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EC number: 211-995-8 | CAS number: 734-32-7
- 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
Description of key information
The acute toxicity (LD50) of norandrostendion in rats is > 1000 < 2000 mg/kg bw after oral administration (Kurth, 1996) or > 2000 mg/kg bw after dermal administration (Kurth, 1996).
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- July to Aug 1995
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- 1996
- Deviations:
- yes
- Remarks:
- In contrast to annex 3c of OECD TG 423 in its version of 1996 the starting dose (2000 mg/kg) was not applied to the second sex (females) although only 1/3 males died after application of 2000 mg/kg.
- GLP compliance:
- not specified
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: HAN: WIST (SPF)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: males: 98-118 g, females: 89-95 g
- Fasting period before study: ca. 19-21 hours
- Housing: 1 animal/cage
- Diet (e.g. ad libitum): pell. Altromin® R, ad libitum 24 hours per day
- Water (e.g. ad libitum): demineralized acidified water, pH 2-3, ad libitum
- Acclimation period: 7 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-24°C
- Humidity (%): 42-60%
- Photoperiod (hrs dark / hrs light): 12/12
- Route of administration:
- oral: gavage
- Vehicle:
- other: physiological saline with 0.085% (w/v) Myrj 53
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 20 and 200 mg/mi - Doses:
- 200 mg/kg (both sexes), 2000 mg/kg (only males)
- No. of animals per sex per dose:
- 3
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of weighing: start (day 1), on day 8 and at the end (day 14) of the study
- Necropsy of survivors performed: yes
- Clinical signs including body weight - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 1 000 - < 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- One animal died after application of 2000 mg/kg on day 1 (3.5 hours post application) of the test.
- Clinical signs:
- other:
- Body weight:
- other body weight observations
- Remarks:
- within normal range for rats (M+F) of the age and strain
- Gross pathology:
- Autopsy revealed no compound-related findings.
- Conclusions:
- A single oral administration of the test substance by gavage to male rats at the limit-dose 2000 mg/kg was lethal for 1/3 animals. 200 mg/kg were tolerated without mortalities, clinical effects, effects on body weight gain and gross pathological findings in both sexes. According to OECD TG 423 the oral LD50 of the test substance is therefore: 1000 < LD50 < 2000 mg/kg body weight.
- Executive summary:
In an acute oral toxicity study similar to OECD TG 423, fasted Wistar rats were given a single oral dose by gavage of Norandrostendione in physiological saline with 0.085% (w/v) Myrj 53 at doses of 200 mg/kg (both sexes), 2000 mg/kg (only males) and observed for 14 days.
The administration of the test item at 2000 mg/kg bw resulted in transient clinical signs (apathy, prone position, unconsciousness, disturbances in gait and in respiration and eyelid closure). The surviving animals of this dose group were without findings from day 1 (4.5 hours after application) onwards. All animals treated with 200 mg/kg were without findings over the whole study period. The body weight gain observed on day 8 and at the end (day 14) of the test was within the normal range tor rats (M+F) of the age and strain. Autopsy revealed no compound-related findings.
The LD50 of the test item in male and female rats after a single oral application is > 1000 mg/kg body weight, probably near 2000 mg/kg.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- > 1 000 - < 2 000 mg/kg bw
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Aug to Sep 1995
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- 1981
- Deviations:
- yes
- Remarks:
- 3 instead of 5 animals/sex used
- GLP compliance:
- yes
- Remarks:
- - but a QA check was not performed
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: HAN: WIST (SPF)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: males: 104-116 g, females: 97 -102 g
- Fasting period before study: ca. 18.5-19.5 hours
- Housing: 1/cage
- Diet (e.g. ad libitum): pell. Altromin® R, ad libitum 24 hours per day
- Water (e.g. ad libitum): demineralized acidified water, pH 2-3, ad libitum
- Acclimation period: 7 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-24°C
- Humidity (%): 58-62%
- Photoperiod (hrs dark / hrs light): 12/12
- Type of coverage:
- occlusive
- Vehicle:
- other: 0.9% (w/v) NaCl-solution
- Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 3
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day 1, 7 and 14
- Necropsy of survivors performed: yes - Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No animal died in the course 'of the test.
- Clinical signs:
- other: A single dermal application of 2000 mg/kg was tolerated without compound-related findings.
- Body weight:
- other body weight observations
- Remarks:
- The body weight gain on days 7 and 14 was within the normal range for rats of this age and strain, which are routinely used in the laboratory.
- Gross pathology:
- No compound- related clinical findings could be detected at the end of the study on day 14. Autopsy revealed no compound-related findings.
- Other findings:
- the administration was tolerated without any local irritations
- Conclusions:
- A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings. According to OECD TG 402 the dermal LD50 of the test substance is therefore > 2000 mg/kg body weight.
- Executive summary:
In an acute dermal toxicity study similar to OECD TG 402 performed as a combined study on acute toxicity and on local tolerance Wistar rats (3/sex) were dermally exposed to Norandrostendione in physiological saline for 24 hours at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.
The administration of the test substance was tolerated without any clinical or macroscopic pathological finding. The dermal LD50 of the test substance is therefore > 2000 mg/kg body weight.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- > 2 000 mg/kg bw
Additional information
For the assessment of acute toxicity, studies on Norandrostenedione are available. Studies on the source substance Norethisterone are included to justify the read-across for higher tier toxicological endpoints.
