Trichloro-12,24-dihydro-5H-naphtho[2,3-h]naphth[2'',3'':6',7']indolo[2',3':6,7]anthra[2,1,9-mna]acridine-5,10,13,18,25-pentone

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

12 October 1993 to 15 October 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction product of 3,9-dibromobenzanthrone condensed with 2 equivalents of 1-aminoanthraquinone, subsequently further condensed under oxidative conditions

EC Number:

944-232-9

Molecular formula:

Not available - UVCB substance

IUPAC Name:

Reaction product of 3,9-dibromobenzanthrone condensed with 2 equivalents of 1-aminoanthraquinone, subsequently further condensed under oxidative conditions

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test species: New Zealand albino rabbit
Strain: Chbb: NZW (SPF)
Origin: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 88400 Biberach
Number of animals: 3
Animal identification: numbered ear tags
Animal weights: 2.6 - 2.9 kgAge of animals: about 3 - 5 months
Animal housing: in fully air-conditioned rooms, separate cages (arranged in a battery)
Ambient temperature: 18 ± 3 °CRelative humidity: 55 ± 20 %
Lighting time: 12 hours per day
Diet: Altromin 2123 maintenance diet – rabbits (Altromin GmbH, Lage/Lippe), ad libitum and hay (approx. 15 g daily)
Drinking water: deionised, chlorinated water from automatic water dispensers, ad libitum

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

physiological saline

Controls:

not specified

Amount / concentration applied:

Each animal was treated with 0.5 g lndanthren-Oliv HT Colloisol pasted with 0.3 ml isotonic saline.

Duration of treatment / exposure:

The exposure period was 4 hours.

Observation period:

Examinations of the skin took place after 30 - 60 minutes, and 24, 48 and 72 hours after removal of the patches.

Number of animals:

3 rabbits

Details on study design:

About 24 hours before the start of the study the hair in the dorsal region of the body of 3 rabbits was removed with an electric clipper over an area of about 25 cm2. Only animals with intact skin were used. Each animal was treated with 0.5 g lndanthren-Oliv HT Colloisol pasted with 0.3 ml isotonic saline. The substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster (specially produced by Beiersdorf AG, Hamburg). The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage. The exposure period was 4 hours. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water. Examinations of the skin took place after 30 - 60 minutes, and 24, 48 and 72 hours after removal of the patches.Erythema, eschar formation and oedema were evaluated numerically according to the technique of DRAIZE (see Any other information, Scale for scoring dermal reactions).All other changes of the skin were recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

From 30 minutes up to 24 hours after removal of the patches the treated skin of all animals showed very slight up to moderately strong erythema as well as up to 48 hours p.a. a barely perceptible erythema in one animal.72 hours after removal of the patches the irritations were reversible.

Other effects:

None specified

Any other information on results incl. tables

 

ANIMAL NUMBER	ERYTHEMA				MEAN SCORE	OEDEMA				MEAN SCORE
	Time after decontamination					Time after decontamination
	30-60 MIN	1 DAY	2 DAYS	3 DAYS		30-60 MIN	1 DAY	2 DAYS	3 DAYS
60	3	2	0	0	0.7	0	0	0	0	0.0
61	2	1	0	0	0.3	0	0	0	0	0.0
62	2	2	1	0	1.0	0	0	0	0	0.0
	OVERALL MEAN: 0.7					OVERALL MEAN: 0.0

 The mean has been calculated using the day 1, 2 & 3 values

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study lndanthren-Oliv HT Colloisol is slightly irritating to skin. Based on the results of this study, the test substance is not classified as a skin irritant in accordance with the CLP Regulation.

Executive summary:

Testing for primary dermal irritation provides information on the irritant effect of the test substance on the skin following a single dermal application and serves as a basis for classification and labelling.

The present study was conducted in compliance with:

-EEC Directive B.4. 'Acute toxicity Skin Irritation' of the Directive 84/449/EEC: Commission Directive of 25 April 1984 adapting to technical progress for the sixth time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances

-OECD Guidelines for Testing of Chemicals, 404 "Acute Dermal Irritation/Corrosion", OECD 1981

Updated guideline, adopted: 17th July 1992

-The study was conducted in compliance with the Principles of Good Laboratory Practice Annex of paragraph 19a, section 1 of the chemical law from August 1990

 

About 24 hours before the start of the study the hair in the dorsal region of the body of 3 rabbits was removed with an electric clipper over an area of about 25 cm². Only animals with intact skin were used.

Each animal was treated with 0.5 g lndanthren-Oliv HT Colloisol pasted with 0.3 ml isotonic saline. The substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster (specially produced by Beiersdorf AG, Hamburg). The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.

The exposure period was 4 hours. After the exposure period all remnants of the test substance were carefully removed from the skin with warm tap water.

Examinations of the skin took place after 30 - 60 minutes, and 24, 48 and 72 hours after removal of the patches.

 

From 30 minutes up to 24 hours after removal of the patches the treated skin ofall animals showed very slight up to moderately strong erythema as well as up to 48 hours p.a. a barely perceptible erythema in one animal.

72 hours after removal of the patches the irritations were reversible.

 

Based on the results of this study lndanthren-Oliv HT Colloisol is slightly irritating to skin.