Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from January to February 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Oestr-5(10)-ene-3,17-dione
EC Number:
223-564-1
EC Name:
Oestr-5(10)-ene-3,17-dione
Cas Number:
3962-66-1
Molecular formula:
C18H24O2
IUPAC Name:
(3aS,3bR,9bS,11aS)-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,6H,7H,8H,9H,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-dione

Test animals

Species:
rat
Strain:
other: Jcl:SD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CLEA Japan, Inc.
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 84-92 g (males), 97-98 g (females)
- Fasting period before study: 19 hours
- Housing: 1 animal/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.085% Myrj® 53 + 0.9% NaCl in water
Details on oral exposure:
- Application volume: 2.0 ml/100g bw
- Application concentration: 100 mg/ml
- Rationale for the selection of the starting dose:
Dose levels of 2000, 200 and 25 mg/kg were set in accordance with the acute toxic class method
(OECD guideline no. 423). The LD50 in rats after oral administration of dienogest, the final
product of ZK 67026, is >2000 mg/kg. The LD50 of ZK 5397 (4-Estrene-3,17-dione) the
structure of which resembles that of ZK 67026, is between 200 mg/kg and 2000 mg/kg (probably
near 2000 mg/kg). Since the toxic potential of ZK 67026 is supposed to be not high, in Step I,
2000 mg/kg was administered in males. In Step II, 2000 mg/kg was administered in females
since there were no deaths in males after administration. The lower doses were not administered,
since no deaths were observed in either males or females at 2000 mg/kg.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weighing)
- Necropsy of survivors performed: yes
Statistics:
none (limit test)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
other: LD50 cut-off
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died.
Clinical signs:
No compound-related findings were observed in any of the animals.
Body weight:
No compound-related effects were observed.
Gross pathology:
No compound-related findings were found out.

Applicant's summary and conclusion

Executive summary:

A single oral administration of the test substance by gavage to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, clinical findings, effects on body weight gain and gross pathological findings. According to OECD TG 423 the oral LD50 of the test substance is therefore > 2000 mg/kg body weight.