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EC number: 612-953-5 | CAS number: 6218-29-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
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
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