Hydroxyprogesterone

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Amendment to Annex VI of the Oirective 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 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:

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: 112-120 g; females: 101-107 g
- Fasting period before study: ca. 16.5-19 h
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-24°C
- Humidity (%): 58-62%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: males: 30. Aug - 12. Sep 1995; females 6. - 19. Sep 1995

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: 0.9% (w/v) NaCl-solution

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied: males 224-240 mg; females 202 - 214 mg
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied: males 0.4 ml; females 0.3 ml

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

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 during the study.

Clinical signs:

other: The test item was tolerated without compound-related findings.

Gross pathology:

Autopsy revealed no compound-related findings.

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. 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 HAN: WIST rats (3/sex) (3/sex) were dermally exposed to hydroxyprogesterone acetate 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.