Androstan-17-one, 2,3-epoxy-16-(1-pyrrolidinyl)-, (2.alpha.,3.alpha.,5.alpha.,16.beta.)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 October 1997 - 13 November 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted according to international guideline and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

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:

928-664-5

EC Number:

928-664-5

IUPAC Name:

928-664-5

Constituent 2

Reference substance name:

(1S,2S,4R,6S,8S,11R,12S,14S,16S)-2,16-dimethyl-14-(pyrrolidin-1-yl)-5-oxapentacyclo[9.7.0.0²,⁸.0⁴,⁶.0¹²,¹⁶]octadecan-15-one

Cas Number:

159325-45-8

Molecular formula:

C23H35NO2

IUPAC Name:

(1S,2S,4R,6S,8S,11R,12S,14S,16S)-2,16-dimethyl-14-(pyrrolidin-1-yl)-5-oxapentacyclo[9.7.0.0²,⁸.0⁴,⁶.0¹²,¹⁶]octadecan-15-one

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Epyrron
- Physical state: Off white powder
- Composition of test material, percentage of components: Main Component 55%
Other: 22% & 18%
- Lot/batch No.: GV-1458 K1
- Expiration date of the lot/batch: 24 September 1998
- 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 River, Sulzfeld, Germany
- Age at study initiation: 9 weeks
- Housing: Group housing (polycarbonate cages) 3 animals per sex
- Diet (e.g. ad libitum): Free access, standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhour, Belgium).
- Water (e.g. ad libitum): Free access to tap-water
- Acclimation period: At least 5 days

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

IN-LIFE DATES: From: 28 October 1997 To: 13 November 1997

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

Doses:

2000 mg/kg (10 ml/kg) body weight

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 Weight - Days 1 (pre-administration), 8 and 15; Clinical Signs - periodic intervals on day of dosing, and once daily thereafter, until day 15.
- Necropsy of survivors performed: Yes
- Other examinations performed: Necropsy was performed at the end of the observation period and internal macroscopic abnormalities were recorded.

Statistics:

None performed

Results and discussion

Preliminary study:

Since the 2000 mg/kg limit test resulted in no adverse effects, or mortalities in the 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 occurred.

Clinical signs:

other: There were no signs toxicity throughout the 15 day observation period. All male and females animals appeared normal throughout the observation period.

Gross pathology:

No abnormalities were observed at the macroscopic level for all animals necropsied at the conclusion of the 15-day observation period.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance, when administered as supplied to 3 male and 3 female Wistar rats, indicates an acute oral LD50 greater than 2000 mg/kg.

Executive summary:

The oral LD50 value of the test substance in Wistar rats was established as greater than 2000 mg/kg body weight.