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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

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:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland.
- Age at study initiation: Ca. 8 w.
- Weight at study initiation: 171 - 196 g
- Fasting period before study: From the evening before dosing to 3 h after dosing.
- Housing: Single caging
- Diet: SNIFF R/M-H ad libitum
- Water: Tap water ad libitum
- Acclimation period:At least 5 d.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 22
- Humidity (%): ca. 64
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

A peroral administration was performed once in the morning by stomach intubation using a metal gavage.
The dose volume was 20 mL per kg body weight. The individual dose volumes were calculated using the body weights determined on the day of the administration.

Doses:

300 and 2000 mg/kg bw. See below.

No. of animals per sex per dose:

3 rats per step.

Control animals:

no

Details on study design:

The sequence of dosing of the test substance was:
Step 1: 300 mg/kg bw.
Step 2: 300 mg/kg bw.
Step 3: 2000 mg/kg bw.
Step 4: 2000 mg/kg bw.

Statistics:

No.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality: All animals survived until the scheduled termination of the study.

Clinical signs:

Observations in life. The findings, with an onset shortly after the administration and lasting until 6 h p.a. were:
Signs of reduced well-being. This term encompasses unspecific alterations, like sedation, apathy, piloerection, hunched posture or closed eyes, in single or multiple occurrence.

Body weight:

Body weights: All animals gained weight in both weeks p.a.

Gross pathology:

Necropsy findings: No abnormal findings were made in all animals at the necropsy 14 d p.a.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No severe toxic effects of the test substance were noted by signs in life and post mortem at a dose of 2000 mg test substance per kg body weight. No mortality occurred.

Executive summary:

The acute toxic class (ATC) method according to the EU- and OECD-guidelines was applied to investigate the acute oral toxicity of MPI-ACA in rats.

No severe toxic effects of the test substance were noted by signs in life and post mortem at a dose of 2000 mg test substance per kg body weight. No mortality occurred. The oral LD50 was determined to >2000 mg/kg body weight.