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

Endpoint summary

Description of key information

Skin Irritation in vivo

Based on the results of the key study in vivo study, the test substance is not classified as a skin irritant.

Eye Irritation in vivo

Based on the results of in vivo studies, the test substance is not classified as an eye irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 October 1993 to 15 October 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes

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

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.

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

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

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

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

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

 

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 19th, 1993 to October 29th, 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

EEC Directive 8.5. 'Acute toxicity Eye 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

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

OECD Guidelines for Testing of Chemicals, 405 "Acute Eye Irritation/Corrosion", OECD 1981 Updated Guideline, adopted: 24th February 1987

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues 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: 3Animal identification: numbered ear tags
Animal weights: 2.8 - 3.7 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: 50 ± 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

Vehicle:

not specified

Controls:

other: Untreated eyes acted as controls

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

Single exposure, 24 hour treatment period

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 animals

Details on study design:

About 24 hours before the start of the study the test eyes of all animals were examined under UV light for corneal lesions after instillation of one drop of a 0.01 % fluorescein-sodium solution. Only animals without ocular abnormalities were used for the study.100 mg lndanthren-Oliv HT Colloisol was applied once to the conjunctival sac of the left eye of 3 rabbits. The untreated eyes served in each case as a control.24 hours after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein-sodium solution took place, the treated eyes were washed out thoroughly with physiological saline at approx. 37 °C.The eyes were examined 1, 24, 48 and 72 hours after application of the test substance. At 24 and 72 hours the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01 %fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis 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:

One hour p.a. the conjunctiva of the animals showed slight to obvious swelling with partial eversion of lids as well as up to 24 hours p.a. evident hyperaemie to diffuse deeper crimson coloured reddenings.48 hours p.a. the irritations were reversible.

Other effects:

Additional a clear from the substance discoloured discharge was observed.

RABBIT EYE IRRITATION TEST - READINGS

Animal Number	Sex	Eye Used	Initial Pain Reaction	Irrigation	Elapsed Time	CORNEA		IRIS	CONJUNCTIVAE
						OPACITY	AREA		REDNESS	CHEMOSIS	DISCHARGE
55	F	LEFT	NONE	24 HRS	1.0   HRS 1 DAY 2 DAYS 3 DAYS	0 0 0 0	0 0 0 0	0 0 0 0	2 1 0 0	2 0 0 0	1 0 0 0
90	F	LEFT	NONE	24 HRS	1.0 HRS 1 DAY 2 DAYS 3 DAYS	0 0 0 0	0 0 0 0	0 0 0 0	1 1 0 0	1 0 0 0	2 0 0 0
92	F	LEFT	NONE	24 HRS	1.0 HRS 1 DAY 2 DAYS 3 DAYS	0 0 0 0	0 0 0 0	0 0 0 0	2 0 0 0	1 0 0 0	2 0 0 0

 

 

ADDITIONAL INFORMATION

S = slight	X = finding present
M = moderate	N = previous finding reversible
E = extreme	? = not assessable

 

Animal Number	Clinical Observation Dosed Eye	Time After Dosing
		1 HR	1 DAY	2 DAYS	3 DAYS
55	Eye Disch. Clear, Subst. Col No Abnormalities Detected Killed at End of Study	X	N	N	X
Animal Number	Clinical Observation Control Eye	Time After Dosing
		1 HR	1 DAY	2 DAYS	3 DAYS
55	No Abnormalities Detected	N	N	N	N

INITIAL BODYWEIGHT: 2790.0 g

FLUORESCEIN STAINING: Time after dosing:       1 Day 0

                                                              3 Days 0

EYE TEXT: No Text Recorded

COMMENTS: No Commented Recorded

 

Animal Number	Clinical Observation Dosed Eye	Time After Dosing
		1 HR	1 DAY	2 DAYS	3 DAYS
90	Eye Disch. Clear, Subst. Col No Abnormalities Detected Killed at End of Study	X	N	N	X
Animal Number	Clinical Observation Control Eye	Time After Dosing
		1 HR	1 DAY	2 DAYS	3 DAYS
90	No Abnormalities Detected	N	N	N	N

INITIAL BODYWEIGHT: 3740.0 g

FLUORESCEIN STAINING: Time after dosing:       1 Day 0

                                                              3 Days 0

EYE TEXT: No Text Recorded

COMMENTS: No Commented Recorded

 

Animal Number	Clinical Observation Dosed Eye	Time After Dosing
		1 HR	1 DAY	2 DAYS	3 DAYS
92	Eye Disch. Clear, Subst. Col No Abnormalities Detected Killed at End of Study	X	N	N	X
Animal Number	Clinical Observation Control Eye	Time After Dosing
		1 HR	1 DAY	2 DAYS	3 DAYS
92	No Abnormalities Detected	N	N	N	N

