2-(4-aminoanilino)-5-nitrobenzenesulphonic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from National Technical Reports library (NTRL)

Data source

Reference

Reference Type:

grey literature

Title:

Delayed Contact Hypersensitivity in Guinea Pigs

Author:

National Technical Reports library (NTRL)

Year:

1991

Bibliographic source:

National Technical Reports library (NTRL),AMER CYANAMID CO, Microfiche Number: OTS0534436,1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

To determine if a Dapsone causes delayed hypersensitivity in guinea pigs as determined by the measurement of skin reactivity.

GLP compliance:

not specified

Type of study:

patch test

Justification for non-LLNA method:

not specified

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'-Diaminodiphenyl Sulphone

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): FXM-355 (Dapsone)
- Molecular formula (if other than submission substance): C12H12N2O2S
- Molecular weight (if other than submission substance): 248.301 g/mol
- Substance type: Organic
- Physical state: Solid
- Purity: no data
- Impurities (identity and concentrations): no data

Specific details on test material used for the study:

- Name of test material (as cited in study report): FXM-355 (Dapsone)
- Molecular formula (if other than submission substance): C12H12N2O2S
- Molecular weight (if other than submission substance): 248.301 g/mol
- Substance type: Organic
- Physical state: Solid
- Purity: no data
- Impurities (identity and concentrations): no data

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Perfection Breeders, Douglassville, Pennsylvania
- Age at study initiation:
- Weight at study initiation: 300 - 500 gm
- Housing: Guinea pigs were housed two per cage in wire metal cages. Waste material removed daily. Cages and feeders
sanitized weekly.
- Diet (e.g. ad libitum): Wayne Guinea Pig Diet, ad libitum, food was checked
daily and added or replaced as needed. Feeders were designed to reduce soiling, bridging and scattering.
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: five (5) days

ENVI\RONMENTAL CONDITIONS
- Temperature (°C): 20°C +- 30°C
- Humidity (%):30-70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

other: DNCB (0.3%) - Ethanol (80%)

Concentration / amount:

100%

Day(s)/duration:

14 days

Adequacy of induction:

not specified

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: DNCB (0.3%) - Ethanol (80%)

Concentration / amount:

100%

Day(s)/duration:

No data

Adequacy of challenge:

not specified

No. of animals per dose:

Test article – twenty (20)
Positive Control – ten (10)
Naive challenge – four (4)
Dose-range - four (4)

Details on study design:

RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: six hours
- Test groups: twenty (20) guinea pig
- Control group: Positive Control – ten (10)
- Site: 4 sites
- Frequency of applications: once a week for three weeks, a total of three six-hour
Inductions.
- Duration: 30 days
- Concentrations: 400 mg/ induction site (100%)

B. CHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: 14 days after
- Exposure period: 30 min
- Test groups: twenty (20) guinea pig
- Control group: Positive Control – ten (10)
- Site: naive site on the left side
- Concentrations: 400 mg
- Evaluation (hr after challenge): 24. 48 hrs

OTHER: Local and systemic effects W8re
observed.

Positive control substance(s):

yes

Remarks:

1-Choloro-2,4-dinitrobenzene

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin reaction were observed

Remarks on result:

no indication of skin sensitisation

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin reaction were observed

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

Delayed Contact Hypersensitivity in Guinea Pigs

Incidence and Severity of Responses at Challenge

	Naive Site
	24 hours		48 hours
Test Article	Incidence	Severity	Incidence	Severity
FXM-355 (100 %)	0/17	0.1	0/17	0
Naive Animals FXM-355 (100 %)	0/4	0	0/4	0
DNCB (0.3%)	9/9	2.4	9/9	2.6

Applicant's summary and conclusion

Interpretation of results:

other: Noit sensitizing

Conclusions:

No positive responses were observed in guinea pig receiving dapsone at a 100 % concentration at 24 or 48 hours after the challenge. Dapsone did not cause hypersensitivity in quinea piqs.
Hence Dapsone is not sensitizer o the skin of Guinea pig.

Executive summary:

In a preliminary dose-range finding study, four animals (two males and two females) were exposed to one concentration (as received) of Dapsone at four skin sites. Based upon the results of the dose-range finding study, the dose chosen for induction was 100 %.

Dapsone was dermally applied to twenty guinea pigs (ten males and ten females for a total of three six-hour insult periods at a 100 % concentration.

An additional group of ten guinea pigs (five males and five females) was treated with 1-chloro-2,4-dinitrobenzene at 0.3% concentration for a total of three six-hour insult periods. Fourteen days after the last induction period, all animals were challenged at a naive site. A positive response was elicited

in the animals receiving the positive control article, 1-chloro-2,4-dinitrobenzene (DNCB).

Redness and edema scores in all animals at 24 and 48 h recorded after each treatment and at 24 and 48 h after the challenge.

No positive responses were observed in guinea pig receiving dapsone at a 100 % concentration at 24 or 48 hours after the challenge. Dapsone did not cause hypersensitivity in quinea piqs.

Hence Dapsone is not sensitizer to the skin of Guinea pig.