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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500.42

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

266-564-7

EC Name:

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

Cas Number:

67075-37-0

Molecular formula:

C40H26N2O4

IUPAC Name:

7,18-bis(2-phenylethyl)-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.

Specific details on test material used for the study:

- Physical state: solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: W. Ostrop/Meerbusch
- Weight at study initiation: mean weight: 2.1 kg
- Housing: one per cage
- Diet (e.g. ad libitum): "muemmel z" (ssniff/Soest)
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: 4-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): 40 (relative humidity)
- Photoperiod (hrs dark / hrs light): according to the day light rhythm

Test system

Type of coverage:

occlusive

Preparation of test site:

other: shaved intact and damaged skin

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg compound slightly thickened with water

Duration of treatment / exposure:

24 hours

Observation period:

8 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: double layer gauze covered by indifferent impermeable PVC (5x5 cm) foil and elastic bandage (ElastoflexR)

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

SCORING SYSTEM: Draize numerical scores.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

intact and damaged skin

Basis:

mean

Time point:

24 h

Remarks on result:

other: scoring not possible due to the skin coloring by the substance

Results 2

Irritation parameter:

erythema score

Remarks:

intact and damaged skin

Basis:

mean

Time point:

48 h

Remarks on result:

other: timepoint not evaluated

Results 3

Irritation parameter:

erythema score

Remarks:

intact and damaged skin

Basis:

mean

Time point:

72 h

Remarks on result:

other: scoring not possible due to the skin coloring by the substance

Results 4

Irritation parameter:

erythema score

Remarks:

intact and damaged skin

Basis:

mean

Time point:

other: 8 days

Remarks on result:

other: scoring not possible due to the skin coloring by the substance

Results 5

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

24 h

Score:

2.33

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Results 6

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

48 h

Remarks on result:

other: timepoint not evaluated

Results 7

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

72 h

Score:

0.83

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Results 8

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Time point:

other: 8 days

Score:

0.33

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Results 9

Irritation parameter:

edema score

Remarks:

damaged skin

Basis:

mean

Time point:

24 h

Score:

1.83

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Results 10

Irritation parameter:

edema score

Remarks:

damaged skin

Basis:

mean

Time point:

48 h

Remarks on result:

other: time point not evaluated

Results 11

Irritation parameter:

edema score

Remarks:

damaged skin

Basis:

mean

Time point:

72 h

Score:

1.17

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Results 12

Irritation parameter:

edema score

Remarks:

damaged skin

Basis:

mean

Time point:

other: 8 days

Score:

0.33

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritant / corrosive response data:

The test article caused edema formation below the threshold of regulatory significance. In two animals, the edema was not fully reversed after 8 days but is expected to have cleared after 14 days. The erythema reactions could not be scored due to coloring effects of the test substance. Erythema was assumed to be equal to edema based on the correlation existing (Marzulli and Maibach, Foi. Cosm. Tox. 13, 355, 1975).

Any other information on results incl. tables

Overview of results:

		Animal 1	Animal 2	Animal 3	Animal 4	Animal 5	Animal 6
		intact skin
erythema	24 h	*	*	*	*	*	*
	72 h	*	*	*	*	*	*
	8 days	*	*	*	*	*	*
edema	24 h	3	3	1	2	3	2
	72 h	0	1	1	1	1	1
	8 days	0	0	0	1	1	0
		damaged skin
erythema	24 h	*	*	*	*	*	*
	72 h	*	*	*	*	*	*
	8 days	*	*	*	*	*	*
edema	24 h	2	2	0	2	3	2
	72 h	1	0	0	2	2	2
	8 days	1	0	0	0	1	0

* could not be scored due to coloration of the skin from the substance

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The results show that there is no corrosive potential of the substance. However, the substance can not be properly evaluated due to substance residues / coloring. The substance is regarded as slightly irritating, however below the level of regulatory significance.

Executive summary:

The test substance slightly thickened with water (500 mg) was applied to intact and damaged skin of six New Zealand White rabbits in a skin irritation study comparable to OECD guideline 404 but without GLP compliance. The test substance was applied on a tissue (2.5 x 2.5 cm) held in place by an occlusive dressing for 24 hours. The test rabbits were observed for 8 days. Application caused forming of edema (mean scores (24 and 72 hours) for intact and damaged skin were 1.6 and 1.5, respectively). Determination of erythema was not possible at 24 and 72 hours and at day 8 after treatment, due to substance induced coloration of the skin. Therefore, based on the result of this study, the test substance does not have high potential to cause skin irritation, however a definitive conclusion cannot be drawn.