3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 31, 1994 - October 18, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study (OECD 404) with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

EC Number:

213-485-0

EC Name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Cas Number:

957-68-6

Molecular formula:

C10H12N2O5S

IUPAC Name:

(6R,7R)-3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): 7-ACA
- Physical state: white powder
- Analytical purity: 95%-102% (HPLC)
- Impurities: 7-ACA 4.7%
- Batch No.: 3701586
- Expiration date of the batch: stable under conditions of storage
- Storage condition of test material: in a refrigerator in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals:
Supplier: Charles River Wiga GmbH, D-97633 Sulzfeld
Number ans sex: 3 females

Animal maintenance:
Room temperature: average of 19.5 °C
Relative humidity: average of 50 %
Air exchange: 12 per hour
Light: artificial light from 6 a.m. to 6 p.m.
Cages: individual caging in metal wire cages. Ehret GmbH, D-79312 Emmendingen, type KK 016R
Feed: Altromin 2023 diet for rabbits, ad libitum
Water: tap water from an automatical watering system, ad libitum
Identification: labelling with felt-tipped pen in the ear
Acclimatization: 6 days

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

A cellulose patch with 0.5 g of the test substance, spread over an area of approximately 6x2 cm and soaked with 1.5 ml distilled water, was applied to the test site and held in place by fixing marginally with non irritating tape.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after patch removal

Number of animals:

3

Details on study design:

Procedure: Hair was clipped on the dorsal area of the trunk one day before the application of the test substance. The test site was median on the dorsal thoracal region.
A cellulose patch with 0.5 g of the test substance, spread over an area of approximately 6x2 cm and soaked with 1.5 ml distilled water, was applied to the test site and held in place by fixing marginally with non irritating tape. The application site was covered by a dressing.
Access by the animal to the application site was prevented by a plastic collar.
The duration of exposure was 4 hours.
At the end of the exposure period the dressing, the tape with the patch and the collar were removed. Residual test substance was wiped off using wet cellulose tissue.

Clinical examination and scoring:
Animals were examined for erythema/eschar and oedema as well as for other local and systemic signs approximately 1, 24, 48 and 72 hours after patch removal.
No additional examinations were performed.
The skin was examined using a cold light source KL 1500 electronic.
Dermal irritation was scored and recorded.

General examinations: At all observation times the animals were examined for other than local changes.

Results and discussion

In vivo

Results

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours after patch removal

Score:

0

Max. score:

0

Irritant / corrosive response data:

Erythema/eschar: In all animals only scores of "0" were noted at reading times.
Oedema: In all animals only scores of "0" were noted at reading times.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the EC-guideline 91/325 a test substance is considered to cause dermal irritation ("R38"), if a mean score of "2.0" or more for erythema/eschar or for oedema formation (calculated from the reading times, i.e. 24, 48 and 72 hours after the end of exposure) is observed in at least 2/3 animals.
The following mean scores were calculated for the individual examinations:
Erythema/eschar: "0.0" in all animals.
Oedema: "0.0" in all animals.
Therefore, the test substance "7-ACA" does not require the risk phrase "R38 - Irritating to skin".