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A registration of estrone was already submitted earlier and is public available on the ECHA website. Chapter 7, which is still valid from today's perspective, was amended to fulfill the current information requirements. Consequently the migrated data (IUCLID 5 to IUCLID 6) was kept unchanged and only modified if there was a need for further information and/or to pass the technical completeness check (TCC).

Estrone is an endogenous sex hormone and an approved drug since several decades. The active ingredient, synthetic estrone, is similar both chemically and biologically to endogenously produced human estrone. Estrone belongs to the category “steroidal estrogens” and is one of the pharmacologically less-active metabolites of 17β-estradiol which is the most potent of the naturally occurring estrogens (17ß-estradiol, estrone, estriol).

The clinical pharmacology and the absorption, distribution, metabolism and excretion of 17ß- estradiol are well characterized as described in the literature* and the current label of approved drugs.

* Kuhnz W, Blode H, Zimmermann H. Pharmacokinetics of exogenous natural and synthetic estrogens and antiestrogens. In: . Oettel M, Schillinger E, eds. Handbook of Experimental Pharmacology, Estrogens and Antiestrogens II. Berlin: Springer Verlag, 1999:261-322

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Additional information

A registration of estrone was already submitted earlier and is public available on the ECHA website. Chapter 7, which is still valid from today's perspective, was amended to fulfill the current information requirements. Consequently the migrated data (IUCLID 5 to IUCLID 6) was kept unchanged and only modified if there was a need for further information and/or to pass the technical completeness check (TCC).

There are no experimental data on ZK 5019 available. All data on ADME are cited in RTECS/HSDB database (Jan 2010): Adsorption/Distribution/Excretion Estrogens are available for oral, parenteral, transdermal, or topical administration ... absorption is generally good with the appropriate preparation. [1] Urinary excretion rate of estrogens is quite similar whether agents are given orally or iv, whch suggests that absorption ... from GI tract is prompt and quite complete [2] Limited oral effectiveness of natural estrogens and their esters is... due to hepatic metabolism. Estrogens... when dissolved in oil and injected, ... are rapidly absorbed and quickly metabolized [3] Estrogens and their esters are handled in body in much the same way as the endogenous hormons. Inactivation of estrogen is carried out mainly in liver. Certain proportion... is excreted into bile, and reabsorbed from intestine [3] Natural estrogens circulate in blood in assoc. with proteins, incl sex hormone-binding globulin and albumin. A significant proportion ...is in form of conjugate, particularly sulfate, which are excreted by the kidney [3] Distribution: To most tissues, especially breast, uterine, vaginal, hypothalamic, and pituitary tissues; high affinity for adipose tissue. [4] Protein binding: Moderate to high (50 to 80% to albumin and sex hormone binding globulin) [4] Elimination: Primarily renal excretion of metabolites, some fecal; undergo extensive enterohepatic recirculation. Prolonged in obese patients.[4] Estrogens are excreted in milk. Potential for decreased milk volume and decreased nitrogen and protein content [5] Metabolism Two new metabolites, isomeric 2,16 alpha-dihydroxyestrone methyl ether ... of estrone have been idetified in bile of treated rats [6] Yields estrone-3 -beta-D-glucuronide in man; estrone-3 -sulfate in man [7] Yields 16 beta-hydroxyestrone probably in man, 17 alpha-estradiol and 17 beta-estradiol in rats; Estrone-3 -beta-D-Galactiside and estrone-3 -beta D glucoside in rabbit [7] Yields 16 -epistriol and 2 -hydroxyestrone in man [7] Yields 1 -(S-glutationly)-2 -hydroxyestrone and 4 -(s-gluta thionyl)-2 -hydroxyestrone probably in rats; 16 alpha-hydroxyestrone in man [7] In dogs, major metabolite of estrone in plasma was its glucoronide, accompanied by small AMT of estradiol-17 beta 3 -glucuronide, estrone sulfate, and estradiol-17 beta 17- glucuronide [8] After ip injection of estrone into female Wistar rats, 2 -hydroxyestrone dlucuronide was major urinary metabolite. [8] Estrone is a metabolite of 17-beta-estradiol, possessing considerably less biological activity. [9] Biotransformation: Primarily hepatic; some metabolism also occurs in muscle, kidneys, and gonads. The metabolic sites for all synthetic estrogens have not been completely determined, although some seem to undergo hepatic change. [4] Estrone ... undergoes conversion and reduction to estriol, which is the major urinary metabolite. [1] Estrone was converted substantially to estradiol (67%), while on 23% was collected as the parent compound. [10] The 17beta-hydroxy steroid dehydrogenase transforms estrone to estradiol reversibly. This enzyme occurred in all tissues of all species examined and is linked to either the cytosolic or microsomal subcellular compartment. In human liver, a NAD-linked 17beta-hydroxy steroid 3-hydrogenase occurs in cytosol and in microsomes, and a further NADP-linked enzyme has been found in cytosol. Hence, estrone and estradiol are largely biologically equivalent; they are also metabolized via the same pathways. [11] Using HPLC and paper chromatography, under the experimental conditions used it was found that liver homogenates from female rats were able to convert estrone to various metabolites such as 16 alpha-hydroxyestrone. [12] [1] Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed.New York, NY: McGraw-Hill, 1996 [2]  Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics.5th ed. New York: Macmillan Publishing Co., Inc., 1975., [3] Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics.8th ed. New York, NY. Pergamon Press, 1990., [4] USP. Convention. USPDI - Drug Information for the Health Care Professional. 19th ed. Volume I.Micromedex, Inc. Englewood, CO., 1999. Content Prepared by the U.S. Pharmacopieal Convention, Inc., [5] Young, L.Y., M.A. Koda-Kimble (eds.). Applied Therapeutics. The Clinical Use of Drugs.6th ed. Vancouver, WA., Applied Therapeutics, Inc. 1995., [6] The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3.London: The Chemical Society, 1975., p. 281 [7] Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds.New York: Wiley, 1976., p. 0-6 [8] The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971.London: The Chemical Society, 1972., [9] Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals.Rahway, NJ: Merck and Co., Inc., 1989 [10] Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons.5th ed. New York, NY: McGraw-Hill, 1995., p. 532 [11] IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT.(Multivolume work)., p. V21 356 (1979) [12] Arts CJ et al; J Steroid Biochem 36 (6): 527-31 (1990)