INITIAL BODYWEIGHT: 3360.0 g

FLUORESCEIN STAINING: Time after dosing:       1 Day 0

                                                              3 Days 0

EYE TEXT: No Text Recorded

COMMENTS: No Commented Recorded

 

RABBIT EYE IRRITATION TEST - ANALYSIS

	MEAN SCORE (1 DAY – 3 DAYS AFTER DOSING)
ANIMAL NUMBER	CORNEA	IRIS	CONJUNCTIVA
	OPACITY		REDNESS	CHEMOSIS
55	0.00	0.00	0.33	0.00
90	0.00	0.00	0.33	0.00
92	0.00	0.00	0.00	0.00
GROUP MEAN SCORE	0.00	0.00	0.22	0.00

Interpretation of results:

GHS criteria not met

Conclusions:

Testing of Indanthren-Oliv HT Colloisol for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.

Executive summary:

Testing for primary irritation in the rabbit eye provides information on ocular lesions after a single application of the test substance to the conjunctival sac of the eye and serves as a basis for classification and labelling.

 

The study was conducted in compliance with:

EEC Directive 8.5. 'Acute toxicity Eye 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, 405 "Acute Eye Irritation/Corrosion", OECD 1981 Updated Guideline, adopted: 24th February 1987

 

Testing of Indanthren-Oliv HT Colloisol for primary eye irritation in the rabbit showed, that the substance is not irritating to eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the key in vivo skin irritation study, 0.5 g of the test material (containing 46.2% of the test substance) was applied to the intact, shaved skin of each of 3 New Zealand, albino rats. The substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plaster; the plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage. 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. The erythema was reversible in all animals within 72 hours. It was concluded that the test substance is slightly irritating to the skin, however, the results of this study do not trigger classification of the test substance as a skin irritant in accordance with the CLP Regulation.

There are also four supporting in vivo skin irritation studies available:

In the first study, 0.5 ml of the test material (containing ca. 40% of the substance) was applied to intact and abraded, shaved skin of each of 6 New Zealand, albino rats. Extremely superficial second degree chemical burns were noted at the 24-hour scoring interval on all sites (the erythema was not reversible after 72 hours at all sites). The burns were considered too superficial to be given a maximum score of four for both erythema and oedema. For all the intact skin sites, the mean erythema score was 2.8 after 72 hours.

In the second study, the test material (containing 43.5% of the substance) was applied to the intact and abraded, shaved skin of each of 6 rabbits of the Russian breed. The primary irritation index was 0.1 indicating that the substance is a mild irritant to the rabbit skin.

In the third study, the test material (containing 43.5% of the substance) was applied to the intact and abraded, shaved skin of each of 6 rabbits of the Russian breed. Under the conditions of the experiment the test preparation was found to cause no irritation when applied to intact skin and to abraded rabbit skin.

In the fourth study, the test material (containing 43.5% of the substance) was applied to the intact and abraded, shaved skin of each of 6 rabbits of the Russian breed. Under the conditions of the experiment the test preparation was found to cause no irritation when applied to intact skin and slight irritation when applied to abraded rabbit skin.

In the key in vivo eye irritation study, 100 mg of the test substance (containing 46.2% of the test substance) was applied to the left eye of each of 3 New Zealand Albino rabbits. The treated eyes were washed 24 hours after application. Redness of the conjunctiva was observed 1 hour after the application, reversible after 48 hours (mean score of 0.2). Therefore, these results do not trigger classification of the test substance as an eye irritant in accordance with the CLP Regulation.

There are also four supporting in vivo eye irritation studies available:

In the first study, 0.1 ml of the test material (containing ca. 40% of the substance) was applied to the right eye of each of 6 young, albino rabbits of the New Zealand strain. The test material was practically non-irritating.

In the second study, 0.1 ml of the test material (containing 43.5% of the substance) was applied to the right eye of each of 6 rabbits of the Russian breed. In 3 rabbits, approximately 30 seconds after administration, the treated eyes were flushed with water. The primary irritation index, a measure of the acute eye irritation provoked by the substance, was 0 for the cornea, 0 for the iris and 0 for the conjunctivae. This indicates that the substance is not an irritant to the rabbit eye.

In the third study, 0.1 ml of the test material (containing 43.5% of the substance) was applied to the right eye of each of 6 rabbits of the Russian breed. In 3 rabbits, approximately 30 seconds after administration, the treated eyes were flushed with water. Under the conditions of the experiment that test preparation was found to cause practically no irritation when applied to the rabbit eye mucosa.

In the fourth study, 0.1 ml of the test material (containing 43.5% of the substance) was applied to the right eye of each of 6 rabbits of the Russian breed. In 3 rabbits, approximately 30 seconds after administration, the treated eyes were flushed with water. Under the conditions of the experiment that test preparation was found to cause practically no irritation when applied to the rabbit eye mucosa.

Justification for classification or non-classification

The test substance is not classified as either a skin irritant or as an eye irritant in accordance with the CLP Regulation.