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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

October 19th, 1993 to October 29th, 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:

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

Test guideline 2

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

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 / tissue source

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

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

Remarks on result:

probability of weak irritation

Results 4

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

Remarks on result:

probability of weak irritation

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.