2,9-bis(p-methoxybenzyl)anthra[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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

280-472-4

EC Name:

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

Cas Number:

83524-75-8

Molecular formula:

C40H26N2O6

IUPAC Name:

7,18-bis[(4-methoxyphenyl)methyl]-7,18-diazaheptacyclo[14.6.2.2²,⁵.0³,¹².0⁴,⁹.0¹³,²³.0²⁰,²⁴]hexacosa-1(23),2,4,9,11,13,15,20(24),21,25-decaene-6,8,17,19-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.

Test animals / tissue source

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler; D-6050 Offenbach/Main, FRG
- Weight at study initiation: 2.79, 2,89 and 2.93 kg (individual weights)
- Housing: Stainless steel with wire mesh walk floor, floor area: 40 cm x 51 cm
- Diet (e.g. ad libitum): Ovator Solikanin 4 mm; Muskator-Werke D-4000 Düsseldorf 1, FRG (about 130 g per animal daily)
- Water (e.g. ad libitum): About 250 ml tap water per animal, daily
- Acclimation period: At least approx. 8 days in the skin laboratory before the beginning of the study; same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -24
- Humidity (%): 30 - 70
- Air changes (per hr): Fully airconditioned room
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (ca. 28 mg)

Duration of treatment / exposure:

one single application, no washing was performed

Observation period (in vivo):

1 h, 24 h, 48 h, 72 h, 8 d after application

Number of animals or in vitro replicates:

2 females, 1male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1 h

Score:

2

Max. score:

3

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

not fully reversible within: 8 days (one animal had a conjunctivae score of 1 after 8 days)

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1 h

Score:

1

Max. score:

4

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

The ocular reactions observed were below the regulatory threshold. The remaining redness at the end of observation in one animal is expected to resolve eventually.

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
	8 d	0	0	0
redness	1 h	2	2	2
	24 h	2	2	2
	48 h	1	1	1
	72 h	1	1	1
	8 d	1	0	0
chemosis	1 h	1	1	1
	24 h	1	1	1
	48 h	0	0	0
	72 h	0	0	0
	8 d	0	0	0
Iris	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	8 d	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the test article caused mild ocular reactions below the level of significance and is therefore regarded as not irritating to the rabbit eye.

Executive summary:

In an eye irritation study following OECD guideline 405, 0.1 ml of the test substance was applied undiluted into the eyes of three Vienna White rabbits. The test animals were observed for eight days and irritation scores were recorded 1, 24, 48 and 72 hours and 8 days after the instillation. No effects in the cornea and iris were observed at any observation time point. The mean scores (24, 48, 72 hours) for conjunctival redness and chemosis were 1.3 and 0.3, respectively. One animal displayed a conjunctival redness of at the end of the observation period with a score of 1 (full reversibility is expected after longer observation). Chemosis was fully reversible within 48 hours. Based on the results of this study, the test article caused mild ocular reactions below the level of significance and is therefore regarded as not irritating to the rabbit eye.