Reaction mass of (2R,5R)-2-isopropyl-5-methylcyclohexanone and (2S,5R)-2-isopropyl-5-methylcyclohexanone

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

other: component of reaction mass

Adequacy of study:

key study

Study period:

July-August 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: According to ECVAM ToxRTool reliability 2. GLP study performed according to OECD guideline 405 of february 1987. Deficiencies: The description of the study results is not transparent and without further information missleading.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

L-menthol

EC Number:

218-690-9

EC Name:

L-menthol

Cas Number:

2216-51-5

Molecular formula:

C10H20O

IUPAC Name:

(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexanol

Constituent 2

Reference substance name:

Cyclohexanol, 5-methyl-2-(1-methylethyl)-, [1R-(1.α.,2.β.,5.α.)]-

IUPAC Name:

Cyclohexanol, 5-methyl-2-(1-methylethyl)-, [1R-(1.α.,2.β.,5.α.)]-

Constituent 3

Reference substance name:

HR 89/620001

IUPAC Name:

HR 89/620001

Details on test material:

- Substance type: White crystalline powder (tiny crystals)
- Physical state: solid
- 64.3 % solubilised in diethyl phthalate
Substance purity : 99.7%
Expiration date of the lot : not stated

Test animals / tissue source

Species:

rabbit

Strain:

other: Chbb:HM, C.H. Boehringer, Biberach:Himalaya

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Strain: SPF albino female rabbits Chbb:HM, C.H. Boehringer, Biberach; Himalaya
- Source: Dr Karl Thomae GmbH, D-7950 Biberach an der Riss 1.
- Weight at study initiation: 2600 to 2800 g
- Housing: Single PPL cages 45x55 cm with perforated floor
- Diet (e.g. ad libitum): free access to food pellets "Altromin 2123" from Chr. Petersen Ltd, DK-4100 Ringsted
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week
- Controls: internal control (right eye)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): 6 times an hour
- Photoperiod (hrs dark / hrs light): 12 hours / 12 hours

Test system

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration 1 28.6%(W7W) L-Menthol in Dieethyl Phthalate (DEP) (in studie stated as vehicle)
- Concentration 2 :50 g L-Menthol + 50 g 28.6% (w/w) L-Menthol in DEP = 64.3% (w/w) in DEP

Duration of treatment / exposure:

No removal after application. Once applied the test material remained in contact with the eye throughout the experiment.

Observation period (in vivo):

Observation at 1 hour, 24 hours, 48 hours and 72 hours and 7 days.

Number of animals or in vitro replicates:

4 rabbits tested (female) for each concentration

Details on study design:

The day before testing both eyes of the animals were examined with an ophthalmoscope to ensure there were no eye defects or irritation. The examination was performed before and after instillation of oculoguttae flouresceini (Pb.N.),
Both the left and right eyes were treated. The right eyes with the vehicle and the left eyes with the test article solution.
About 0.1 ml of the test article concentration 1 or test article concentration 2 was placed in the left or right eye, respectively, of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped. The lids were then gently held together for about one second. The eyes were examined and the grade of ocular reaction was recorded 1 hour later. 24 hours later an examination was performed before and after instillation of oculoguttae flouresceini. After the examination the eyes were rinsed with 20 ml of a 0.9% sodium chloride solution
The eyes were also examined 48 and 72 hours after the treatment, as well as on day 7.

SCORING SYSTEM: see table below

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Time point:

other: over all time points

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: low concentration score 0.8

Results 2

Irritation parameter:

iris score

Remarks:

lesion

Basis:

mean

Time point:

other: over all time points

Score:

0

Max. score:

2

Remarks on result:

other: low concentration score 0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: over all time points

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: low concentration score 1.2

Results 4

Irritation parameter:

conjunctivae score

Remarks:

oedema

Basis:

mean

Time point:

other: over all time points

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: low concentration score 0.3

Irritant / corrosive response data:

For further details see table below

Any other information on results incl. tables

Results for left eye 64% L-Menthol:

Rabbit	Conjunctiva Discharge	Conjunctiva Redness	Conjunctiva Chemosis	Iris	Cornea	Opacity area (with fluoresceine)
#1 at 1 h	3	2	1	0	1	1
#1 at 24 h	1	2	1	0	1	4 (4)
#1 at 48 h	0	2	0	0	1	3 (3)
#1 at 72 h	0	1	0	0	1	3 (3)
#1 at 7 d	0	0	0	0	0	0
#2 at 1 h	3	2	1	0	1	2
#2 at 24 h	1	3	1	0	1	4 (4)
#2 at 48 h	0	2	0	0	1	2 (2)
#2 at 72 h	0	1	0	0	1	1 (1)
#2 at 7 d	0	0	0	0	0	0
#3 at 1 h	3	2	0	0	1	1
#3 at 24 h	1	3	2	0	1	4 (4)
#3 at 48 h	0	3	1	0	1	4 (4)
#3 at 72 h	0	2	1	0	1	3 (3)
#3 at 7 d	0	0	0	0	0	0
#4 at 1 h	3	2	1	0	1	3
#4 at 24 h	1	2	1	0	1	4 (4)
#4 at 48 h	0	2	0	0	1	3 (3)
#4 at 72 h	0	1	0	0	1	1 (1)
#4 at 7 d	0	0	0	0	0	0
24, 48 and 72 h mean	0.3	2.0	0.6	0.0	1.0

 

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Eye irritant category 2 under CLP, but does not meet eye irritant criteria under DSD. Criteria used for interpretation of results: EU

Conclusions:

Menthols causes moderate to intense reactions of rabbit eye cornea and conjunctiva, which is complete reversible within 7 days.

Executive summary:

The primary eye irritant effect of menthols was investigated using L Menthol in concentration of 29% and 64% according to the method recommended in the OECD Guideline No.405,“Acute Eye Irritation/Corrosion”, Feb. 1987.

Under the experimental conditions described in the report, moderate to intense reactions of cornea and conjunctiva were seen in all rabbits according to the used menthol concentration.  

All effects seen were fully reversible within 7 days.

 

Menthols should be classified as eye irritant category 2 under CLP but does not require classification for eye irritation/corrosion under DSD.