Dapsone

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 01 November 2016 and 04 November 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

28 July 2015

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

EC 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Dapsone

EC Number:

201-248-4

EC Name:

Dapsone

Cas Number:

80-08-0

Molecular formula:

C12H12N2O2S

IUPAC Name:

4,4'-sulfonyldianiline

Test material form:

solid: particulate/powder

Remarks:

White powder

Details on test material:

Dapsone, pharmaceutical grade (4,4-DDS)

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Hsdlf:NZW strain

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Leicestershire, UK.
- Age at study initiation: 15 - 52 weeks
- Weight at study initiation: 4.09 - 4.11 kg
- Housing: individually housed in suspended cages
- Diet (e.g. ad libitum): ad libitum (2930C Teklad Global Rabbit diet supplied by Envigo RMS (UK) Limited, Oxon, UK)
- Water (e.g. ad libitum): adlibitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23”C
- Humidity (%): 30 - 70%
- Air changes (per hr): >15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 01 November 2016 To: 04 November 2016

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

Clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

On the day of the test a suitable test site was selected on the back of each rabbit. At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 mL of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

2

Details on study design:

Study Design
On the day before the test each of a group of two rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 mL of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale below (Ta ble 1).:

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Data Evaluation
The scores for erythema and edema at the 24 and 72 Hour readings were totaled for the two test rabbits (8 values) and this total was divided by 4 to give the primary irritation index of the test item. The test item was classified according to the following scheme devised by Draize, J.H. (1959):
Primary Irritation Index Classification of Irritancy
0 Non-irritant
> 0 to 2 Mild irritant
> 2 to 5 Moderate irritant
> 5 to 8 Severe irritant
If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test item is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.
The results were also evaluated according to the Globally Harmonized System of Classification and Labelling of Chemicals.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #1

Time point:

72 h

Score:

<= 0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #2

Time point:

72 h

Score:

<= 0

Max. score:

0

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No evidence of skin irritation was noted during the study

Other effects:

One animal showed body weight loss and the other animal showed expected gain in body weight during the study.

Any other information on results incl. tables

Individual Skin Reactions:

Skin Reaction	Observation Time (following patch removal)	Individual Scores		Total
		75628 Female	75629 Female
	Immediately	0	0	(0)
Erythema/Eschar Formation	1 Hour	0	0	(0)
	24 Hours	0	0	(0)
	48 Hours	0	0	(0)
	72 Hours	0	0	(0)
	Immediately	0	0	(0)
Edema Formation	1 Hours	0	0	(0)
	24 Hours	0	0	(0)
	48 Hours	0	0	(0)
	72 Hours	0	0	(0)

 Sum of 24 and 72 Hour Readings (S) :  0

 Primary Irritation Index (S/4)              :  0/4 = 0.0

 Classification                                    :  MILD IRRITANT    

                    

  Individual Body Weights and Body Weight Changes:

Rabit Number and Sex	Individual Body Weight (kg)		BOdy Weight Change (kg)
	Day 0	Day 3
75628 Female	4.11	4.18	0.07
75269 Female	4.09	4.06	-0.03

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item produced a primary irritation index of 0.0 and was classified as non irritant to rabbit skin according to the Draize classification scheme. The test item does not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals.

Executive summary:

The study was performed accoring to OECD TG 404 Acute Dermal Irritation/Corrosion and Method B4 Acute toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008, to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. A single 4 Hour, semi occluded application of the test item to the intact skin of two rabbits produced no evidence of skin irritation. The test item produced a primary irritation index of 0.0 and was classified as non irritant to rabbit skin according to the Draize classification scheme. The test item does not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals.