2,9-bis(p-methoxybenzyl)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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

only a 50% aqueous preparation was tested

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 404 (Acute Dermal 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

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler; D-6050 Offenbach/Main, FRG
- 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): 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 rooms
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

other: untreated skin of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 50% aqueous preparation
Application volume: Wetting of the test patch with a layer of approx. 0.5 ml of the 50% preparation (the test patch measures 2.5 x 2.5 cm and thus about 0.5 g is applied; due to the natural moisture of the skin, distilled water is used for preparing the preparations in order to carry out the test under conditions am physiological as possible.

Duration of treatment / exposure:

4 hours

Observation period:

30 - 60 minutes after removal of the test patches and 24 hours, 48 hours, 72 hours and 8 days after the beginning of application

Number of animals:

2 females, 1 male

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with Lutrol and Lutrol/water (1:1)
- Time after start of exposure: 4 h

SCORING SYSTEM: Scale for scoring of erythema and edema:
0 = None
1 = Very slight
2 = Well-defined
3 = Moderate to severe
4 = Severe to very severe

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 4 h

Score:

2

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 3

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 4 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

After 4 hours, erythema score 2 (extending beyond the area of exposure) was observed in all animals; edema score 1 was observed in one animal; edema extending beyond the area of exposure in one animal.
After 24 hours, erythema extending beyond the area of exposure (score 1 in two animals and score 2 in one animal). In two animals, the erythema persisted at score 1 until the 72 h time point. reversibvle within 8 days.

Other effects:

No abnormalities identified at necropsy.

Any other information on results incl. tables

Overview on results:

		Animal 1	Animal 2	Animal 3
erythema	4 h	2	2	2
	24 h	2	1	1
	48 h	1	1	0
	72 h	1	1	0
	8 d	0	0	0
edema	4 h	0	0	1
	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 a mild irritation response below the level of regulatory significance and is therefore considered to be not irritating to the rabbit skin.

Executive summary:

In a skin irritation study following OECD guideline 404, 500 mg of a 50% aequous preparation of the test substance was applied to the left flanks of three Vienna White rabbits. The untreated right flan served as control. The animals were observed for 8 days. An edema extending beyond the area of exposure with a score of 1 was observed in one animal after 4 hours, reversible within 24 hours. In addition, erythema formation (score = 2) was observed in all animals 4 hours after exposure. The erythema extended beyond the area of exposure in all animals at this observation time point. The severity of erythema decreased during the observation period and was fully reversible in all animals within 8 days. The mean (24/48/72 h) erythema and edema scores were 0.9 and 0, respectively. Based on the results of this study, the test article caused a mild irritation response below the level of regulatory significance and is therefore considered to be not irritating to the rabbit skin.