Estr-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:

July to Aug 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Estr-4-ene-3,17-dione

EC Number:

211-995-8

EC Name:

Estr-4-ene-3,17-dione

Cas Number:

734-32-7

Molecular formula:

C18H24O2

IUPAC Name:

estr-4-ene-3,17-dione

Test material form:

other: solid

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.