Oral studies
An acute oral toxicity study in rats was performed according to OECD TG 423 (limit test). A single oral administration of Norandrostenedione by gavage to male rats at the limit-dose 2000 mg/kg was lethal for 1/3 animals, whereas 200 mg/kg were well tolerated. The oral LD50 of the test substance is therefore: 1000 < LD50 < 2000 mg/kg body weight, which leads to a self-classification of acute toxic cat. 4 according to CLP (Kurth, 1996).
In an acute oral toxicity study similar to OECD TG 423, fasted females SD rats were given a single oral dose by gavage of Norandrostendione and observed for 14 days.
300 mg/kg bw was selected as the initial dose. In each group, three female SD rats were exposed to one dose. The first group and the second group were exposed
to 300 mg/kg bw; the third group and the fourth group were exposed to 2000 mg/kg bw.
First group (300 mg/kg bw): observation of moribund state: no animals died in the test period. Clinical observation: no abnormalities were seen in any of the animals. Gross necropsy: no abnormalities were seen in any of the animals. Body weight: in the test period, all animals continued to gain weight after exposure.
Second group (300 mg/kg bw): observation of moribund state: no animals died in the test period. Clinical observation: no abnormalities were seen in any of the animals. Gross necropsy: no abnormalities were seen in any of the animals. Body weight: in the test period, all animals continued to gain weight after exposure.
Third group (2000 mg/kg bw): observation of moribund state: one animal died in the test period. Clinical observation: one animal spontaneously reduced movements and lay on its side; no abnormalities were seen in any of the other animals. Gross necropsy: one animal had changes of a dark red colour in the lungs; no abnormalities were seen in any of the other animals. Body weight: in the test period, all surviving animals continued to gain weight after exposure.
Fourth group (2000 mg/kg bw): observation of moribund state: one animal died in the test period. Clinical observation: one animal spontaneously reduced movements and lay on its side; no abnormalities were seen in any of the other animals. Gross necropsy: one animal had changes of a dark red colour in the lungs; no abnormalities were seen in any of the other animals. Body weight: in the test period, all surviving animals continued to gain weight after exposure.
In this study, the oral LD50 of Norandrostendione in female SD rats was larger than 2000 mg/kg bw (Lei, 2020).
Dermal study
A combined acute dermal toxicity and local tolerance study in rats with 24h semi-occlusive exposure to the skin comparable to TG 402 & 404 was used with Norandrostenedione. This study was conducted as limit test (2000 mg/kg) and showed no compound-related findings. According to OECD TG 402 the dermal LD50 of the test substance is therefore > 2000 mg/kg body weight.
In conclusion, Norandrostenedione is classified for acute oral toxicity Cat. 4. However, the dermal LD50 is above 2000 mg/kg (limit test).
Acute oral toxicity studies for Norethisterone and Norandrostenedione
| Norandrostenedione
|
CAS no. | 734-32-7 |
Study type | Acute oral (key studies) |
Report no./author/year | X050 (Draft), Kurth, 1996 |
GLP/ OECD TG/ deviations | GLP not specified, similar to OECD 423; In contrast to annex 3c of OECD TG 423 in its version of 1996 the starting dose (2000 mg/kg) was not applied to the second sex (females) although only 1/3 males died after application of 2000 mg/kg. |
Species; animals/ group | Rat (Wistar), n= 3 animals/sex/group |
Doses/ route/ schedule | 200 (both sexes) – 2000 mg/kg (only males), p.o., single treatment |
Formulation | Batch No. 21401335, stability unknown Vehicle: physiological saline with 0.085% Myrj 53 |
observation period | 14d |
Results | 1/3 male died after application of 2000 mg/kg on day 1 (3.5 hours post application) main clinical findings after application of 2000 mg/kg were apathy, prone position, unconsciousness, disturbances in gait and in respiration and eyelid closure. The surviving animals of this dose group were without findings from day 1 (4.5 hours after application) onwards 200 mg/kg were tolerated without mortalities, clinical effects, effects on body weight gain and gross pathological findings in both sexes LD50 > 1000 < 2000 mg/kg (male/female) |
Reliability | 2 |
|
|
Report no./author/year | G1901B0160, Lei, 2020 |
GLP/ OECD TG/ deviations | GLP, similar to OECD TG 423; Chinese guideline: Ministry of Environmental Protection of the People’s Republic of China. Guidelines of Chemical Testing (HJ/T 153-2004) Appendix A 423 Acute Oral Toxicity Test: Acute Toxicity Stepwise Method |
Species; animals/ group | Rat (Sprague-Dawley), n= 6 females/group |
Doses/ route/ schedule | First group: 300 mg/kg b.w.; Second group: 300 mg/kg b.w.; Third group: 2000 mg/kg b.w.; Fourth group: 2000 mg/kg b.w. p.o., single treatment |
Formulation | Batch no.: 39541905010 Concentration in vehicle (water): 30, 200 mg/mL Dose volume: 10 mL/kg b.w. |
observation period | 14 d |
Results | 300 mg/kg bw: no mortality in the test period; 2000 mg/kg bw: 2/6 animals died; these animals showed spontaneously reduced movements and lay on its side; dark red colour in the lungs; no abnormalities were seen in any of the other animals
LD50(female)>2000 mg/kg bw |
Reliability | 1 |
Justification for classification or non-classification
With regard to acute oral toxicity the following self classification for norandrostendion is recommended according to Regulation (EC) No. 1272/2008 (CLP) :
Acute Tox. 4 (H302: Harmful if swallowed).
No classification is required for acute dermal toxicity according to Regulation (EC) No. 1272/2008 (CLP).
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