L-p-mentha-1(6),8-dien-2-one

Endpoint summary

Description of key information

Serious eye damage/eye irritation: not irritating (OECD 405/ EEC Guideline B.5, GLP)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)

Endpoint conclusion

Endpoint conclusion:

no study available

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:

06-09-1999 to 10-09-1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: OECD Guideline No. 405 (Acute Eye Irritation/Corrosion) and EEC Guideline Method B.5

GLP compliance:

yes

Species:

rabbit

Strain:

other: New Zealand White (SPF albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kißleg, Germany
- Weight at study initiation: 1.7 - 2.0 kg
- Housing: Caged individually in PPO cages (floor area: 2576 cm2) with perforated floor.
- Diet (e.g. ad libitum): Pelleted complete rabbit diet "Altromin 2123" from Altromin, D-32791 Lage, Lippe, was available ad libitum
- Water (e.g. ad libitum): Domestic quality drinking water (acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth) ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 10 times/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

24 hrs

Observation period (in vivo):

1 hr, 24 hr, 48 hr and 72 hr.

Number of animals or in vitro replicates:

4 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Method of Draize/Grading of Ocular Lesions in OECD Guideline 405 with additions noted below in Tables 1 and 2.

TOOL USED TO ASSESS SCORE: The eyes were examined and the grade of ocular reaction was recorded 1 hr and 24 hrs later. After the first 24 hr reading, fluorescein was instilled. After rinsing with 20 ml 0.9% sodium chloride solution the eyes were examincd again using UV-light to detect possible
corneal damage.

Only the left eye was treated. The right eye remained untreated and served as control.

Irritation parameter:

cornea opacity score

Remarks:

- opacity

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Remarks:

- redness

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0.4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Individual animal data is presented below (Table 3)

Table 3: Scores for ocular lesions (all animals)

Rabbit No./ Weight per kg		1h	24h	24h	48h	72h	Individual mean score*
				F
1627 / 2.0	Cornea opacity, degree	0	0	0	0	0	0
	Cornea opacity, area	0	0	0	0	0
	Iris	1	0	-	0	0	0
	Conjunctiva:    Redness	2	1	-	0	0	0.33
	Chemosis	1	0	-	0	0	0
	Discharge	0	0	-	0	0
1628 / 1.9	Cornea opacity, degree	0	0	0	0	0	0
	Cornea opacity, area	0	0	0	0	0
	Iris	0	0	-	0	0	0
	Conjunctiva:   Redness	2	1	-	0	0	0.33
	Chemosis	1	0	-	0	0	0
	Discharge	1	0	-	0	0
1629 / 1.7	Cornea opacity, degree	0	0	0	0	0	0
	Cornea opacity, area	0	0	0	0	0
	Iris	0	0	-	0	0	0
	Conjunctiva:   Redness	2	1	-	0	0	0.33
	Chemosis	1	0	-	0	0	0
	Discharge	1	0	-	0	0
1630/ 1.8	Cornea opacity, degree	0	0	0	0	0	0
	Cornea opacity, area	0	0	0	0	0
	Iris	1	0	-	0	0	0
	Conjunctiva:    Redness	2	1	-	1	0	0.67
	Chemosis	1	0	-	0	0	0
	Discharge	0	0	-	0	0

F: Reading after instillation of Fluorescein

* Only the scores from the readings after 24, 48 and 72 hours are included in the calculation of the individual mean scores

Table 4: Summary of mean values from Table 3

	Mean Value
cornea opacity	0
iris lesion	0
redness of conjunctiva	0.4
oedema of conjunctiva (chemosis)	0

Interpretation of results:

not irritating

Conclusions:

The substance L-carvone was not irritating in the eyes of New Zealand White rabbits.

Executive summary:

In a primary eye irritation study (01628) 0.1mL of L-carvone (undiluted) was instilled into the conjunctival sac of the left eye of young adult New Zealand White (SPF albino) rabbits (4/females) for 24 hours. The eye was not washed after instillation of the test article. Animals then were observed for 1 hr, 24 hr, 48 hr and 72 hrs after dosing. Irritation was scored by the method of Draize/Table: Grading of Ocular lesions (OECD 405) with additions noted in Tables 1 and 2.

The following mean values, based on the results from the 24, 48 and 72 hour readings,were calculated - cornea opacity: 0; iris lesion: 0; oedema of conjunctiva (chemosis): 0; redness of conjunctiva: 0.4.

In this study, L-carvone is not an eye irritant based on the results of this OECD guideline/GLP study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

In accordance with Column 2 of ANNEX VIII, an in vivo skin irritation study does not need to be conducted as an acute toxicity study by the dermal route does not indicate skin irritation up to the limit dose level (2000 mg/kg bw).

 

Serious eye damage/eye irritation

An in vitro eye irritation study was not required as an in vivo study was available.

In a primary eye irritation study (OECD 404/GLP) 0.1mL of L-carvone (undiluted) was instilled into the conjunctival sac of the left eye of young adult New Zealand White (SPF albino) rabbits (4/females) for 24 hours. The eye was not washed after instillation of the test article. Animals then were observed for 1 hr, 24 hr, 48 hr and 72 hrs after dosing. Irritation was scored by the method of Draize/Table: Grading of Ocular lesions (OECD 405) with additions noted in Tables 1 and 2. The following mean values, based on the results from the 24, 48 and 72 hour readings,were calculated - cornea opacity: 0; iris lesion: 0; oedema of conjunctiva (chemosis): 0; redness of conjunctiva: 0.4. In this study, L-carvone is not an eye irritant.

The results from this study are acceptable to use in the human health risk assessment.

Justification for classification or non-classification

Based on the available information in the dossier, the substance L-carvone (CAS No. 6485-40-1) does not need to be classified for skin irritation/corrosion or serious eye damage/eye irritation when considering the criteria outlined in Annex I of 1272/2008/EC.