Androst-4-ene-3,17-dione

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

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

Test guideline 2

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

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/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

Administration / exposure

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

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.