5,5'-(1H-isoindole-1,3(2H)-diylidene)dibarbituric acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

5,5'-(1H-isoindole-1,3(2H)-diylidene)dibarbituric acid

EC Number:

253-256-2

EC Name:

5,5'-(1H-isoindole-1,3(2H)-diylidene)dibarbituric acid

Cas Number:

36888-99-0

Molecular formula:

C16H9N5O6

IUPAC Name:

5,5'-(1H-isoindole-1,3(2H)-diylidene)dipyrimidine-2,4,6(1H,3H,5H)-trione

Test material form:

solid: nanoform

Details on test material:

- Physical state: Solid; ground / dark yellow
- Analytical purity: 92 %
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Storage condition of test material: Room temperature

Specific details on test material used for the study:

- Physical state: Solid; ground / dark yellow
- Analytical purity: 92 %
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Storage condition of test material: Room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: about 6 months
- Weight at study initiation: 3.60 kg - 3.95 kg
- Housing: single
- Diet (e.g. ad libitum): Kliba-Labordiaet (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g per animal per day)
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12h/12h

Check for dead or moribund animals: Twice each workday (beginning and end) and once on Saturdays, Sundays and on public holidays.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated left eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL bulk volume (about 26 mg of the comminuted test substance)
- Concentration (if solution): undiluted

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1, 24, 48, 72 h and 7 days after application

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
The treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure:
About 1 hour after application of the solid test substance

SCORING SYSTEM: Draize test

TOOL USED TO ASSESS SCORE:
Daylight tubes "Lumilux" (L 58W/860 PLUS EGO 25X1, Osram, Germany)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

1.22

Max. score:

3

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: see table for details

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 24/48 h

Remarks on result:

other: fully reversible in 1/3 animals within 24 h, in 2/3 animals within 48 h

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

2

Results 9

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

2

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48 and 72h (mean)

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48 and 72h (mean)

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 13

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48 and 72h (mean)

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 14

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48 and 72h (mean)

Score:

0

Max. score:

3

Results 15

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48 and 72h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 16

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48 and 72h (mean)

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72h

Other effects:

Discharge: mean 24 - 72 h: 0.22/max.score 3; reversible in 1/3 animals within 24 h; in 2/3 animals within 48 h.

Any other information on results incl. tables

Animal	Reading	Cornea		Iris	Conjunctiva			Additional findings
		Opacity	Cornea area		Redness	Chemosis	Discharge
1	1 h	0	0	0	2	1	1	Scleral vessels injected, circular
2	1 h	0	0	0	2	1	2	Scleral vessels injected, circular
3	1 h	0	0	0	2	1	2	Scleral vessels injected, circumscribed area
1	24 h	0	0	0	2	0	0	Scleral vessels injected, circumscribed area
2	24 h	0	0	0	2	1	1	Scleral vessels injected, circumscribed area
3	24 h	0	0	0	2	1	1	Scleral vessels injected, circumscribed area
1	48 h	0	0	0	1	0	0	Scleral vessels injected, circumscribed area
2	48 h	0	0	0	1	0	0	Scleral vessels injected, circumscribed area
3	48 h	0	0	0	2	0	0	Scleral vessels injected, circumscribed area
1	72 h	0	0	0	1	0	0	Scleral vessels injected, circumscribed area
2	72 h	0	0	0	0	0	0	Study discontinued because the animal was free of findings
3	72 h	0	0	0	0	0	0	Study discontinued because the animal was free of findings
1	7 d	0	0	0	0	0	0
mean	animal 1 24 - 72 h	0.00		0.00	1.33	0.00
mean	animal 2  24 - 72 h	0.00		0.00	1.00	0.33
mean	animal 3  24 - 72 h	0.00		0.00	1.33	0.33
mean	total 24 - 72 h	0.00		0.00	1.22	0.22

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met