Hydroxyprogesterone

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

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"

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

Deviations:

yes

Remarks:

The application of 2000 mg/kg to three animals was repeated with three animals of a different sex.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxyprogesterone acetate

EC Number:

206-119-6

EC Name:

Hydroxyprogesterone acetate

Cas Number:

302-23-8

Molecular formula:

C23H32O4

IUPAC Name:

3,20-dioxopregn-4-en-17-yl acetate

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
- Age at study initiation: not specified
- Weight at study initiation: males: 98-113 g; females: 89-106 g
- Fasting period before study: ca. 19-20 h
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-24°C
- Humidity (%): 42-58%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: males: 11. - 24. Jul 1995; females 20. Jul - 02. Aug 1995

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: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Lot/batch no. (if required): males: G/7160-1; females: G/7170



CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit dose

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 + 3 (males + females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: day 8 and 14
- Necropsy of survivors performed: yes

Statistics:

Not applicable.

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 after application of 2000 mg/kg of the test compound during the study.

Clinical signs:

other: The compound was tolerated without clinical signs.

Gross pathology:

Autopsy revealed no compound-related or suspected compound-related findings.

Applicant's summary and conclusion

Conclusions:

A single oral administration of the test substance by gavage to three male and three female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, clinical effects, effects on body weight gain and gross pathological findings in both sexes. The oral LD50 of the test substance is therefore: LD50 > 2000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study similar to OECD TG 423, fasted HAN: WIST rats (3/sex) were given a single oral dose by gavage of hydroxyprogesterone acetate in physiological saline with 0.085% (w/v) Myrj 53 at the limit dose 2000 mg/kg and observed for 14 days.

The administration was tolerated without mortalities, clinical effects, effects on body weight gain and gross pathological findings in both sexes.

The oral LD50 of hydroxyprogesterone acetate is therefore: LD50 > 2000 mg/kg body weight.