(6S,7S)-7-Amino-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

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: Guideline study with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

435-680-1

EC Name:

-

Cas Number:

24701-69-7

Molecular formula:

C9H12N2O4S (Hill formula) C9H12N2O4S (CAS formula)

IUPAC Name:

(6R,7R)-7-amino-3-(methoxymethyl)-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: 7-AMCA
Chemical name: (6R, 7R)-7-Amino-3-methoxymethyl-ceph-3-em-4-carbonic acid
CAS No.: 24701-69-7
Supplier: Sponsor
Batch No.: 8701633
Purity: 96.6 % (content related to water free substance)
Water content: 0.3 %
Appearance: white powder
pH: 3.95 of a 1 % aqueous suspension
Conditions of storage: Refrigerator, in the dark
Stability: Stable under conditions of storage

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Forschungsinstitut für Versuchstierzucht. Himberg. Austria..
- Age at study initiation: Ca. 8 w.
- Weight at study initiation: mean of 213 g for males; mean of 172 g for females.
- Fasting period before study: From the evening before dosing to 3 h after dosing.
- Housing: Single caging
- Diet: Altromin 1314 forte ad libitum
- Water: Tap water ad libitum
- Acclimation period: 6 d.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 22
- Humidity (%): ca. 55
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

A peroral administration was performed once in the morning by stomach intubation using a metal gavage. The dose volume was 10 mL per kg body weight. The test substance solution was stirred during the time of administration.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males + 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 5 times on the first day, then at least once each day.
- Frequency of weighing: before administration, 7 and 14 d p.a.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: Number of deaths: 0
Female: Number of deaths: 0

Clinical signs:

Signs of toxicity related to dose levels: No relevant clinical signs for systemic toxicity were observed.

Body weight:

Body weights: Body weight and body weight gain was inconspicuous in all animals.


Necropsy findings: No abnormal findings were made in the animals at the necropsy 14 d p.a., except for one: In the affected female coverings on glandular stomach mucosa and on spleen surface were found.

Gross pathology:

Necropsy findings: No abnormal findings were made in the animals at the necropsy 14 d p.a., except for one: In the affected female large adrenal glands were observed.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50,oral,rats is higher than 2000 mg/kg body weight.

Executive summary:

The standard acute oral toxicity method according to the EU- and OECD-guidelines was applied. The substance was administered by gavage in a limit dose of 2000 mg/kg body weight to 5 male and 5 female rats.

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