Progesterone

Endpoint summary

Description of key information

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.

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.