2-butyl-4,4,6-trimethyl-1,3-dioxane

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted in July 1981.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

other: FDA of the United. States (Fed. Reg. 28 (119), 5582, 1963)

Deviations:

not specified

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

other: Draize and Kelley (Drug Cosmet. Industr. 71 (1952) 36)

Deviations:

not specified

GLP compliance:

no

Remarks:

Study pre-dates GLP.

Test material

Test material information

Constituent 1

Reference substance name:

Herboxane

IUPAC Name:

Herboxane

Test material form:

other: liquid

Details on test material:

- Name of test material: Herboxane
- Physical state: Clear colourless liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100%

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6 animals

Details on study design:

Protocol for eye irritation test
In general the techniques of tests as 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.
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 millilitre of the test substance, or in the case of solids or semisolids, 100 milligrams of the test substance, is allowed to tell everted lower lid. of one eye of each rabbit; the War 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 2%, 1&8, 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 (rugse) or a. slight circumcorneal injection), or if such substance produces in the conjunctivae (palpebrel 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 scale was used.
The test is considered positive it 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 9, positive reaction, the test is re- pea-ted, 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 he needed, the substance will be regarded as an irritant if two or more animals exhibit a positive response.
A substance which has elicited corneal and/or iris lesions which have not cleared by the seventh day reading, is considered a severe eye irritant.

Grades for ocular lesions:
Cornea.
No ulceration or opacity = 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible = (1)'
Easily discernible translucent areas, details of iris slightly obscured = 2
Nacreous areas, no details of iris visible, size of pupil barely discernible = 3
Complete corneal opacity, iris not discernible = 4

Iris
Normal = 0
Markedly deepened folds, congestion, swelling, moderate circumcorneal injection (any of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive) = (1)*
No reaction to light, haemorrhage, gross destruction (any or all of these) = 2

Conjunctivae
-Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal = 0
Some vessels definitely injected = 1
Diffuse, crimson red, individual vessels not easily discernible = (2)*
Diffuse beefy red = 3
-Chemosis
No swelling = 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids (2)*
Swelling with lids about half closed = 3
Swelling with lids more than half closed = 4
(*Bracket figures indicate lowest grades considered positive.)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

Animal 1

Basis:

mean

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Based on conjunctival redness

Results 2

Irritation parameter:

conjunctivae score

Remarks:

Animal 2

Basis:

mean

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Based on conjunctival redness

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Animal 3

Basis:

mean

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Based on conjunctival redness

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Animal 4

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Based on conjunctival redness

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Animal 5

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Based on conjunctival redness

Results 6

Irritation parameter:

conjunctivae score

Remarks:

Animal 6

Basis:

mean

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Based on conjunctival redness

Results 7

Irritation parameter:

chemosis score

Remarks:

Animal 1

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

chemosis score

Remarks:

Animal 2

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

chemosis score

Remarks:

Animal 3

Basis:

mean

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 10

Irritation parameter:

chemosis score

Remarks:

Animal 4

Basis:

mean

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

chemosis score

Remarks:

Animal 5

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 14

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 15

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 16

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 17

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 18

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 19

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 20

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 21

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 22

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 23

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 24

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Any other information on results incl. tables

Herboxane caused slight conjunctivitis in 2/6 rabbits and moderate conjunctivitis in 4/6 rabbits. Two animals (no. 3 and 4) showed slight discharge of eye fluid. At the end of the seven—day observation period four animals still showed slight redness of the conjunctivae.

Table Of Individual Scores Awarded To The Ocular Lesions Elicited By Herboxane

Rabbit Number	Score
	Cornea	Iris	Conjunctivae
			Redness	Chemosis
after 24 hours
1	0	0	2	1
2	0	0	1	0
3	0	0	2	1
4	0	0	2	2
5	0	0	1	1
6	0	0	2	1
after 48 hours
1	0	0	1	0
2	0	0	2	1
3	0	0	1	1
4	0	0	2	2
5	0	0	1	0
6	0	0	2	0
after 72 hours
1	0	0	1	0
2	0	0	1	0
3	0	0	1	0
4	0	0	2	1
5	0	0	1	0
6	0	0	1	0
after 7 days
1	0	0	1	0
2	0	0	0	0
3	0	0	1	0
4	0	0	1	0
5	0	0	1	0
6	0	0	0	0

 

On the basis of the present results it is concluded that according to the FDA-standards undiluted Herboxane is considered to be an eye irritant.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the basis of the present results it is concluded that according to the FDA-standards undiluted Herboxane is considered to be an eye irritant.

Executive summary:

The product Herboxane was examined an in-eye irritation test. New Zealand White albino rabbits were used as the experimental animals. According to the FDA-standards, undiluted Herboxane is considered to be an eye irritant.