Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Rats (3/sex/group) received test substance orally over 5 days once daily. The effects were evaluated using clinical observation and liver enzymes (GOT, GPT, APL). Blood samples were taken on day 6. Thereafter all animals were retained 9 - 11 days without treatment to look for reversibility of effects. Finally all animals were sacrificed and necrospied.
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Progesterone
EC Number:
200-350-6
EC Name:
Progesterone
Cas Number:
57-83-0
Molecular formula:
C21H30O2
IUPAC Name:
(1S,3aS,3bS,9aR,9bS,11aS)-1-acetyl-9a,11a-dimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
Details on test material:
- Name of test material (as cited in study report): progesterone
- Lot/batch No.: 54234184
- Expiration date of the lot/batch: Nov 1998

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: physiol. saline + 0.085% Myrj53
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
5 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
100 or 500 mg/kg
Basis:

No. of animals per sex per dose:
3/sex/group

Control group: 10/sex
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOEL
Effect level:
< 100 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: apathy, prone position, slight to severe atactic gait, flat footed gait, partly stradding

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

100 mg/kg: Apathy, prone position, atactic and flat-footed gait during the treatment period (day 1-5)

and slightly extended abdomen within the reversibility period (day 6-15)- slightly decreased body weight gain in females during the treatment and reversibility period (n.s.)

 

500 mg/kg: All treated animals died intercurrently or were sacrificed moribundly between the first and second days of treatment.

Applicant's summary and conclusion

Conclusions:
No hepatotoxic effects found. High dose of 500 mg/kg is lethal for rats.
Executive summary:

Rats (3/sex/group) received progesterone (100 or 500 mg/kg) via gavage over 5 days once daily. The effects were evaluated using clinical observation and liver enzymes (GOT, GPT, APL). Blood samples were taken on day 6. Thereafter all animals were retained 9 - 11 days without treatment to look for reversibility of effects. Finally all animals were sacrificed and necrospied. Animals receiving high dose (500 mg/kg) died or were sacrificed between first and second day of treatment. Animals of low dose group developed clinical symptoms such as atactic gait and prone position during treatment period. Slightly decreased body weight gain was observed in female rats. Hepatotoxic effects could not be determined.