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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: A study according to the EU and OECD methods, including 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:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye 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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Germany
- Age at study initiation: ca. 9 weeks.
- Weight at study initiation: 2.3 - 2.4
- Housing: single caging
- Diet: SNIFF K-H ad libitum
- Water: Tap water ad libitum
- Acclimation period: >= 12 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 19.2
- Humidity (%): average of 61.7
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Equivalent to 0.1 mL: 16 to 18 mg.

Duration of treatment / exposure:

Once.

Observation period (in vivo):

1, 24, 48, 72 h and 7 d p.a.

Number of animals or in vitro replicates:

3.

Details on study design:

Prior to starting the eye irritation/corrosion study the pH-value of the test substance was determined. Substances with a pH < 2.0 and pH > 11.5 need not to be tested for acute eye irritation/corrosion.
The test substance was administered first to one animal. As no evidence for a serious damage to the eye of this animal was found during the initial 72 hour observation period (no corrosive effect), the test substance was administered to the other two animals subsequently.

The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs for instillation. The eyes were held closed for about one second to prevent a loss of test substance. The left eyes remained untreated and served as a control.
The whole eyes, especially the corneae, the irises and the conjunctivae were examined, using an otoscope lamp.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

The untreated eyes ("control eyes") were normal at each observation time.
The eyes, treated with the test substance ("test eyes") were normal before the instillation. After the instillation of the test substance, the following findings were made:
Corneae: Not affected at any examination term.
Irises: Not affected at any examination term.
Conjunctivae, redness: A score of "1" in all animals from 1 h p.a. until a maximum of 24 h p.a.
Conjunctivae, chemosis: A score of "1" in 2/3 animals only 1 h p.a.

Other effects:

No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.
The untreated eyes ("control eyes") were normal at each observation time.

Any other information on results incl. tables

For details of the results see the attachment.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Only slight irritations of the conjunctivae were observed at 1 and 24 h p.a. The substance is not classified as irritant.

Executive summary:

Eye irritation was investigated according to the EU- and OECD-methods. The equivalent of 0.1 mL of the test substance was instilled into the conjunctival sac of one eye of each of 3 New Zealand White rabbits. Results:

Corneae and irises: Not affected at any observation point.

Conjunctivae, redness and chemosis: slight irritations were observed at 1 and 24 h p.a, returning to normal afterwards. The substance is not classified as irritant.