Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate

Skin irritation / corrosion

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:

other: well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate

EC Number:

278-575-4

EC Name:

Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate

Cas Number:

76918-62-2

Molecular formula:

C18H13N3O3.Na

Details on test material:

- Name of test material (as cited in study report): Naphtolon-Natrium TRF 8

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, breeding colony
- Age at study initiation: 3 months to 5 months
- Weight at study initiation: 1,7 kg to 2,7 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Altromin 2123) ad libitum, appr. 15 g hay daily
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg mixed with 0.3 ml physiol. saline

Duration of treatment / exposure:

4 hours
at the end of the exposure period removal of test substance by washing with lukewarm tap water

Observation period:

72 h post removal of the patch

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch (Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
as in EU Method B.4, assessed approximately 30 - 60 min, 24, 48, and 72 h after the removal of the test item

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: # 1, 2, 3 each

Time point:

other: mean of 24, 48, and 72 h

Score:

0

Max. score:

4

Reversibility:

other: initial slight signs of irritation (erythema) were fully reversible within 24h

Results 2

Irritation parameter:

edema score

Basis:

animal: # 1, 2, 3 each

Time point:

other: mean of 24, 48, and 72 h

Score:

0

Max. score:

4

Reversibility:

other: no signs of irritation (edema) at any time

Irritant / corrosive response data:

Scores (edema or erythema) were 0 at 24, 48 and 72 h after removal of dressing in all animals.

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: expert judgment

Conclusions:

not irritating to skin

In an OECD guideline and GLP compliant primary skin irritation test in rabbits, Naphtolon-Natrium TRF 8 caused grade 0-1 erythema after 30-60 minutes, while neither erythema nor edema were observed 24, 48 and 72 hours after application of the test substance. Therefore, Naphtolon-Natrium TRF 8 can be regarded as not skin irritating.

Executive summary:

The primary skin irritation potential of the test item was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 30 - 60 min, 24, 48 and 72 hours after removal of the dressing. The mean scores were calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for edema grades, separately. The application of the test item to the skin resulted in mild, early-onset and transient signs of irritation such as erythema. These effects were reversible and were no longer evident 24 hours after treatment for all animals. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were reported. Thus, the test item did not induce significant or irreversible damage to the skin. Based upon these findings, the test item is considered to be "not irritating" to rabbit skin.