (2 females, 1 male)

Details on study design:

TEST SITE
- Area of exposure: upper third of the back or flanks
- Type of wrap: porous dressing (four layers of absorbent gauze + porous bandage)

REMOVAL OF TEST SUBSTANCE
- Washing: Removal of the test substance at the end of the exposure period with Lutrol and Lutrol/water (1:1).
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
30 - 60 minutes after removal of the test patch and 24 h, 48 h, 72 h and 7 d after beginning of application

SCORING SYSTEM
Evaluation of erythema (R) and edema (ED):
0 = none
1 = very slight
2 = well-defined
3 = moderate to severe
4= sevree to very severe
Calculation of the mean according to 83/467/EEC criteria of 29th 1983 (for calculation of the means of erythrema and eodema only the readings of 24, 48 and 72 hours are used).

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: only one animal showed a slight edema after 24 h

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

4

Table 1: Results

Readings	Animal	Erythema	Edema	Further findings
4h	1	1	0
	2	1	0
	3	1	0
24h	1	2	0
	2	1	0
	3	2	1
48h	1	1	0
	2	0	0
	3	2	0
72h	1	0	0	scaling
	2	0	0
	3	1	0	scaling
7d	1	0	0	scaling
	2	0	0	scaling
	3	0	0	scaling
Mean (24h-72h)	1	1,0	0,0
	2	0,3	0,0
	3	1,7	0,3
Mean (24h-72h)	all animals	1,0	0,1

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions chosen, the test substance is considered not to be irritating to the skin.

Executive summary:

A study according to OECD guideline 404 was designed to assess the skin irritation potential of the test item following a single dermal application to rabbits. Three rabbits each were administered a single dermal dose of 0.5 mL of the test substance and observed for 7 days. Slight erythrema were observed, which were fully rerversible within 7 days. One animal showed a very slight edema which was fully reversible within 48 hours. The mean erythrema and oedema scores were below the threshold for classification. The test substance is considered not to be irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 October 1988 - 02 March 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Animal Breeder: Gaukler, D-6050 Offenbach/Main, FRG
- Mean weight at study initiation: males 3.59 kg, female 3.57 kg
- Housing: Idividually in stainless steel cages with wire mesh walk floors (floor area: 40 x 51 cm).
- Diet: about 130 g per animal per day of Kliba 341, 4 MM (Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland)
- Water: about 250 mL tap water per animal per day
- Acclimation period: at least 8 days before study start (same housing conditions as during the study)

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30 - 70%
- Photoperiod (dark / light): 12 h / 12 h

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

72 hours (substance was not washed out)

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 (two males, one female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The test substance was not washed out.

SCORING SYSTEM: According to OECD guideline OECD 405
- Readings: 1 h, 24 h, 48 h, 72 h after application

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

1.2

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Table 1: Results

		Cornea	Iris	Conjunctiva
Readings	Animal	Opacity		Redness	Swelling	Further findings
1h	1	0	0	2	0
	2	0	0	2	0
	3	0	0	2	0
24h	1	0	0	2	0
	2	0	0	2	0
	3	0	0	2	0
48h	1	0	0	1	0
	2	0	0	2	0
	3	0	0	2	0
72h	1	0	0	0	0
	2	0	0	0	0
	3	0	0	0	0
Mean (24h-72h)	1	0.0	0.0	1.0	0.0
	2	0.0	0.0	1.3	0.0
	3	0.0	0.0	1.3	0.0
Mean (24h-72h)	all animals	0.0	0.0	1.2	0.0

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions chosen, the test substance is considered not to be irritating to the eye.

Executive summary:

A study according to OECD guideline 405 was designed to assess the eye irritation potential of the test item. 0.1 mL of test substance were applied undiluted to the conjunctival sac of the right eyelid of 3 rabbits. The untreated eyes of the same animals served as control. The substance was not washed out and the reaction to the eyes was observed 1, 24, 48 and 72 hours after application. Mean erythrema, edama and chemosis scores at 24/48/72 h were 0.0 and the mean conjunctivae score was 1.2. This observed effect was reversible within 72 hours. The test substance is considered not to be irritating to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

OECD 404 (reference 7.3.1-1)

A study according to OECD guideline 404 was designed to assess the skin irritation potential of the test item following a single dermal application to rabbits. Three rabbits were each administered a single dermal dose of 0.5 mL of the test substance and observed for 7 days. Slight erythrema were observed, which were fully rerversible within 7 days. One animal showed a very slight edema which was fully reversible within 48 hours. The mean erythrema and oedema scores were below the threshold for classification. The test substance is considered not to be irritating to the skin.

Pretest for OECD 406 (reference 7.4.1 -1)

As a pretest for a sensitisation study (Buehler Test) in accordance with OECD Guideline 406 the skin irritation potential of the (+/-)-α-Bisabolol (source substance) was assed using 7 female guinea pigs. The test item was tested undiluted and diluted (concentration: 25%, 50% and 75%). Lutrol E 400 DAB was used as vehicle. Patches containing 0.5 mL of the test substance or test substance formulations were applied to the skin of the flanks under an occlusive dressing. The exposure duration was 6 hours. 6 hours and 30 hours after beginning of the application the skin reaction was scored. Only one animal showed discrete or patchy erythema after application of the diluted test item (75%). All other animals showed no visible changes. Therefore, the test substance is considered not to be irritating to the skin.

(+/-)-α-Bisabolol (source substance) is considered to be a suitable read across substance for (-)-α-Bisabolol (target substance).

Eye irritation

OECD 405 (reference 7.3.2-1)

A study according to OECD guideline 405 was designed to assess the eye irritation potential of the test item. 0.1 mL of test substance were applied undiluted to the conjunctival sac of the right eyelid of 3 rabbits. The untreated eyes of the same animals served as control. The substance was not washed out and the reaction to the eyes was observed 1, 24, 48 and 72 hours after application. Mean erythrema, edama and chemosis scores at 24/48/72 h were 0.0 and the mean conjunctivae score was 1.2. This observed effect was reversible within 72 hours. The test substance is considered not to be irritating to the eye.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on this data, the substance is not considered to be classified for skin irritation and eye damaging potential under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.