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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No internal reproduction toxicity studies of Hydroxyestradienon are available. 
However results of in vitro receptor binding studies are published (Feb 2012):
Relative binding affinitiy for cytosol estrogen receptor of mouse uterus: no affinity
Relative binding affinitiy for cytosol androgen receptor of rat prostate: high affinity
Relative binding affinitiy for cytosol progestin receptor of estrogen-primed immature rabbit uterus: partial affinity
Relative binding affinitiy for cytosol mineralocorticoid receptor of rat kidney: no affinity
Relative binding affinitiy for cytosol glucocorticoid receptor of rat liver: low affinity
(Ojasoo, T. and Raynaud, J.-P. 1978, Cancer Research, V. 38, pp. 4186-4198)
(Ojasoo, T. et al. 1987, J. steroid Biochem., Vol. 27, No. 1-3, pp. 255-269)
Additional information

Due to the high affinity of Hydroxyestradienon to androgen and partial affinity to progesteron receptors an effect on fertility/reproduction can be expected.


Short description of key information:
No internal reproduction toxicity studies of Hydroxyestradienon are available.
However, results of in vitro progesterone and androgen receptor binding studies are published (Feb 2012): see below: developmental toxicity and other studies

Effects on developmental toxicity

Description of key information
No internal developmental toxicity studies of Hydroxyestradienon are available. 
However, results of a study to examine in vitro progesterone binding and biological activity are published (Feb 2012):
Relative binding affinitiy for cytosol progesterone receptor of estrogen-primed immature rabbit uterus: partial affinity
in vivo biological tests for progestational, antiprogestational and abortifacient activities: mixed agonist/antagonist on progesterone receptor; embryolethal and abortifacient activity in rats
(Reel, J.R. et al. 1979, Fertility and Sterility, Vol. 31, No. 5, pp. 552-561)
Additional information

Hydroxyestradienon as well as the structurally very similar 19 -Nortestosterone were shown to bind partially to the progesterone receptor (Relative Binding Activity (RBA) of Hydroxyestradienon = 26).

To assess the progestational and antiprogestational activity of Hydroxyestradienon and 19 -Nortestosterone the substances were administered subcutaneously to estrogen-primed immature rabbits for 4 consecutive days at doses of 20 mg/day (both substances progestational activity and Hydroxyestradienon also antigestational activity) or 5, 10 and 20 mg/day (19 -Nortestosterone antigestational activity). The endometrial gland proliferation was measured and scored from 0 to 4 (maximal proliferation) according to the grading system of McPhail. Hydroxyestradienon as well as 19 -Nortestosterone showed to be active progestagens as well as active antagonists.

Moreover, pregnant rats received daily subcutaneous injections from day 7 through day 12 of pregnancy to examine the postnidatory termination of pregnancy. 19 -Nortestosterone and Hydroxyestradienon effectively interrupted normal pregnancy in 50% (ED50) of the rats at daily doses of 3 or 5 mg, respectively.

In summary, Hydroxyestradien as well as 19 -Nortestosterone bound partially to the progesterone receptor in vitro and possessed in vivo both progestational and antiprogestational activity and therefore, behaved as partial agonists/antagonists. Moreover, Hydroxyestradienon and 19 -Nortestosterone terminated pregnancy in the rat

Toxicity to reproduction: other studies

Additional information

The relative bindings affinities (RBAs) of different steroid ligands (amongst others Hydroxyestradienon and 19 -Nortestosterone) for the cytosol estrogen receptor of mouse uterus, the cytosol androgen receptor of rat prostate, the cytosol progestin receptor of estrogen-primed immature rabbit uterus and the cytosol mineralocorticoid and glucocorticoid receptor of rat kidney or liver, respectively, were measured in a routine screening system after incubation for 2 h at 0°C. Hydroxyestradienon was shown to have no affinity to the estrogen and the mineralocorticoid receptor but a high affinity to the androgen receptor, a partial affinity to the progestin receptor and a low affinity to the glucocorticoid receptor. The RBAs for Hydroxyestradienon were comparable to that of the structurally very similar 19 -Nortestosterone (CAS 434 -22 -0), a known anabolic steroid as can be seen from the following table:

RBAs measured on cytosol receptors (see above) after incubation for 2 h at 0°C. The RBAs of estradiol, testosterone, progesterone, aldosterone and dexamethasone were set at 100

   Estrogen receptor  Androgen receptor  Progestin receptor  Mineralocorticoid receptor  Glucocorticoid receptor
 19 - Nortestosterone  0  154  20 1 -3   0
 Hydroxyestradienon  0  134 17   0  1 -3

Justification for classification or non-classification

Due to the pharmacological effect of Hydroxyestradienon (binds with high affinity to androgen and partial affinity to progesteron receptors (with mixed progesterone receptor agonist/antagonist activity)) which is comparable to that of the structurally very similar 19 -Nortestosterone (a known anabolic steroid) and due to the findings in the animal study (embryolethal and abortifacient action) a classification with T, Repr. Cat 1, R60 and Repr. Cat. 2, R61 according to Directive 67/548/EEC and with Repr. 1A, H360 FD according to Regulation (EC) No. 1272/2008 (CLP) is required.

Additional information