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Toxicological information

Acute Toxicity: oral

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
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

Constituent 1
Chemical structure
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:
1-{[(6R,7R)-7-amino-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl}-1-methylpyrrolidin-1-ium chloride
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.