N-(4-amino-9,10-dihydro-3-methoxy-9,10-dioxo-1-anthryl)benzenesulphonamide

Endpoint summary

Description of key information

Under the experimental conditions FAT 36034 did not induce skin irritation as well as eye irritation in animals.

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:

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:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 9300102
- Expiration date of the lot/batch: July, 1998

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Weight at study initiation: weighing between 2280 to 2380 g
- Housing: The animals were housed individually in metal cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20 ± 3
- Humidity (%):30-70
- Photoperiod (hrs dark / hrs light):12 hours light cycle day

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: distilled water

Controls:

not specified

Amount / concentration applied:

0.5 g of the test article

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, and 72 hours

Number of animals:

3 female rabbits

Details on study design:

Method
An area of at least 36 cm2 was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm2) bearing 0.5 g of the test article was applied to the right flank of each animal. The skin area exposed directly to the test article was approx. 6 cm2. A control gauze patch was applied to the contralateral flank. Before application both patches were moistened with distilled water.
The patches were loosely covered with an aluminum foil (approx. 36 cm2 ) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg). The animals were checked daily for systemic symptoms and mortality (only findings reported).
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system (Appendix 1). In order to determine the reversibility of the skin reactions additional evaluations of the treated skin were needed in this study.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.56

Max. score:

4

Reversibility:

fully reversible

Because reactions were observed within 72 hours after removing the bandages, the observation period was extended to 7 days to determine the reversibility of the skin reactions. According to the EEC classification of the results obtained 2 4 to 72 hours after removing the bandages FAT 36034/D can be classified as non-irritant in albino rabbits. The skin reactions observed were reversible until the end of the observation period on day 7.

Interpretation of results:

not irritating

Conclusions:

FAT 36034/D can be classified as non-irritant in albino rabbits.

Executive summary:

An acute skin irritation/corrosion study was performed in rabbits to determine the irritant or corrosive potency of FAT 36034/D on the albino rabbit skin. This test was based on the OECD guideline No. 404. Under the experimental conditions employed FAT 36034/D induced erythema reactions when applied to the clipped albino rabbit skin. Because the mean values (0.56 for erythema and 0 for edema) of the recordings up to72 hours after application are below the threshold of significance (2 score for erythema or edema) FAT 36034/D can be classified as non-irritant according to Council Directive 67/548/EEC, adapted to technical progress by Commission Directive 93/21/EEC. According to the EEC classification of the results obtained after removing the bandages FAT 36034/D can be classified as non-irritant to albino rabbits.

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:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 9300102
- Expiration date of the lot/batch: July, 1998

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Weight at study initiation: between 2220 to 2490 g
- Housing: The animals were housed individually in metal cages.
- Diet (e.g. ad libitum):The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water (e.g. ad libitum):Fresh water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20 ± 3
- Humidity (%):30-70
- Photoperiod (hrs dark / hrs light):12 hours light cycle day.

Vehicle:

water

Controls:

other: The right eye remained untreated and served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (46 mg)

Duration of treatment / exposure:

The test substance was not flushed out of the eye.

Observation period (in vivo):

1, 24, 48, and 72 hours

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

Method
0.1 ml (46 mg) of FAT 36034/D was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article.
The right eye remained untreated and served as a control. The animals were checked daily for systemic symptoms and mortality (only findings reported).
 
The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of FAT 36034/D according to the OECD scoring system (Appendix 1). In order to determine the reversibility of the eye reactions additional evaluations of the ocular reactions were needed in this study. A slit-lamp was used to facilitate the evaluation. The irritant/corrosive potency of FAT 36034/D was classified according to Council Directive 67/548/EEC, adapted to technical progress by Commission Directive 93/21/EEC

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Because reactions were observed within 72 hours after instillation of the test article , the observation period was extended to 7 days to determine the reversibility of the eye reactions.

