3-acetoxymethylen-7-amino-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

Study period:

September 19, 1994 to November 30, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study (OECD 401) with acceptable restrictions.

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:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

EC Number:

213-485-0

EC Name:

3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Cas Number:

957-68-6

Molecular formula:

C10H12N2O5S

IUPAC Name:

(6R,7R)-3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Test material form:

solid - liquid: suspension

Details on test material:

- Name of test material (as cited in study report): 7-ACA
- Physical state: white powder
- Analytical purity: 95%-102% (HPLC)
- Impurities: 7-ACA 4.7%
- Batch No.: 3701586
- Expiration date of the batch: stable under conditions of storage
- Storage condition of test material: in a refrigerator in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals:
Supplier: Forschungsinstitut für Versuchstierzucht, A-2325 Himberg
Age: approximately 8 weeks at time of administration
Environment:
Room temperature: average of 22 °C,
Humidity: average of 55 %,
Air exchange: 12 per hour,
Light artificial light from 6 a.m. to 6 p.m.,
Cages: Single caging in Makrolon cages type III,
Bedding material: Aspen wood chips, type "4 HV",
Feed: Altromin 1314 ff, gamma irradiated with 10 kGy 60Co, ad libitum,
Water: tap water, offered in Makrolon bottles with stainless steel canules, ad libitum,
Acclimatization: 6 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Carboxymethylcellulose, sodium salt

Details on oral exposure:

Peroral administration was performed within maximum 30 minutes after preparation of the test substance suspension once in the morning by stomach intubation using a metal gavage. The test substance suspension was stirred during the time of administration.

Doses:

2000 mg/kg body weight (20 ml/kg)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

Observations in life: Behaviour, reactions and physical signs of the animals were observed 0-0.5, >0.5-1, >1-2, >2-4 and >4-6 hours after administration of the test substance (p.a.) and then at least once a day for a total of 2 weeks.

Body weight and body weight gain: Body weight was determined before administration, 7 days p.a. and 14 days p.a.
Body weight gain was calculated for each week of the study, i.e. 0-7 d p.a. and 7-14 d p.a.

Necropsy: All animals were sacrified by CO2 14 days p.a. and examined macroscopically in an attempt to detect possible residual lesions.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals (5 males and 5 females) survived until the scheduled termination of 14 days p.a.

Clinical signs:

other: Males: 3/5 animals were normal during the whole obser vation period. In the affected males chromodacryorrhoea, an unspecific sign of general malaise, was noted on day of administration of the test substance for about 2 hours. Females: All animals, i.e. 5

Gross pathology:

Males and females: All animals were normal at terminal necropsy.

Other findings:

Sex differences: Signs in life and post mortem findings revealed no differences between the sexes in the response to the test substance.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information

Conclusions:

All animals survived until the scheduled termination.
No signs of toxicity were observed in life or post mortem.
No difference between the sexes was noted in the response to the test substance.
The LD50 (oral) in rats of both sexes is higher than 2000 mg of "7-ACA" per kg body weight.