p-mentha-1,4(8)-diene

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 -14 November 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline No 405 with deviations: no data on purity; no certificate of analysis of the test substance; non-ocular local and systemic adverse effects were not followed.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no data on purity; no certificate of analysis of the test substance; non-ocular local and systemic adverse effects were not followed

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

p-mentha-1,4(8)-diene

EC Number:

209-578-0

EC Name:

p-mentha-1,4(8)-diene

Cas Number:

586-62-9

Molecular formula:

C10H16

IUPAC Name:

4-isopropylidene-1-methylcyclohexene

Details on test material:

Name of the test item (as cited in the study report): HR 00/660425
Chemical name: 1-methyl-4-(1-methylethyliden)-1-cyclohexen
Batch No.: 290600015
Colour: colourless to yellowish
Storage Conditions: in a cool and dry place
Expiry Date: 31 January 2000

Test animals / tissue source

Species:

rabbit

Strain:

other: SPF albino rabbits of the stock New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
Source: Charles River, Deutschland GmbH, Kißlegg, GERMANY
Weight: 2.0-2.1 kg
Housing: Housed individually in PPO cages with perforated floor
Diet: Pelleted complete rabbit diet "Altromin 2123" (Altromin, Lage, Germany), ad libitum
Water: Domestic quality drinking water (acidified with hydrochloric acid to pH 2.5), ad libitum
Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
Temperature: 20 ± 3 °C
Humidity: 55 ± 15 %
Air changes: 10/h
Photoperiod: 12 h dark / 12 h light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
Amount(s) applied (volume or weight with unit): 0.1 mL
Concentration (if solution): undiluted

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

4 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
Washing: after the first 24 h reading fluorescein was instilled. After rinsing with 20 mL 0.9 % sodium chloride solution, the eyes were examined again using UV -light to detect possible corneal damage.

SCORING SYSTEM: According to OECD Guideline 405

TOOL USED TO ASSESS SCORE: Eyes of the animals were examined with a hand held inspection lamp fitted with white and UV -light and magnifying glass with 2 X magnifications. The examination was performed before and after instillation of fluorescein.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

other: 24, 48 and 72 h

Score:

0.1

Max. score:

2

Reversibility:

fully reversible within: 48 h

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

all animals

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

other: 24, 48 and 72 h

Score:

0.8

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

At 1 h after application, all animals showed an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible and an obvious swelling with partial eversion of lids.

At 24 h after application, one animal showed a diffuse, crimson red conjunctiva with individual vessels not easily discernible and a swelling above normal. Two animals showed some conjunctival vessels definitely injected and a swelling above normal. One animal showed an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, some conjunctival vessels definitely injected and a swelling above normal.

At 48 h after application, two animals showed some conjunctival vessels definitely injected and a swelling above normal. In one animal the conjunctiva was swollen above normal and the remaining animal was free of any signs of eye irritation.

At 72 h after application, two animals showed some conjunctival vessels definitely injected and a swelling above normal. The remaining two animals were free of any signs of eye irritation.

All the signs were resolved within 7 days after treatment.

Other effects:

no data

Any other information on results incl. tables

Table 7.3.2/1: Scores for ocular lesions

Rabbit No. /weight (kg)	Region of eye	Scores
		1 h	24 h	48 h	72 h	Day 7	Mean#
1970 / 2.1	Cornea	0	0	0	0	0	0.00
	Iris	1	0	0	0	0	0.00
	Conjunctiva: redness	2	2	1	1	0	1.33
	Conjunctiva: chemosis	2	1	1	1	0	1.00
1983 / 2.1	Cornea	0	0	0	0	-	0.00
	Iris	1	0	0	0	-	0.00
	Conjunctiva: redness	2	1	0	0	-	0.33
	Conjunctiva: chemosis	2	1	0	0	-	0.33
1986 / 2.0	Cornea	0	0	0	0	-	0.00
	Iris	1	1	0	0	-	0.33
	Conjunctiva: redness	2	1	0	0	-	0.33
	Conjunctiva: chemosis	2	1	1	0	-	0.67
1977 / 2.0	Cornea	0	0	0	0	0	0.00
	Iris	1	0	0	0	0	0.00
	Conjunctiva: redness	2	1	1	1	0	1.00
	Conjunctiva: chemosis	2	1	1	1	0	1.00

 

#: Mean scores of 24, 48 and 72 h

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The mean scores obtained with terpinolene monoconstituent at 24, 48 and 72 h were 0.0 for cornea, 0.1 for iris, 0.7 for conjunctivae and 0.8 for chemosis, therefore terpinolene monoconstituent is not classified as irritating to the eyes according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.

Executive summary:

In an eye irritation study conducted according to OECD Guideline No 405 and in compliance with GLP, 4 female SPF albino rabbits of the stock New Zealand White were exposed to 0.1 mL of undiluted terpinolene monocontituent in one eye, while other eye remained untreated and served as control. The eyelids were then gently held together for one second before releasing. At 24 h after treatment, fluorescein solution was instilled into the eyes, washed with 0.9 % sodium chloride solution and then eyes were examined using UV-light to detect possible corneal damage. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and 7 days after treatment and graded according to the method of OECD Guideline No 405.

At 1 h after instillation, all animals showed an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, a diffuse, crimson red conjunctiva with individual vessels not easily discernible and an obvious swelling with partial eversion of lids. At 24 h after application, one animal showed a diffuse, crimson red conjunctiva with individual vessels not easily discernible and a swelling above normal. Two animals showed some conjunctival vessels definitely injected and a swelling above normal. One animal showed an iris with markedly deepened folds, congestion, swelling, moderate circumcorneal injection and existence of reaction to light, some conjunctival vessels definitely injected and a swelling above normal. At 48 h after application, two animals showed some conjunctival vessels definitely injected and a swelling above normal. In one animal the conjunctiva was swollen above normal and the remaining animal was free of any signs of eye irritation. At 72 h after application, two animals showed some conjunctival vessels definitely injected and a swelling above normal. The remaining two animals were free of any signs of eye irritation. All the signs were resolved within 7 days after treatment. The calculated mean scores for each individual lesions for all animals within three scoring times (24, 48 and 72 h) were as follows: 0.0 for cornea score; 0.1 for iris score; 0.7 for conjunctivae score and 0.8 for chemosis score.

Therefore, terpinolene monoconstituent is not classified as irritating to the eyes according to Directive 67/548/EEC and CLP Regulation (EC) No 1272/2008.