Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles. Conducted prior to implementation of OECD and GLP guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: FDA guideline (§ 1500.41, Fed. Reg. Vol. 38, No. 187, p. 27019, 1973)
GLP compliance:
no
Remarks:
conducted prior to GLP guideline implementation

Test material

Constituent 1
Chemical structure
Reference substance name:
4'-chloro-3-hydroxy-2-naphthanilide
EC Number:
202-189-7
EC Name:
4'-chloro-3-hydroxy-2-naphthanilide
Cas Number:
92-78-4
Molecular formula:
C17H12ClNO2
IUPAC Name:
N-(4-chlorophenyl)-3-hydroxynaphthalene-2-carboxamide

Test animals

Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG breeding colony
- Strain: SPF-Albino-Himalayan, Hoe HIMK(SPFWiga)
- Weight at study initiation: 1,5 - 2,0 kg
- Housing: single cage
- Diet: ERKA 8300, ad libitum
- Water: tap water, ad libitum

Test system

Type of coverage:
occlusive
Preparation of test site:
other: clipped intact and clipped scarified
Vehicle:
other: propandiol 1,2
Controls:
not required
Amount / concentration applied:
0.5 g mixed with 0.6 ml propandiol 1,2
Duration of treatment / exposure:
24 h
Observation period:
72 h after beginning of treatment
Number of animals:
6
Details on study design:
0.5 g of the test substance mixed with 0.35 ml propandiol 1,2 and placed on a square gauze patch, 2,5 x 2,5 cm of size, was applied on a clipped/intact and clipped/scarified skin of the albino rabbit. The patches were fixed by an adhesive tape and additionally covered by a neutral, impermeable PVC film. The entire trunk of the animal was then wrapped with an elastic bandage. After 24 hours of exposure the patches were removed and the reactions were examined. Follw-up examinations were made 48 h and 72 h after beginning of treatment.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean of 24, 48, 72 h after beginning of treatment
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h after beginning of treatment (end of observation)
Remarks on result:
other: shaved intact
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean of 24, 48, 72 h after beginning of treatment
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 h after beginning of treatment (end of observation)
Remarks on result:
other: shaved intact
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean of 24, 48, 72 h after beginning of treatment
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant because of lacking effects
Remarks on result:
other: shaved intact
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: mean of 24, 48, 72 h after beginning of treatment
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Remarks:
72 h after beginning of treatment (end of observation)
Remarks on result:
other: shaved intact
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: mean of 24, 48, 72 h after beginning of treatment
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h after beginning of treatment (end of observation)
Remarks on result:
other: shaved intact
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: mean of 24, 48, 72 h after beginning of treatment
Score:
0
Max. score:
4
Reversibility:
other: reversibility not relevant because of lacking effects
Remarks on result:
other: shaved intact
Irritation parameter:
edema score
Basis:
animal: # 1-6 each
Time point:
other: mean of 24, 48, 72 h after beginning of treatment
Score:
0.06
Max. score:
4
Reversibility:
fully reversible within: 24 h after patch removal
Remarks on result:
other: shaved intact
Irritant / corrosive response data:
Based on the slightness and the full recovery in the majority of test animals a full reversibility of effects is expected for the remaining animal in the case of a prolonged observation period of 14 days according to effective guidelines.

Similar results were obtained for clipped scarified skin.
Other effects:
no other effects reported

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Classification acc. to (EC) 1272/2008: not irritating

This conclusion is legitimate even though the applied testing regime differs from today's standard methods. Since the test conditions were more stringent than required by OECD TG 404 (i.e. 24 h 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:

The test material was tested for skin irritancy according to FDA guideline. Both intact and scarified skin sites of six rabbits were exposed to 0.5 g test substance for 24 h under occlusive conditions and the skin responses were examined at 24, 48, and 72 h after beginning of treatment. Mean values of the 24, 48 and 72 h readings were calculated for each animal. Only slight effects (erythema mean score: <=1, edema mean score: 0.06) below the threshold for classification were determined for the intact skin. All effects were fully reversible or expected to be fully reversible. Similar results were obtained for scarified skin. Based on these findings the test material was judged not to be irritating to skin.