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Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 14 Mar 1977 to 18 Mar 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study according to FDA guideline
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: FDA, Fed. Reg. 38, No. 187, 27.9.1973, p.27019
Deviations:
no
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5-methyl-2-(p-tolyl)-3H-pyrazol-3-one]
EC Number:
239-898-6
EC Name:
4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5-methyl-2-(p-tolyl)-3H-pyrazol-3-one]
Cas Number:
15793-73-4
Molecular formula:
C34H28Cl2N8O2
IUPAC Name:
4,4'-[(3,3'-dichlorobiphenyl-4,4'-diyl)didiazene-2,1-diyl]bis[5-methyl-2-(4-methylphenyl)-2,4-dihydro-3H-pyrazol-3-one]
Test material form:
solid: nanoform

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.5-2.0 kg
- Housing: individually
- Diet (ad libitum): ERKA 8300 (Futtermittelwerke Robert Koch, Hamm, Germany), ad libitum
- Water (ad libitum): tap water, ad libitum

ENVIRONMENTAL CONDITIONS
no data

Test system

Type of coverage:
occlusive
Preparation of test site:
other: one site shaved, one site shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
24 h (no rinsing after removal of coverage)
Observation period:
24, 48 and 72 h after application
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: flank, each site 3 x 3 cm
- Type of wrap if used: PVC film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to FDA guideline
Erythema:
0: no erythema
1: very light erythema, barely perceptible
2: well defined erythema
3: moderate to severe edema
4: severe erythema (beet redness) to slight eschar formation (injuries in depth)

Edema:
0: no edema
1: very slight, barely perceptible edema
2: slight edema (edges of area well defined by definite raising
3: moderate edema, raised approx. 1 mm
4: severe edema (raised more than 1 mm and extending beyond area of exposure

Values for erythema and eschar formation at 24 and 72 h post application on intact and abraded skin each (4 values) have to be added.
Values for edema formation at 24 and 72 h post application on intact and abraded skin each (4 values) have to be added.
The total of eight values is divided by four, yielding the primary irritation index.

0-0.5: non irritant
0.6-3.0: slightly irritant
3.1-5.0: moderately irritant
5.1-8.0: severely irritant

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
other: 24 h exposure duration, observation time points: 48 and 72 h after start of exposure (24 h post application no examination of erythema was possible due to intensive staining of the application site)
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
other: 24 h exposure duration, observation time points: 48 and 72 h after start of exposure (24 h post application no examination of erythema was possible due to intensive staining of the application site)
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
other: 24 h exposure duration, observation time points: 48 and 72 h after start of exposure (24 h post application no examination of erythema was possible due to intensive staining of the application site)
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
other: 24 h exposure duration, observation time points: 48 and 72 h after start of exposure (24 h post application no examination of erythema was possible due to intensive staining of the application site)
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
other: 24 h exposure duration, observation time points: 48 and 72 h after start of exposure (24 h post application no examination of erythema was possible due to intensive staining of the application site)
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: 48, 72 h
Score:
0
Max. score:
4
Remarks on result:
other: 24 h exposure duration, observation time points: 48 and 72 h after start of exposure (24 h post application no examination of erythema was possible due to intensive staining of the application site)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
- 24 h post application no examination of erythema was possible due to intensive staining of the application site; no erythema were detectable at any later time point
- no edema were observed at any time point
- identical results were obtained with intact and scarified skin

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the test item was not irritating to the skin of rabbits.

This conclusion is legitimated even though the applied testing regime differs from today's standard methods. Since the test conditions were more stringent than required by OECD 404 (i.e. 24 treatment, occlusive coverage, and scarified skin instead of 4 h treatment, semi-occlusive coverage, and intact skin) the test results are considered adequate to fulfill the endpoint requirements.
Executive summary:

6 New Zealand White rabbits were dermally exposed to 500 mg of the test item for 24 h on shaved intact and abraded skin under occlusive conditions. Obervations were performed 24, 48 and 72 h after start of exposure. Twenty four hours after application no examination of erythema was possible due to intensive staining of the application site. No signs of irritation (edema and erythema score 0) were observed on the intact or abraded skin. Under the conditions of this study the test item was not irritating to the skin of rabbits.