Androst-4-ene-3,17-dione

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Androst-4-ene-3,17-dione

EC Number:

200-554-5

EC Name:

Androst-4-ene-3,17-dione

Cas Number:

63-05-8

Molecular formula:

C19H26O2

IUPAC Name:

androst-4-ene-3,17-dione

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.