2,9-dimethylanthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetrone

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 5th, 1983 - July 8th, 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Remarks:

but QAU statement included

Test material

Test material information

Constituent 1

Reference substance name:

2,9-dimethylanthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetrone

EC Number:

226-866-1

EC Name:

2,9-dimethylanthra[2,1,9-def:6,5,10-d'e'f']diisoquinoline-1,3,8,10(2H,9H)-tetrone

Cas Number:

5521-31-3

Molecular formula:

C26H14N2O4

IUPAC Name:

2,9-dimethylisoquino[4',5',6':6,5,10]anthra[2,1,9-def]isoquinoline-1,3,8,10(2H,9H)-tetrone

Details on test material:

Test materials used in this dossier are all considered to fall under the definition of nano-materials according to the European Commission Recommendation 2011/696/EU as the synthesis and manufacturing of this pigment always yields particulate material with a fine particle size distribution.

Specific details on test material used for the study:

- Physical state: solid (powder)
- technical grade
- Storage condition of test material: in the dark at room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG breed
- Weight at study initiation: 3.5 - 3.9 kg
- Housing: individually
- Diet (e.g. ad libitum): Altromin 2013 breedingdiat - rabbit (Altromin GmbH, Lage/Lippe), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): fully conditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

other: polyethylenglycol 400

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg in 0.01 mL polyethylenglycol 400

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with physiological NaCl solution of 37 °C (0.01%)
- Time after start of exposure: 24 hours

SCORING SYSTEM: According to OECD test guideline

TOOL USED TO ASSESS SCORE: magnifier, fluorescein solution (0.01%) and UV light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: fluorescent test

Basis:

mean

Time point:

24/48/72 h

Score:

0

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: after 1 h of exposure the iris was brownish colored in two of the animals

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of irritation were observed for the iris and the cornea at 24-72h timepoints. After 1 h of exposure the iris was brownish colored in two of the animals. A moderate (grade 1) redness and swelling of the conjunctival sac was observed after 1 h of exposure which both decreased gradually. No swelling was observed from 24 hours onwards and no redness was observed at 72 hours.

Any other information on results incl. tables

overview of results:

		Animal 1	Animal 2	Animal 3
cornea	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
redness	1 h	1	1	1
	24 h	1	1	0
	48 h	1	0	0
	72 h	0	0	0
chemosis	1 h	1	0	1
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
Iris	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was investigated for its potential to be irritant to eyes. All effects observed were fully reversible within 72 h and thus, it was concluded that the test substance is not irritating to eyes.

Executive summary:

In the key study according to OECD guideline 405, the test article (0.1 g in 0.01 ml polyethylenglycol 400) was applied into the left conjunctival sac of three New Zealand White rabbits. The untreated right eyes served as controls. The treated eyes were washed with physiological NaCl solution 24 hours after instillation. Animals were observed 1, 24, 48 and 72 hours after test item instillation. After 1 h of exposure the iris was brownish colored in two of the animals. A moderate (grade 1) redness and swelling of the conjunctival sac was observed after 1 h of exposure which both decreased gradually. No swelling was observed from 24 hours onwards and no redness was observed at 72 hours. The mean (24, 48, 72 hours) cornea, iris and chemosis scores were 0. The mean (24, 48, 72 hours) conjunctivae score was 0.3 (fully reversible within 72 hours). Based on the result of this study, the test article was considered to be not irritating to the eye.