Androstane-3,17-diol, 2-(4-morpholinyl)-16-(1-pyrrolidinyl)-, 17-acetate, (2.beta.,3.alpha.,5.alpha.,16.beta.,17.beta.)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 July 1999 - 5 August 1999

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

not specified

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Androstan-3,17-diol,2-(4-morpholinyl)-16-(1-pyrrolidinyl)-, 17-acetate (2α,3α,5α,16α,17β)-

EC Number:

601-596-0

Cas Number:

119302-24-8

Molecular formula:

C29H48N2O4

IUPAC Name:

Androstan-3,17-diol,2-(4-morpholinyl)-16-(1-pyrrolidinyl)-, 17-acetate (2α,3α,5α,16α,17β)-

Test material form:

other: Solid

Details on test material:

- Name of test material (as cited in study report): Pymorolac
- Physical state: Cream white solid
- Analytical purity: Greater than 95%
- Lot/batch No.: DGN105K1A
- Expiration date of the lot/batch: 01 January 2001
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Rive Deutschland, Sulzfeld, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: Male mean: 292 grams; Female mean 203 grams
- Fasting period before study: overnight before dosing and 3-4 hours after dosing.
- Housing: Group housing of 3 animals per sex in polycarbonate cages.
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhout, Belgium).
- Water (e.g. ad libitum): Free access to tap-water
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 July 1999 To: 5 August 1999

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Vehicle was selected based on a pretest performed at NOTOX.


MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg (10 mL/kg) body weight

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: 15 days
- Frequency of observations and weighing: Mortality/Viability - Twice daily; Body weights - Days 1 (pre-administration), day 8, and day 15; Clinical signs - periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Internal macroscopic abnormalities

Statistics:

Not applicable

Results and discussion

Preliminary study:

As the 2000 mg/kg limit test resulted in no adverse effects, or mortalities in this study group, no additional dose levels were required.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was reported within this study.

Clinical signs:

other: Diarrhea, red staining of the eye, hunched posture and/or piloerection were noted among the animals between day 2 and 4. Alopecia, was noted during the observation period, and is commonly seen in group housed rats and therefore was not counted as toxicolo

Gross pathology:

Macroscopic examination of animals reported irregular surface of the fore-stomach in three males and one female. In one female the serosa and the liver were reported to be grown together. In one male the serosa was reported to be grown together with the diaphram and liver.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 for the test substance, when administered as supplied to rats, is >2000 mg/kg.