Pyrrolidinium, 1-[[(6R,7R)-7-amino-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-methyl-, chloride

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: Guideline study according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

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

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

477-080-2

EC Name:

-

Cas Number:

103121-85-3

Molecular formula:

C13 H19 N3 O3 S . HCl (Hill Formula) C13 H20 N3 O3 S . Cl (CAS Formula)

IUPAC Name:

477-080-2

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Name: MPI-ACA
Chemical name: Pyrrolidinium, 1-[(7 -amino-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl )methyl]-1-methyl-, chloride
Molecular formula: C13H19N3O3S.HCI
CAS No.: 103121-85-3.
Supplier: Sandoz GmbH
Batch-No. 49900408.
Appearance: White to yellowish powder.
Purity: 85.5 %
Solubility: Soluble in water: 120 g/L at 20 °C, poorly soluble in non-polar organic solvents
Melting point: 165 °C (decomposition).
pH = 2.86 (1% solution in deionised water, w/v)
Conditions of storage: In the refrigerator.
Stability at conditions of storage: Stable for 12 months.
Stability in aqueous solutions/suspensions: Not defined.
Date of expiry: 27 April 2008 (retest).
Date of receipt: 16 August 2007.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland
- Age at study initiation: Ca. 9 weeks.
- Weight at study initiation: 2.6, 1.9 and 1.9 kg
- Housing: Individual metal wire caging
- Diet: Ssniff K-H ad libitum
- Water): tap water via automatic watering system - ad libitum
- Acclimation period: at least 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean 19.3 to 20.0 °C
- Humidity (%): average of 62.4 to 65.7 %
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

Amount applied: 0.5 g test substance moistend with 1 mL deionised water, applied to an area of 25 x 25 mm.

Duration of treatment / exposure:

4 hours.

Observation period:

Rabbits observed at 1, 24, 48 and 72 hours after dressing removal. termination on Day 4

Number of animals:

3 females.

Details on study design:

Stepwise procedure:
First the test substance was administered to one animal. As no corrosive effect was observed, the test substance was administered
to two additional animals one week later.

Test site:
Area of exposure: 25 x 25 mm. Samples of the test substance were placed on gauze patches. They were held in place by fixing them marginally with non irritating tapes. The application sites were covered semi-occlusively by a dressing. Access by the animals to the application sites was prevented by a plastic collar.

Skin examinations:
The skins of the animals were examined for local alterations one day before the administration of the test substance (after clipping of the hair) and immediately before the administration. The treated areas of the animals were examined for erythema/eschar and oedema as well as for other local alterations (such as hyperplasia, scaling, discolouration, fissures, scabs and alopecia) approximately 1, 24, 48 and 72 hours after patch removal.

General examinations:
The animals were examined once daily for other than local changes of the skin.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

All areas treated with the test substance and all control areas were normal before the application and at each observation time.

Other effects:

General signs of toxicity:
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

All areas treated with the test substance and all control areas were normal before the application and at each observation time.

Executive summary:

A skin irritation test was performed according to OECD and EU test methods. Three female rabbits were exposed to MPI-ACA for 4 hours.

All areas treated with the test substance and all control areas were normal before the application and at each observation time. The test.substance is not a skin irritant.