Androst-4-ene-3,17-dione

Endpoint summary

Description of key information

Oral (Rat-Wistar, males, GLP, similar to OECD TG423): LD50 between 500 and 1000 mg/kg (Schöbel and Flowers, 1989)
Oral (Rat-Wistar, females, GLP, similar to OECD TG423): LD50 > 500 mg/kg (Treher, 1994)
Dermal (Rat-Wistar, GLP, similar to OECD TG402, combined study on acute toxicity and on local tolerance): LD50 > 2000 mg/kg (Kurth, 1995)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04. to 17. July 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

, doses were 1000 and 500 mg/kg

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Wistar-Han-Schering
- Source: Schering
- Age at study initiation: not reported
- Weight at study initiation: 105-123 g
- Fasting period before study: about 19 h
- Housing: singly in conventional housing conditions
- Diet and water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 48-60
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Route of administration:

oral: gavage

Vehicle:

other: physiological saline containing 0.085 % Myrj 53

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 mg/ml

Doses:

500 and 1000 mg/kg bw

No. of animals per sex per dose:

3 males/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs thrice on day 1 (30 min., 1 h, and 2 h after substance sdministration), twice on day 2 (in the morning and in the afternoon), and at least once daily throughout the rest of the study. Body weights were determined at study start (day 1), on day 7 and at termination of the study (day 14).
- Necropsy of survivors performed: yes

Sex:

male

Dose descriptor:

LD50

Effect level:

> 500 - < 1 000 mg/kg bw

Based on:

test mat.

Mortality:

All three animals of dose group 1000 mg/kg died on day 3 of the study. No mortalities were observed after administration of 500 mg/kg.

Clinical signs:

other: Compound-related clinical signs were apathy, disturbance of gait and squatting position. In addition prone position, unconsciousness, disturbance in respiration and increased diuresis were observed at lethal dose (1000 mg/kg). The surviving animals were w

Gross pathology:

Macroscopic findings in animals which died before the end of the observation period were paleness of liver and kidneys and black-brown foci in glandular mucosa of stomach. Animals at the dose of 500 mg/kg were without macroscopic pathological findings.

Conclusions:

The single oral administration of the substance to male rats caused mortality at 1000 mg/kg in 3/3 animals on Day 3 of the study, whereas all three animals survived at 500 mg/kg. Compound-related clinical signs were apathy, disturbance of gait and squatting position and, additionally at lethal dose, prone position, unconsciousness, disturbance in respiration and increased diuresis. All surviving animals were without clinical signs from Day 2 up to the end of the 14 -day observation period. Macroscopic findings in animals which died prematurely were paleness of liver and kidneys and black-brown foci in glandular mucosa of stomach. Animals at the dose of 500 mg/kg were without macroscopic pathological findings. Thus, the LD50 after oral administration to male rats was concluded to be between 500 and 1000 mg/kg bw

Executive summary:

In an acute oral toxicity study similar to OECD TG 423, fasted Wistar rats (3 males/dose) were given a single oral dose by gavage of Androstendione in physiological saline with 0.085% (w/v) Myrj 53 at doses of 500 and 1000 mg/kg bw and observed for 14 days.

Mortality was observed at 1000 mg/kg bw in 3/3 animals on Day 3 of the study, whereas all three animals survived at 500 mg/kg bw. Compound-related clinical signs were apathy, disturbance of gait and squatting position and, additionally at lethal dose, prone position, unconsciousness, disturbance in respiration and increased diuresis. All surviving animals were without clinical signs from Day 2 up to the end of the 14 -day observation period. Macroscopic findings in animals which died prematurely were paleness of liver and kidneys and black-brown foci in glandular mucosa of stomach. Animals at the dose of 500 mg/kg were without macroscopic pathological findings. Thus, the LD50 after oral administration to male rats was concluded to be between 500 and 1000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 500 - < 1 000 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

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23. Feb to 22. March 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Amendment to Annex VI of the Directive 67/548 EEC in the version of EEC Directive 93/21 EEC and "Gefahrstoffverordnung, Stand Oct. 94"

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

3 rats/sex and dose group

Principles of method if other than guideline:

