Estr-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:

Aug to Sep 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Cross-reference

Reason / purpose for cross-reference:

reference to same 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 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

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: 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

Administration / exposure

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

Results and discussion

Effect levels

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

Any other information on results incl. tables

 

Applicant's summary and conclusion

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.