Individual eye scores

Animal No 002/F

Time point	Cornea (ce/te)	Iris (ce/te)	Conjunctiva
			Redness (ce/te)	Chemosis (ce/te)
After 24 hours	0/0	0/0	0/0	0/0
After 48 hours	0/0	0/0	0/1	0/0
After 72 hours	0/0	0/0	0/1	0/0
Mean (24-72 Hrs)	0/0	0/0	0/0.67	0/0

 

Animal No 092/F

Time point	Cornea (ce/te)	Iris (ce/te)	Conjunctiva
			Redness (ce/te)	Chemosis (ce/te)
After 24 hours	0/0	0/0	0/1	0/0
After 48 hours	0/0	0/0	0/1	0/0
After 72 hours	0/0	0/0	0/1	0/0
Mean (24-72 Hrs)	0/0	0/0	0/1	0/0

 

Animal No 040/F

Time point	Cornea (ce/te)	Iris (ce/te)	Conjunctiva
			Redness (ce/te)	Chemosis (ce/te)
After 24 hours	0/0	0/1	0/1	0/0
After 48 hours	0/0	0/0	0/1	0/0
After 72 hours	0/0	0/0	0/1	0/0
Mean (24-72 Hrs)	0/0	0/0.33	0/1	0/0

ce = control eye

te = test eye

Reversibility of any observed effect: Changes fully reversible within 7 days.

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 36034/D can be classified as non-irritant.

Executive summary:

An acute eye irritation/corrosion key study was performed in NZW rabbits to determine the irritant or corrosive potency of FAT 36034/D on the NZW rabbit eye and the associated mucous membranes. This test was based on the OECD guideline No. 405, adopted May 12, 1981, by the OECD council and as well as followed the GLP guidelines. The substance was tested at the concentration of 94% purity. Under the experimental conditions applied FAT 36034/D induced reactions of the cornea, iris and conjunctiva when instilled into the conjunctival sac of albino rabbit eyes. Because the mean values (0.89 for conjunctiva/redness; and 0.11 for iris) of the readings 24 to 72 hours after instillation are below the threshold of significance, FAT 36034/D can be classified as non-irritant according to Council Directive 67/548/EEC, adapted to technical progress by Commission Directive 93/21/EEC.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

A study was performed to determine the skin irritation potential of FAT 36034 D female NZW rabbits. This test was based on the OECD guideline No. 404. Under the experimental conditions, FAT 36034D induced erythema reactions when applied to the NZW rabbit skin. Because the mean score values (0.56 for erythema and 0 for edema) up to 72 hours after application are below the threshold of significance (2 score for erythema or edema) FAT 36034D was classified as non-irritant according to Council Directive67/548/EEC.

An in vivo study was performed according to OECD test guideline 405 to determine the eye irritation potential of FAT 36034/D having a purity of 94% on rabbit eyes. Under the experimental conditions FAT 36034/D when instilled into the conjunctival sac of female NZW rabbit eyes induced reactions on the cornea, iris and conjunctiva. The mean score values at 24 to 72 hours after instillation are below the threshold of significance. Hence, FAT 36034/D can be classified as non-irritant according to Council Directive 67/548/EEC. An in vitro test performed in compliance with GLP and OECD guideline 437 " Bovine Corneal Opacity and Permeability Assay", the test item FAT 36034/H when exposed to Bovine cornea showed an in vitro Irritancy Score of 2.2. An in vitro Irritancy Score of≤3 warrants for Not classified for irritation according to UN GHS and European Regulation (EC) 1272/2008. Additionally, in the in vivo key studies conducted on NZW rabbits with FAT 36034 (FAT 36034 D (3 female) &FAT 36034/E (3 male)) as per OECD 405 guideline, the mean score at 24 to 72 hours after application were below the level of significance, FAT 36034/C can be classified as non-irritant according to the EEC directive No.83/467/1983. In a supporting study, FAT 36034/C with 40.8% purity induced irritation of the conjunctiva when applied into the conjunctival sac of NZW rabbits. Since the mean score at 24 to 72 hours after application were below the level of significance, FAT 36034/C can be classified as non-irritant according to the EEC directive No.83/467/1983.

Considering the key study results and compound tested up to high purity level at 94 %, and reversible changes of reactions observed the substance FAT36034 can be classified as non-irritant to eyes in both in vitro and in in vivo.

Justification for classification or non-classification

Disperse Red 86:1 was considered to be not irritating based on the available information, hence it does not warrant classification for irritation as per the criteria of Regulation (EC) No. 1272/2008.