Disodium 2,2'-(9,10-dioxoanthracene-1,4-diyldiimino)bis(5-methylsulphonate)

Endpoint summary

Description of key information

Non-irritating to rabbit skin. 

Not irritating to rabbit eyes. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

May 26, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The original study report has a Klimisch Score = 2.

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO).

Deviations:

not specified

Principles of method if other than guideline:

Test method similar to OECD 404.

GLP compliance:

no

Remarks:

pre GLP

Species:

rabbit

Strain:

other: Russian breed

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.6 to 2.0 kg
- Housing: individually in metal cages
- Diet: standard rabbit food - NAFAG Gossau SG- ad libitum
- Water: ad libitum
- Acclimation period: for a minimum of 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 1
- Humidity (%): 55 ± 5 %
- Photoperiod (hrs dark / hrs light): 14 hours light cycle day

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

6 (3 males and 3 females)

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: gauze patches

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Interpretation of results:

other: CLP criteria not met

Conclusions:

The skin irritation was determined in an irritation test on rabbits according to Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO), similar to OECD guideline 404. It was concluded that the test substance is not irritating to rabbit skin.

Executive summary:

Method:

The skin irritation was determined in an irritation test on rabbits according to Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO), similar to OECD guideline 404.

Result:

Not irritant.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

June 04, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Principles of method if other than guideline:

patch test

GLP compliance:

no

Species:

rabbit

Strain:

other: Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.4-1.7 kg
- Housing: singly in metal cages (overall dimensions 47x32x34 cm)
- Diet: standard diet of Nafag ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18±1
- Humidity (%): 55±5
- Photoperiod (hrs dark / hrs light): 14 hours light

Type of coverage:

occlusive

Preparation of test site:

other: right shaved; left shaved+scarified

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g

VEHICLE
- Amount(s) applied (volume or weight with unit): wetted with tap water

Duration of treatment / exposure:

24 h

Observation period:

8 days

Number of animals:

6 (3 male and 3 female)

Details on study design:

TEST SITE
- Area of exposure: 2 sites of 2.5 x 2.5 cm
- Type of wrap if used: impermeable foil of 5 x 5 cm, which was fixed to the body of the animals with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Interpretation of results:

other: CLP criteria not met

Conclusions:

The Skin irritation was determined in an irritation test on rabbits according to the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO)", similar to the OECD Guideline 404. It was concluded that the test substance is not irritating to rabbit skin.

Executive summary:

Method:

The Skin irritation was determined in an irritation test on rabbits according to the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO)", similar to the OECD Guideline 404.

Result:

Not irritant

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:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

June 1 to 4, 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The test was conducted by means of a read-across approach. The reliability of the source study report is 1.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintier farm Madoerin AG EH 4414 Fuellinsdorf/Switzerland
- Age at study initiation: 14 - 15 weeks
- Weight at study initiation: 2.8 kg
- Housing: Indlvidually in stainless steel cages equipped with an automatic cleaning and drinking system.
- Diet: PeIIeted standand KIiba 34L, Batch 25/87 and 26/87 rabbit maintenance diet ("KIiba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland) ad libitum
- Water: ad libitum
- Acclimation period: Five days under laboratory conditions aften veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 40-70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light/12 hours dark

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 g

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Interpretation of results:

other: CLP criteria not met

Conclusions:

The eye irritation was determined in an irritation test on rabbits according to OECD Guideline 405 and EU Method B.5. It was concluded that the test substance is not irritating to the eyes of rabbits.

Executive summary:

Method:

The eye irritation was determined in an irritation test on rabbits according to OECD Guideline 405 and EU Method B.5.

Observation:

The mortality was evaluated daily while the body weights was assessed at day 1 and at termination of the test on a Mettler PK 16 balance. The eyes of each animal were examined 1, 24, 48 and 72 hours after administration. The corrosive properties of the test article and the colour of the treated eye were described and recorded. 

Result:

Non irritant

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No experimental studies are available for the substance in itself.

Nevertheless studies were conducted on analogue substances. Further information are reported in the Read Across justification attached to section 13.

 

Skin Irritation

Similar Substance 01 was evaluated for its skin irritation potential according to the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO)", similar to the OECD Guideline 404. No information are available about the composition of the batch tested.

0.5 g of the test substance was applied on the skin of six rabbits using gauze patches, then covered by impermeable material. After 24 hours the gauzes were removed and the skin observed for 8 days.

The mean score of observed values of irritation/corrosion, calculated for each rabbit, after 24, 48, 72 hours, were always under the limit for irritation potential set out in the OECD guideline, therefore the substance is considered as non irritant.

To support this result a second study conducted on the Similar Substance 02 was taken in account.

The skin irritation was determined in an irritation test on rabbits according to Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (1959), the US Association of Food and Drug Officials (AFDO), similar to OECD guideline 404. The test substance resulted to be not irritant.

 

Eye Irritation

Analogue substance 01 was evaluated for its eye irritation potential according to the OECD Guideline 405 and EU Method B.5.

The test article (0.1 g per animal) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The right eye remained untreated and served as the reference control. The eyes of the animals were observed for 72 hours.

The mean score of observed values of irritation/corrosion, calculated for each rabbit, after 24, 48, 72 hours, were always under the limit for irritation potential set out in the OECD guideline, therefore the test item does not show any eye irritation potential.

Justification for classification or non-classification

SKIN IRRITATION/CORROSION

A corrosive substance is a substance that produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least 1 tested animal after exposure up to 4 hour duration.

Three sub-categories are provided within the Corrosive category 1:

- Subcategory 1A where responses are noted following up to 3 minutes exposure and up to 1 hour observation;

- Subcategory 1B where responses are described following exposure between 3 minutes and 1 hour and observations up to 14 days;

- Subcategory 1C where responses occur after exposures between 1 hour and 4 hours and observations up to 14 days;

To classify a substance as irritant, the major criterion is that at least 2 of 3 tested animals have a mean score of ≥ 2.3 - ≤ 4.0.

Category 2:

- Mean value of ≥ 2.3 - ≤ 4.0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

- Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

- In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical eposure in a single animal but less than the criteria above.

The substance is not classified as skin irritant because in the performed test it doesn't meet the classification criteria of the CLP regulation n. 1272/2008.

 

EYE IRRITATION

Serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance to the anterior surface of the eye, which is not fully reversible within 21 days of application.

Eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

Irreversible effects on the eye (Category 1):

If, when applied to the eye of an animal, a substance produces:

- At least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/ or

- At least in 2 of 3 tested animals, a positive response of corneal opacity ≥ 3 and/or iritis > 1.5 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

These observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, discoloration of the cornea by a dye substance, adhesion, pannus, and interference with the function of the iris or other effects that impair sight. In this context, persistent lesions are considered those which are not fully reversible within an observation period of normally 21 days. Substances are also classified in Category 1 if they fulfil the criteria of corneal opacity ≥ 3 or iritis > 1.5 detected in a Draize eye test with rabbits, recognising that such severe lesions usually do not reverse within a 21-day observation period.

Irritating to eyes (Category 2)

when applied to the eye of an animal, a substance produces:

- At least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 1 and/or iritis ≥ 1, and/or conjunctival redness ≥ 2 and/or conjunctival oedema (chemosis) ≥ 2;

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

The substance is not classified as eye irritant because in the performed test it doesn't meet the classification criteria of the CLP regulation n. 1272/2008.