3,3'-[(9,10-dihydro-9,10-dioxo-1,4-anthrylene)diimino]bis[N-cyclohexyl-2,4,6-trimethylbenzenesulphonamide]

Endpoint summary

Description of key information

No relevant signs of dermal or ocular irritation were observed in rabbits.

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:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to guideline and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG CH 4414 Fuellinsdorf I Switzerland
- Age at study initiation: 14 - 15 weeks
- Weight at study initiation: 2.4 - 3.0 kg
- Housing:
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libintum
- Acclimation period: Four days under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/- 3
- Humidity (%): 40-70
- Air changes (per hr): > 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: PEG 400

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg / site
- Concentration (if solution): moistened with vehicle

Duration of treatment / exposure:

4 h

Observation period:

7 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 100 cm²
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): luke- warm water
- Time after start of exposure: 4 h

SCORING SYSTEM: OECD TG 404 (1984)

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Score:

ca. 0.7

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 h

Score:

0.4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 h

Score:

0

Irritant / corrosive response data:

The test material showed a primary irritation score of 0.7 when applied to intact rabbit skin.
Local signs (mean 1 hour to 7 day) consisted of grade 0.4 erythema and grade 0.0 edema. They were reversible within 7 days.
No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.

Other effects:

In the area of application a blue staining of the treated skin by the test article (blue pigment) was observed.
The body weight gains of all rabbits were similar. No acute toxic symptoms were observed in the animals during the test period, and
no mortality occurred.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

TREATMENT

Approximately 24 hours before treatment, the dorsal fur was shaved with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm x 10 cm).

On test day 1, 0.5 g of the test article (The test article was moistened with polyethylene glycol )

w

as applied to the intact skin of the shaved area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The duration of treatment was 4 hours.

Four hours after the application, the dressing was removed and the skin was flushed with 1ukewarm tap water. The skin reaction was assessed according to the OECD Guideline for Testing of Chemicals 404. The skin reaction was assessed at 1, 24, 48 and 72 hours and at 7 days after the removal of the dressing, gauze patch and test article.

IRRITATION / CORROSION

The test material showed a primary irritation score of 0.7 when applied to intact rabbit skin. Local signs (mean;1 hour to 7 day) consisted of grade 0.4 erythema and grade 0.0 edema.

They were reversible until day 7.

No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.

Other Findings:

No acute toxic symptoms were observed in the animals during the test period, and no mortality occurred.

The body weight gain of all rabbits was similar.

In the area of application a blue staining of the treated skin by pigment or coloring of the test article was observed.

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:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no GLP; deviations from Guideline

Qualifier:

according to guideline

Guideline:

other: USA Hazardous Substance Act from Sept. 16, 1964

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

6 animals; rinsing of some eyes after 30 s;

GLP compliance:

no

Remarks:

pre-dates GLP regulation

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: KFM (CH-4414 FUllinsdorf, Switzerland)
- Age at study initiation: 14 weeks
- Weight at study initiation: 2,5 +/-0,5 kg
- Housing: individually in stainless cages with grid bottom
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-2
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100mg/eye
- both eyes treated

Duration of treatment / exposure:

right eyes: rinsed with lukewarm water after 30 seconds
left eyes: not limited

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): right eyes after 30 seconds: warm water
SCORING SYSTEM: Draize
TOOL USED TO ASSESS SCORE: none

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Score:

2.5

Max. score:

5

Remarks on result:

other: Eyes not rinsed

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Score:

0.44

Max. score:

0.67

Remarks on result:

other: eyes rinsed after 30 seconds

Irritant / corrosive response data:

In the unrinsed eye redness of the conjunctiva was observed in 5 of 6 rabbits 24 hours after instillation and was accompanied by lid swelling in 3 animals; swelling has disappeared at 48 hours but two animals still showed conjunctival redness.
A slight impairement of the iris function was reported in two cases after 24 hours and in one case after 48 hours. Whereas all irritation effects had disappeared after 72 hours one case of grade 1 redness was reported in one animal after 7 days which is considered unlikely related to the test article. Cornea was at no time involved in the ocular effects.

In the rinsed eye ocular effects were limited to grade 1 redness of the conjunctiva in single animals: .one at 24h and 72h, two at 48h but three after 7 days (!).
That rinsing did not totally eliminated conjunctiva redness could have been due to the strong hydrophobic properties of the test article which, therefore, would not have been totally washed out from the conjunctival sack during the rinsing procedure.

Other effects:

none

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to irritation scores and to the classification system used the test article has been classified a non eye irritant, although some slight ocular effects were reported in the majority of the animals after 24 hours and in some of them after 48 hours.
Rinsing the eye abundantly with water immediately after contamination reduces notably the development of these slight irritation reactions.

Executive summary:

An eye irritation study was performed in rabbit with the test material. The test article,

a blue powder, was of technical grade purity.

Methodology:

The study was designed and conducted accordance with the method recommended by the USA Hazardous Substance Act from Sept. 16, 1964 in the SANDOZ Ltd., Agrotoxicology Dept. in Basle, Switzerland.

Six healthy young adult New Zealand White rabbits were used. Their eyes were determined to be free of pre-existing ocular abnormalities. 100 mg of neat material were administered directly into the conjunctival sacs of both eyes of each rabbit. After about 30 seconds the right eyes were then rinsed with 20 ml of lukewarm water. The left eyes were not rinsed.

The eyes were examined and scored for irritation according to the method of Draize at 24, 48, 72 hours and after 7 days. The system of classification of the irritation potential was based on the average primary irritation score at 24, 48 and 72 hour readings and using the ETAD classification system.

Results and conclusion

Some ocular effects (mainly slight redness of the conjunctiva) were reported in the majority of the animals 24 hours after instillation and in some of them also after 48 hours when the test eye had not been rinsed after the contamination. Cornea was not involved in the irritation. Average irritation scores were 5.67 (of max. 110) at 24 h, 1.83 at 48 h and zero at 72 h post instillation.

According to the ETAD classification scheeme test article, therefore, is classified as a non eye irritant.

Notes

a) Rinsing the eye abundantly with water immediately after contamination notably reduces the risk for developing slight conjunctiva redness.

b) In the US-EPA classification system the test article will probably be classified as minimally irritating to the eye

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant signs of dermal or ocular irritation were observed in rabbits.

Justification for selection of skin irritation / corrosion endpoint:
Study according to guideline and GLP

Justification for selection of eye irritation endpoint:
only 1 study available

Justification for classification or non-classification

As no adverse effects were recorded no classification is warranted.