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A study in Spraque-Dawley Rats with daily intragastrically  application over a period of 5 days revealed apathy and slightly decreased body weight gain during the treatment and reversibility period. Female rhesus monkeys had acyclic menses, lack of vaginal cornification, increase of parenchymal breast cells and lacktic efflux after treatment with 5.0 and 50.0 mg/kg Progesterone. Further data from animal studies implicate an effect on tumorigenesis in female reproductive organs.
The endogenous production of progesterone during pregnancy amounts to an estimated 200 mg per day and orally administered progesterone is inactivated very rapidly in the liver so no organ toxic effects have to be reckoned with after repeated oral exposure to dose levels of this order of magnitude. However, known side effects of progestogens in humans such as headache, gastro-intestinal disturbances, weight increase and impairment of liver function have also to be reckoned after repeated exposure to progesterone. The therapeutic dose level for parenteral administration begins with appr. 5 to 10 mg/person/day.

Key value for chemical safety assessment

Additional information

Animal Data

Test system

Substance

Application

Test concentration

End Point/Effect

Literature

Rat

 

Intraperitoneal

750 mg/kg/15 d
 
TDLo Endocrine (change in LH); blood (changes in serum composition);
related to chronic data (changes in
prostate weight).
Toxicological
Sciences University Press,
6277
Drive,,
FL 32887) V. 41,
Jan. 1998-, vol
54, pg 338, 2000.
Spraque-
Dawley
Rat, juvenile

3 male

and 3

female

 

Progesterone

daily

intragastrically

application

over a period

of 5 days with

Microcrystalline

 suspensions.

 

100 or 500
mg/kg

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.

Schering Research Report No. AN56, Testosterone,

Progesterone, Norethisterone

acetate, spironolactone,

gestodene Systemic tolerance study with special regard to

liver toxicity in juvenile

Spraque-Dawley rats

after daily per os (intragastric)

administration over 5 days, dated 08. Jul. 1999.

Female Dog

 

Longterm

subcutaneous

injections

 

Endometrial hyperplasia,

inhibition of ovarian

development, marked mammary hyperplasia, and

some fibroadenomatous nodules of the mammary gland.

IARC. 1979. Sex Hormones (II). IARC Monographs on the Evaluation of Carcinogenic

Risk of Chemicals to Humans, vol. 21. Lyon,:

International Agency for Research on Cancer;

IARC. 1982. Chemicals,

Industrial Processes and Industries Associated with

Cancer in Humans. IARC

Monographs on the Evaluation of Carcinogenic

Risk of Chemicals to Humans,

Supplement 4. Lyon,: International Agency for

Research on Cancer. 292 pp

Rhesus
monkey. 4
Female
per group

Progesterone

subcutaneous injection

0.5, 5.0 and
50.0 mg/kg

Acyclic menses in all doses, lack of vaginal cornification, increase of parenchymal breast cells and lacktic efflux at 5.0 and 50.0 mg/kg. Increased insulin level.

Decrease in adrenal gland

weight.

Schering Report

No. 3796, Limitierte

systemische

Verträglichkeitsprüfung

von ZK 9471, ZK

5931, ZK 18206 und

ZK 4981 an Rhesusaffen bei 12- wöchiger Verabreichung, dated 04 April 1979.

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC and Regulation (EC) 1272/2008 (CLP) is not required.