Sodium 1-amino-9,10-dihydro-4-[5-[(2-hydroxyethyl)sulphamoyl]-3,4-xylidino]-9,10-dioxoanthracene-2-sulphonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Proposed Guidelines of the United States Environmental Agency (EPA) $ 163.81-5 "Primary dermal irritation study", Federal Register, Vol. 43, No. 163, August 22, 1978.

Deviations:

yes

Remarks:

(no untreated skin areas to serve as control; exposure period is of 24 h; smaller area of application (i.e., approx. 2.5 cm² gauze pad)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(no untreated skin areas to serve as control; exposure period is of 24 h; smaller area of application (i.e., approx. 2.5 cm² gauze pad)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

FAT 20033/L TE

IUPAC Name:

FAT 20033/L TE

Constituent 2

Reference substance name:

Sodium 1-amino-9,10-dihydro-4-[5-[(2-hydroxyethyl)sulphamoyl]-3,4-xylidino]-9,10-dioxoanthracene-2-sulphonate

EC Number:

247-269-2

EC Name:

Sodium 1-amino-9,10-dihydro-4-[5-[(2-hydroxyethyl)sulphamoyl]-3,4-xylidino]-9,10-dioxoanthracene-2-sulphonate

Cas Number:

25797-81-3

Molecular formula:

C24H23N3O8S2.Na

IUPAC Name:

sodium 1-amino-4-({3-[(2-hydroxyethyl)sulfamoyl]-4,5-dimethylphenyl}amino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

powder / dark blue

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: EN 01451.12

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2 to 3 kg
- Housing: The animals were housed individually in metal cages numbered by ear tags
- Diet: Standard rabbit food - NAFAG, No. 814, Gossau SG (ad libitum)
- Water: ad libitum
- Acclimation period: 4 d

ENVIRONMENTAL CONDITIONS
- Temperature: 22±2 °C
- Humidity: 55±10 %
- Photoperiod (dark / light): 12 h/12 h

Test system

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

other: polyethylene glycol (PEG 400) + saline (70 : 30 parts)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 mL (i.e. 500 mg)
- Concentration (if solution): 50 %

Duration of treatment / exposure:

24 h

Observation period:

7 d

Number of animals:

6 (i.e., 3 males and 3 females)

Details on study design:

TEST SITE:
- Before treatment the entire back and the flank of the rabbits were shaved with an electric clipper and immediately before treatment the shaven skin on one side was slightly scarified with the help of a "SchröpfSchnäpper", Aesculap, Switzerland.

EXPOSURE & OBSERVATIONS:
- Gauze patches of 2.5 x2.5 cm laden with 500 mg of the test substance were applied to the prepared abraded and intact skin.
- The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape. The dressings were removed after a 24 h application.
- The skin reaction was appraised upon removal and during an observation period of 7 d.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

(intact skin)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 4 d

Results 2

Irritation parameter:

erythema score

Remarks:

(intact skin)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 3 d

Results 3

Irritation parameter:

erythema score

Remarks:

(intact skin)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 4 d

Results 4

Irritation parameter:

erythema score

Remarks:

(intact skin)

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 3 d

Results 5

Irritation parameter:

erythema score

Remarks:

(intact skin)

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 4 d

Results 6

Irritation parameter:

erythema score

Remarks:

(intact skin)

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 3 d

Results 7

Irritation parameter:

edema score

Remarks:

(intact skin)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 4 d

Results 8

Irritation parameter:

edema score

Remarks:

(intact skin)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 9

Irritation parameter:

edema score

Remarks:

(intact skin)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 4 d

Results 10

Irritation parameter:

edema score

Remarks:

(intact skin)

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 11

Irritation parameter:

edema score

Remarks:

(intact skin)

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 4 d

Results 12

Irritation parameter:

edema score

Remarks:

(intact skin)

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Other effects:

none

Any other information on results incl. tables

Calculation of the primary skin irritation index:

 

MEAN REACTION SCORE
Time after exposure hours	e r y t h e m a		edema
	intact skin	abraded skin	intact skin	abraded skin
24	1.3	1.3	1.3	1.3
72	0.5	0.7	0.5	0.7
Total	1.8	2.0	1.8	2.0	7.6

Primary irritation index = 7.6 : 4 = 1.9

 

Due to intensive staining by the test substance erythema was not assessable. For the purpose of calculating the primary irritation index erythema was assumed to be equal to edema based on the correlation existing.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 20033/G was considered to be slightly irritating when applied to intact rabbit skin, however does not meet the EU CLP threshold for classification.

Executive summary:

An in vivo study was conducted to evaluate the skin irritation potential of the test substance (of ca. 82.2 % purity) in rabbits according to USEPA Guideline 163.81-5 which is similar to OECD Guideline 404 with few deviations. In this study, gauze patches of 2.5 x 2.5 cm laden with 0.5 g of the test material (i.e. 1 mL of a 50 % solution in polyethylene glycol (PEG 400) and saline (70 : 30 parts)) were applied to the prepared abraded and intact skin of rabbits for 24 h under occlusive conditions. After 24 h, the dressing was removed and the application sites were assessed for oedema and erythema. Further observations were conducted at 48, 72 h, 4 and 7 d. The exposure of FAT 20033/G to intact skin lead to slight irritation in terms of erythema and edema, however the scores obtained were below the mean critical threshold of 2.3 for all the exposed animals. The primary irritation score was calculated to be 1.9. Under the study conditions, the test substance was considered to be slightly irritating when applied to intact rabbit skin. However, responses were confirmed as not exceeding the EU CLP thresholds for triggering classification of skin irritant.