Cyclopropanemethanol, 1-methyl-2-[(1,2,2-trimethylbicyclo[3.1.0]hex-3-yl)methyl]-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 17 September to 25 September 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1S,2S)-, rel-

Molecular formula:

C15H26O

IUPAC Name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1S,2S)-, rel-

Constituent 2

Reference substance name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1R,2R)-, rel-

Molecular formula:

C15H26O

IUPAC Name:

Cyclopropanemethanol, 1-methyl-2-[[(1S,3R,5R)- 1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl]-, (1R,2R)-, rel-

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Javanol
- Physical state: Pale yellow viscous liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH - Birkendorferstrasse 65 - D-88397 Biberach/Riss
- Age at study initiation: 12 weeks
- Weight at study initiation:
Male: 2679 g
Female: 2940 and 2862 g
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, ad libitum
- Water (e.g. ad libitum):Community tap water from Itingen, ad libitum
- Acclimation period: four days under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-115
- Photoperiod (hrs dark / hrs light): 12

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.1 ml per animal of Javanol was applied undiluted as it was delivered by the sponsor

Duration of treatment / exposure:

On the day of treatment, the test article undiluted was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test item. The right eye remained untreated and served as a control.

Observation period (in vivo):

The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours after administration

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM:
The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours, as well as 7 days after application.

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel / Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 22

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: 23

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal: 24

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal: 22

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal: 23

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal: 24

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal: 22

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal: 23

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal: 24

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 10

Irritation parameter:

chemosis score

Basis:

animal: 22

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 11

Irritation parameter:

chemosis score

Basis:

animal: 23

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 12

Irritation parameter:

chemosis score

Basis:

animal: 24

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Irritation: Application of the test article to healthy rabbit conjunctivae resulted in a primary eye irritation score of 0.78. Slight to moderate reddening and sweling of the conjunctivae were noted in all animals after one hour. Slight to moderate reddening of the conjunctivae persisted in all animals after 24 hours and in one animal after 48 hours. Moderate watery discharge was evident in all animals, as was hyperemia of the scleral blood vessels. All findings were reversible after 72 hours.
Corrosion: No corrosion of the cornea was observed at any of the reading times.

Other effects:

Coloration: No staining of the cornea, sclera or conjunctivae by the test article was observed.
Body weights: The body weight of all rabbits were considered to be within the normal range of viariability.

Any other information on results incl. tables

Eye irritation score - individual values:

Animal number	sex	Evaluation interval	Corneal opacity	Iris	conjunctivae		cumulative
					Redness	Chemosis	Score	Mean
22 23 24	M F F	1 hour	0 0 0	0 0 0	2 2 2	1 1 1	3.00 3.00 3.00	3.00
22 23 24	M F F	24 hours	0 0 0	0 0 0	0 0 2	1 1 2	1.00 1.00 4.00	2.00
22 23 24	M F F	48 hours	0 0 0	0 0 0	0 0 1	0 0 0	0.00 0.00 1.00	0.33
22 23 24	M F F	72 hours	0 0 0	0 0 0	0 0 0	0 0 0	0.00 0.00 0.00	0.00

Eye irritation scores - mean values after 24, 48 and 72 hours:

Animal number	Sex	Cornea opacity	N	Iris	N	Conjunctivae				Primary eye irritation score
						Redness	N	Chemosis	N
22 23 24	M F F	0.00 0.00 0.00	3 3 3	0.00 0.00 0.00	3 3 3	0.00 0.00 1.00	3 3 3	0.33 0.33 0.67	3 3 3	0.78
Mean score		0.00		0.00		0.44		0.00

N = number of available data points

Eye irritation scores - assessment according to EC guidelines:

Evaluated intervals	Corneal opacity	Iris	Conjunctivae
			Redness	Chemosis
24 hours 48 hours 72 hours	Not irritating	Not irritating	Not irritating	Not irritating

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the referred classification criteria, Javanol is considered to be 'not irritating' to the rabbit eye.

Executive summary:

A key eye irritation study was performed according to OECD guideline 405 (adopted 1987), EEC Commission Directive 92/69/EEC (1992) and in compliance with GLP.

The primary eye irritation potential of the test article was investigated by instillation of 0.1 mL into one eye of each of three young adult New Zealand White rabbits. The treated eyes were not ronsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then divding the resulting total by the number of data points. The primary irritation score was 0.78 (max. 13). Reddening and/or swelling the conjunctivae were noted in all animals after 24 hours. Reddening was noted after 48 hours in one animal only. Watery discharge and hyperemia of the sclera blood vessels were seen in all animals after one hour. All findings were reversible after 72 hours.

No staining of the sclera, conjunctivae and cornea of the treated eyes by the test article was observed. No corrosion was observed at any measuring intervals. Under the conditions of the this test, Javanol is not considered to be an eye irritant.

Based upon the test results and in accordance to the Regulation (EC) No 1272/2008 (CLP) and Globally Harmonized System of Classification and Labeling of Chemicals (GHS), Javanol is not classified.