Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
data is from experimental reports

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
To assess the dermal irritation potential of 4-nitrobenzene-1,3-diamine in rabbits
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material : 4-Nitro-m-phenylenediamine
- Molecular formula : C6H7N3O2
- Molecular weight : 153.14 g/mol
- Smiles notation : c1(c(cc(N)cc1)N)[N+](=O)[O-]
- InChl (if other than submission substance): 1S/C6H7N3O2/c7-4-1-2-6(9(10)11)5(8)3-4/h1-3H,7-8H2
- Substance type: Organic
- Physical state: Solid
Specific details on test material used for the study:
- Name of test material : 4-Nitro-m-phenylenediamine
- Molecular formula : C6H7N3O2
- Molecular weight : 153.14 g/mol
- Smiles notation : c1(c(cc(N)cc1)N)[N+](=O)[O-]
- InChl (if other than submission substance): 1S/C6H7N3O2/c7-4-1-2-6(9(10)11)5(8)3-4/h1-3H,7-8H2
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hacking & Churchill ltd, Huntingdon, UK
- Age at study initiation: Not reported
- Weight at study initiation: average about 3 kg
- Housing: The animals were housed individually
- Diet (e.g. ad libitum): "muemmel Z-222" (Hoeing Kraftfutterwerk Lower Saxony, Verden / Aller), ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 40-50%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hours light / dark cycle (artificial lighting. 7 - 19 h)

IN-LIFE DATES: From: To: Not reported

Test system

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes
Amount / concentration applied:
0.5 g of creamed with water test substance were applied.
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 h after removal of the lobules and conclusion of the test after 10 test day.
Number of animals:
3 male animals
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: full
- Type of wrap if used: Gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours

SCORING SYSTEM: As per the method of Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hrs
Score:
1.3
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0.3
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
After one hour, a yellowish discoloration of the skin was found. Discoloration held until the 9th day of the experiment at (Animal No. 4). The animals were followed up until the 10th day of the experiment,

Any other information on results incl. tables

Time after patch removal

Skin irritation Animal No.

Total

Average

3

4

5

Erythema

1 hr

1

3

1

-

-

24 hr

1

2

1

4

1.3

48 hr

1

2

1

-

-

72 hr

1

1

0

2

0.7

Experimental end

0

0

0

-

-

 

Edema

1 hr

0

0

0

-

-

24 hr

0

0

0

0

0

48 hr

0

0

0

-

-

72 hr

0

0

0

0

0

Experimental end

0

0

0

-

-

The sum of the average stimulus values after 24 h (erythema = 1.3, edema = 0) and 72 h (erythema = 0.7, edema = 0) obtained by dividing by the number of these time points (by 2) gave a primary irritation score of 1.0

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The sum of the average stimulus values after 24 h (erythema = 1.3, edema = 0) and 72 h (erythema = 0.7, edema = 0) obtained by dividing by the number of these time points (by 2) gave a primary irritation score of 1.0.
From the above results, the classification of 4-nitro-m-phenylene diamine was considered to be irritating according to the E.C Commission's proposal on criteria for effects and irritants as set out in Annex VI II B 6 Directive.
Executive summary:

The primary skin irritation of 4-nitro-m-phenylenediamine was assessed in a study conducted on rabbits as per OECD Guideline 404.

The flank skin of 3 male New Zealand White rabbits was depilated on both sides on an area of approximately 6 x 6 cm with an electric clipper with suction for 24 hours before starting the test. In the experiment only animals with intact skin were taken. 0.5 g of 4 -nitro-m-phenylenediamine was applied under occlusion to clipped intact skin of the flank. The untreated side served as a control.The survey findings was performed 1, 24, 48 and 72 h after removal of the lobules and conclusion of the test after 10 test day. The stimulus values ​​after 24 and 72 h were averaged over the experimental animals and dividing the resultant sum of the averages by 2.

After one hour, a yellowish discoloration of the skin was found. Discoloration held until the 9th day of the experiment at (Animal No. 4). The animals were followed up until the 10th day of the experiment.

The sum of the average stimulus values after 24 h (erythema = 1.3, edema = 0) and 72 h (erythema = 0.7, edema = 0) obtained by dividing by the number of these time points (by 2)  gave a primary irritation score of 1.0.

From the above results, the classification of 4-nitro-m-phenylene diamine was considered to be irritating according to the E.C Commission's proposal on criteria for effects and irritants as set out in Annex VI II B 6 Directive.