9beta,11beta-Epoxy-6alpha-fluoro-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb to Apr 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: EEC Commission Directive no. 79/831 EEC of.18. September 1979 (equivalent to the corresponding German regulations)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

study was conducted prior to implementation of OECD TG 423

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

9beta, 11beta-Epoxy-6alpha-fluoro-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione

Cas Number:

65535-29-7

Molecular formula:

C27 H35 F O5

IUPAC Name:

9beta, 11beta-Epoxy-6alpha-fluoro-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: males: 102-115 g; females: 89-91 g
- Fasting period before study: Males ca. 20.25 h, females ca. 18.5 h
- Housing: individually under conventional conditions
- Diet (e.g. ad libitum): pell. Altromin R ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 50-76

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidest water

Doses:

2000 mg/kg

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 at 30 min, 1 h, and 3 h after dosing, day 2-14. Body weight at day 1, 7, 8 and 14
- Necropsy of survivors performed: yes
- Clinical signs including body weight: apathy, slight; diarrhea, slight

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 study.

Clinical signs:

other: The administration of 2000 mg/kg bw provoked slight apathy in two females as well as slight diarrhea in one female on application day 1. All animals were without any clinical findings from day 2 onwards.

Gross pathology:

Necropsy revealed no compound-related findings after 2000 mg/kg bw.

Applicant's summary and conclusion

Conclusions:

A single oral administration (gavage) of the test substance to male and female rats at the limit-dose 2000 mg/kg bw was tolerated without mortalities, effects on body weight gain and gross pathological findings. Slight apathy in two females as well as slight sialorrhea in one female was seen on application day 1. All animals were without any clinical findings from day 2 onwards. According to OECD TG 423 the oral LD50 of ZK 50992 (epoxide valerate) in male and female rats is therefore > 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study conducted equivalent to OECD TG 423, groups Wistar rats, female and male (3/sex) were given a single oral dose of Epoxide-Valerate in 0.9 % NaCl + 0.085 % Myrj 53 in bidist. water at a dose of 2000 mg/kg bw and observed for 14 days.

 

Oral LD50 Combined => 2000 mg/kg bw

 

Limit test

No mortality occurred during the test

The administration of 2000 mg/kg bw provoked slight apathy in two females as well as slight diarrhea in one female on application day 1. All animals were without any clinical findings from day 2 onwards. There were no necropsy findings or changes in body weight.

The test item is of low Toxicity based on the LD50 in male and female Wistar rats.