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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994
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:
1995
Report date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
(6R-trans)-7-amino-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
EC Number:
261-491-7
EC Name:
(6R-trans)-7-amino-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Cas Number:
58909-56-1
Molecular formula:
C12H13N5O5S2
IUPAC Name:
7-amino-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl}-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-ACT
Chemical name: (6R, 7R)-7-Amino-3-(2,5-dihydro-2-methyl-5-oxo-6-hydroxy-1,2,4-triazin-3-yl) thiomethyl-ceph-3-em-4-carbonic acid
CAS No.: 58909-56-1
Supplier: Biochemie Ges.m.b.H.
Batch No.: 3201530
Purity: 99.5 % (content related to waterfree substance)
Water content: 1.5 %
Impurities: Heavy metals: < 20 ppm, by-products: < 0.2 % each
Appearance: white powder
pH: 3.97 (1 % aqueous suspension, measured by pH-meter)
Stability of the test substance: stable under conditions of storage
Disintegration: from 180 *C on
Storage: in a refrigerator in the dark
Date of handing over: July 26, 1994



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. A-2325 Himberg. Austria
- Age at study initiation: Ca. 8 w.
- Weight at study initiation: mean of 210 g for males; mean of 171 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 20 mL per kg body weight.
Administration was performed with freshly prepared test substance suspensions. 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
Statistics:
No.

Results and discussion

Effect levels
Sex:
male/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: All animals did not show any clinical signs during the entire observation period.
Body weight:
Body weights: Body weight and body weight gain was inconspicuous in all animals.
Gross pathology:
Necropsy findings: No abnormal findings were made in the animals at the necropsy 14 d p.a..

Any other information on results incl. tables

No 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.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No 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. The LD50 is >2000 mg/kg body weight.
Executive summary:

The standard acute oral toxicity method according to the EU- and OECD-guidelines was applied. 7 -ACT 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 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.