1H,3H-Naphtho[1,8-cd]pyran-6,7-dicarboxylic acid, 1,3-dioxo-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test performed before OECD and GLP guidelines. Important aspects (dosing, grading criteria) comparable with current OECD guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Federal Register Vol 38, no 187, S. 27019, 1973

Deviations:

no

GLP compliance:

no

Remarks:

pre-guideline study

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dioxo-3-oxatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene-8,10-dicarboxylic acid

EC Number:

619-817-4

Cas Number:

52671-72-4

Molecular formula:

C14H6O7

IUPAC Name:

2,4-dioxo-3-oxatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene-8,10-dicarboxylic acid

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- SPF-Albino-Himalayan
- Source: Hoechst AG, breeding colony
- Weight at study initiation: 1,5 - 2,0 kg
- Housing: single caged
- Diet: standard diet ERKA 8300, ad libitum
- Water: tap water, ad libitum

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye remained untreated and served as control respectively

Amount / concentration applied:

- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

24 h, rinsing with physiological saline 24 h after instillation

Observation period (in vivo):

examinations at 1, 7, 24, 48, 72 h after instillation

Number of animals or in vitro replicates:

6

Details on study design:

Application of the substance to the conjunctival sac of the left eye of each animal, the right eye served as control respectively

- Instillation: 100 mg of the undiluted substance

- Washing: Washing with physiological saline 24 h after administration

- Tool to assess score after 48 and 72 h: 0.01 % solution of fluorescein sodium, under UV light

The eyes are examined and the grade of ocular reaction is recorded at 1, 7, 24, 48, and 72 hours.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: # 39, 41, 42 each

Time point:

other: mean of 24, 48, 72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: 3 animals

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: # 38, 40, 43 each

Time point:

other: mean of 24, 48, 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: 3 animals

Results 3

Irritation parameter:

iris score

Basis:

animal: # 38-43 each

Time point:

other: mean of 24, 48, 72 h

Score:

0

Max. score:

2

Reversibility:

other: no signs of irritation (iris) at any time

Remarks on result:

other: all animals

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal: # 38-43 each

Time point:

other: mean of 24, 48, 72 h

Score:

2.1

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: all animals

Results 5

Irritation parameter:

chemosis score

Basis:

animal: # 38-43 each

Time point:

other: mean of 24, 48, 72 h

Score:

2.1

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

other: all animals

Irritant / corrosive response data:

discharge was observed until 48 h after administration in all animals. After end of observation period still existent for animals # 39 and 42. Effects on cornea (grade 1) were not reversible within 72 h in 3 animals . For conjunctiva chemosis and redness grade 1 or 2 was recorded for all animals after 72 h. There were no later observation points, but signs of irritation are considered to be fully reversible in the course of a prolonged observation period of 21 days.

Other effects:

no other effects reported

Any other information on results incl. tables

Animal no	Evaluation Interval	Cornea	Conjunctiva			Iris
		Opacity	Redness	Chemosis	Discharge
38	1 h	1	2	3	X	0
39		1	2	3	X	0
40		1	2	3	X	0
41		0	2	2	X	0
42		1	2	3	X	0
43		1	2	3	X	0
38	7 h	1	2	3	X	0
39		1	2	3	X	0
40		1	2	4	X	0
41		1	2	2	X	0
42		1	2	3	X	0
43		1	2	3	X	0
38	24 h	1	3	2	X	0
39		1	3	4	X	0
40		1	2	2	X	0
41		1	2	3	X	0
42		1	2	3	X	0
43		1	2	2	X	0
38	48 h	0	2	2	X	0
39		1	2	3	X	0
40		0	2	1	X	0
41		1	3	2	X	0
42		1	2	3	X	0
43		0	2	1	X	0
38	72 h	0	2	2		0
39		1	2	2	X	0
40		0	2	1		0
41		1	2	1		0
42		1	2	2	X	0
43		0	1	1		0

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

According to the classification criteria of Regulation (EC) No 1272/2008 the test item is irritating to eyes, category 2 under these test conditions.

Executive summary:

The test material was subject to an acute eye irritation/corrosion test in 6 Himalayan White rabbits according to FDA guideline. 100 mg test substance were placed into the conjunctival sac of one eye of each rabbit. Reactions were recorded frequently during the observation period of 72 h.

The test item caused grade 2.1 (mean of 24, 48, 72h) conjunctiva redness and chemosis and grade 1 (3 rabbits, mean of 24, 48, 72h) cornea opacity, which were not fully reversible within 72 h. Iris grade was 0 for all rabbits (no signs of irritation at any time). Signs of irritation were not fully reversible within the observation period of 72 h, but are considered to be fully reversible in the course of a prolonged observation period of 21 days because a clear tendency of remission was already detectable within the shortened observation period. Therefore, the test item has to be classified for eye irritation, category 2 according to Regulation (EC) No 1272/2008.