According to Schlede et.al., A national validation study of the acute-toxic-class method - an alternative to the LD50 test, Arch. Toxicol. 66, 7, 1992, 455-470.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: HAN: WIST (SPF)
- Source: Schering AG
- Age at study initiation: not reported
- Weight at study initiation: males 106-112 g, females 101-111 g
- Fasting period before study: about 18.5 h
- Housing: singly in conventional housing conditions
- Diet and water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 54-62
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

other: 0.9 % saline solution

Details on dermal exposure:

212-224 mg/male rat; 208-222 mg/female rat
The test substance was formulated with 0.9 mL physiological saline solution and then applied as a paste onto the skin.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs several times on day 1 and at least once daily throughout the rest of the study. Body weights were determined at study start (day 1), on day 7 and at termination of the study (day 14).
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No animal died in the course of the study.

Clinical signs:

other: No compound-related clinical signs were observed.

Gross pathology:

Autopsy revealed no compound-related findings.

Conclusions:

The single dermal administration of 2000 mg/kg to male and female rats was tolerated without compound-related clinical signs or effects on body weights during the 14 -day observation period. At necropsy no compound-related findings were detected. Thus, the LD50 for acute dermal toxicity was concluded to be above 2000 mg/kg bw.

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) (3/sex) were dermally exposed to Androstendione in physiological saline for 24 hours at a limit dose of 2000 mg/kg bw under semiocclusive conditions.  Animals then were observed for 14 days.

The administration of the test substance was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings.

The dermal LD50 of the test substance is therefore > 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

Acute oral toxicity

In an acute oral toxicity study similar to OECD TG 423, fasted Wistar rats (3 males/dose) were given a single oral dose by gavage of Androstendione in physiological saline with 0.085% (w/v) Myrj 53 at doses of 500 and 1000 mg/kg bw and observed for 14 days.

Mortality was observed at 1000 mg/kg bw in 3/3 animals on Day 3 of the study, whereas all three animals survived at 500 mg/kg bw. Compound-related clinical signs were apathy, disturbance of gait and squatting position and, additionally at lethal dose, prone position, unconsciousness, disturbance in respiration and increased diuresis. All surviving animals were without clinical signs from Day 2 up to the end of the 14 -day observation period. Macroscopic findings in animals which died prematurely were paleness of liver and kidneys and black-brown foci in glandular mucosa of stomach. Animals at the dose of 500 mg/kg were without macroscopic pathological findings. Thus, the LD50 after oral administration to male rats was concluded to be between 500 and 1000 mg/kg bw (Schöbel and Flowers, 1989).

 

In an acute oral toxicity study similar to OECD TG 423, fasted Wistar rats (3 females/dose) were given a single oral dose by gavage of Androstendione in physiological saline with 0.085% (w/v) Myrj 53 at doses of 250 and 500 mg/kg bw and observed for 14 days.

The administration of the substance caused transient compound-related clinical signs at 250 and 500 mg/kg bw (apathy and atactic gait). All animals were without compound-related findings from Day 2 onwards. No compound-related or suspected compound-related macroscopic findings were seen at necropsy. Thus, the LD50 after oral administration to female rats was concluded to be above 500 mg/kg bw (Treher, 1994).

 

 

Acute dermal toxicity

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) (3/sex) were dermally exposed to Androstendione in physiological saline for 24 hours at a limit dose of 2000 mg/kg bw under semiocclusive conditions.  Animals then were observed for 14 days.

The administration of the test substance was tolerated without mortalities, compound-related clinical findings, effects on body weight gain and gross pathological findings.

The dermal LD50 of the test substance is therefore > 2000 mg/kg body weight (Kurth, 1995).

 

Further study results with androstendione are cited in RTECS database (April 2013):

 

The single intraperitoneal application to rats resulted in behavioral effects (- general anaesthetic, - alteration of classical conditioning; TDLo: 340 mg/kg [Clinical Pharmacology and Therapeutics. (American Society for Clinical Pharmacology and Therapeutics, St. Louis Mo Mosby-Year Book) V.1- 1960- v. 14, p. 727, 1976 (CLPTAT)].

Justification for classification or non-classification

For acute oral toxicity classification required as Acute Tox. 4 (H302: harmful if swallowed) according to Regulation (EC) 1272/2008.

 

No classification required for acute dermal or inhalation toxicity according to Regulation (EC) 1272/2008.