2,4-dimethyl-4-phenyltetrahydrofuran

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Techniques published by the FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) and Draize and Kelley (Drug. Cosmet. Industr. 71 (1952) 36) are followed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Deviations to the OECD guideline 405: No 1 hour and 14-day observation period and 6 animals used instead of 3

Principles of method if other than guideline:

Techniques published by the FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) and Draize and Kelley (Drug. Cosmet. Industr. 71 (1952) 36) are followed.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

rel-(2R,4R)-2,4-dimethyl-4-phenyltetrahydrofuran

Cas Number:

99343-90-5

Molecular formula:

C12H16O

IUPAC Name:

rel-(2R,4R)-2,4-dimethyl-4-phenyltetrahydrofuran

Constituent 2

Reference substance name:

rel-(2S,4R)-2,4-dimethyl-4-phenyltetrahydrofuran

Cas Number:

99343-91-6

Molecular formula:

C12H16O

IUPAC Name:

rel-(2S,4R)-2,4-dimethyl-4-phenyltetrahydrofuran

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Not reported

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

After administration, the upper and lower eye lid were carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material.

Observation period (in vivo):

24, 48, 72 hours and 7 days after the instillation.

Number of animals or in vitro replicates:

6

Details on study design:

Six New Zealand White albino rabbits are used for each test substance. The animals are caged individually and receive no hay or other extraneous material that might enter the eyes.
The eyes of the animals are examined before testing and only those animals without observable eye defects are used. One tenth of a milliliter of the test substance is allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye, remaining untreated, serves as a control.
The eyes are not washed following instillation and the animals are released immediately.
The eyes are examined at 24, 48, 72 hours and 7 days after instillation of the test material.
An animal is considered as giving a positive reaction if there is, at any of the readings, discernible opacity of the cornea (other than a slight dulling of the normal lustre), or ulceration of the cornea, or inflammation of the iris (other than a slight deepening of the folds (rugae) or a slight circumcorneal injection), or if such substance produces in the conjunctivae (palpebral and bulbar, excluding the cornea and iris) an obvious swelling with partial eversion of the lids, or a diffuse deep-crimson red with individual vessels not easily discernible. The FDA-scoring is used.
The test is considered positive if four or more of the animals in the test group of six rabbits exhibit a positive reaction. If one animal exhibits a positive reaction, the test is regarded as negative.
If two or three animals exhibit a positive reaction, the test is repeated, using a different group of six animals. The second test is considered as positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the second test exhibit a positive reaction, the test is again repeated with a different group of six animals. Should a third test be needed, the substance will be regarded as an irritant if two or more animals exhibit a positive response.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal: #11 and #12

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 2

Irritation parameter:

chemosis score

Basis:

animal: #10

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 3

Irritation parameter:

chemosis score

Basis:

animal: #9

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal: #7 and #8

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal: #12

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal: #11

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal: #10

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal: #9

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal: #7 and #8

Time point:

24/48/72 h

Score:

1.6

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Results 10

Irritation parameter:

iris score

Basis:

animal: #11 and #12

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Results 11

Irritation parameter:

iris score

Basis:

animal: #7

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 12

Irritation parameter:

iris score

Basis:

animal: #9 and #10

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 13

Irritation parameter:

iris score

Basis:

animal: #8

Time point:

24/48/72 h

Score:

0.6

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 14

Irritation parameter:

cornea opacity score

Basis:

animal: #7 and #8

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 15

Irritation parameter:

cornea opacity score

Basis:

animal: #9, #10 and #11

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 16

Irritation parameter:

cornea opacity score

Basis:

animal: #12

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

The test product caused slight corneal opacity in three rabbits (No.7, 8 and 12), slight iritis in four rabbits (No.7, 8, 11 and 12) and slight or moderate redness and swelling of the conjunctivae in all animals. In the course of the seven-day observation period these lesions cleared up, except for slight redness of the conjucntivae, noted in two animals (No.7 and 8) at the seventh day.

Any other information on results incl. tables

Table 1: Individual Scores Awarded to the Occular Lesions Elicted by the Rhubafurane

Time point	Rabbit Number	Cornea	Iris	Conjunctivae
				Redness	swelling
After 24 hours	7	1	0	2	2
	8	1	1	2	2
	9	0	0	1	1
	10	0	0	1	1
	11	0	1	2	2
	12	1	1	2	2
After 48 hours	7	1	1	2	2
	8	1	1	2	2
	9	0	0	1	0
	10	0	0	1	1
	11	0	0	2	1
	12	1	0	1	1
After 72 hours	7	1	0	1	2
	8	1	0	1	2
	9	0	0	1	1
	10	0	0	0	0
	11	0	0	0	0
	12	0	0	1	0
After 7 days	7	0	0	1	0
	8	0	0	1	0
	9	0	0	0	0
	10	0	0	0	0
	11	0	0	0	0
	12	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test item is not classified as irritant to the eyes according to the Regulation (EC) No. 1272/2008 (CLP) and to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Executive summary:

In an eye irritation study performed according to an equivalent study following the OECD Guideline No. 405 protocol, New Zealand White albino rabbits are used for assess the eye irritant potential of the test material. 

0.1 mL of undiluted test item was instilled into the right eye of 6 rabbits. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test item, and then released. The left eye remained untreated and served as control. The eyes were examined and the changes were observed at 24, 48, 72 h and 7 days after instillation of test item and graded according to the Draize method.
The eyes are not washed following instillation and the animals are released immediately

The test product caused slight corneal opacity in three rabbits (No.7, 8 and 12), slight iritis in four rabbits (No.7, 8, 11 and 12) and slight or moderate redness and swelling of the conjunctivae in all animals. In the course of the seven-day observation period these lesions cleared up, except for slight redness of the conjucntivae, noted in two animals (No.7 and 8) at the seventh day.

Mean individual scores at 24, 48 and 72 h after exposure for the 6 animals were 1 / 1 / 0 / 0 / 0 / 0.6 for cornea score; 0.3/ 0.6 / 0 / 0 / 0.3 / 0.3 for iris score; 1.6 / 1.6 / 1 / 0.6 / 1.3 / 1.3 for conjunctivae score and 2 / 2 / 0.6 / 0.6 / 1 / 1 for chemosis score.

Under the test conditions, the test item is not classified as irritant to the eyes according to the Regulation (EC) No. 1272/2008 (CLP) and to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).