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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 - 25 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 402 (Acute Dermal Toxicity)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute 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: >/= 95%
- Lot/batch No.:DGN105K1A
- Expiration date of the lot/batch: 01 January 2001
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature in dark.
- Other:

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks old
- Weight at study initiation: <3.5 kg
- Fasting period before study: none
- Housing: Individually housed in polycarbonate cages
- Diet (e.g. ad libitum): free access to standard pelleted laboratory animal diet (from Carfil Quality BVBA, Oud-Turnhout, Belgium)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: none

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 degrees C
- Humidity (%): 50%
- Air changes (per hr): 15 air changes per hr
- Photoperiod (hrs dark / hrs light): Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

IN-LIFE DATES: From: To: 17 August 1999 to 20 August 1999

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- % coverage: 10% total body surface
- Type of wrap if used: Wrap consisted of surgical gauze patch, successively covered with aluminium foil and Coban flexible bandage. Micropore tape was used in females for fixation of bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): No data
- Constant volume or concentration used: Yes
- For solids, paste formed: No data

Duration of exposure:

24 hrs

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not specified

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 - At periodic intervals on the day of dosing 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:

The test substance, when administered as supplied to rats, indicated an acute dermal LD50 greater than 2000 mg/kg.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Mortality:

No mortality occurred

Clinical signs:

other: No signs of systemic toxicity were reported. Alopecia, focal erythema, necrosis and/or scabs were seen in the treated skin-area of the animals during the observation period.

Gross pathology:

Macroscopic findings were only noted in two males; for one male liver nodules and a hernia of the diaphragm were reported and for the other male a thickened enlarged liver was reported.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test substance, when administered as supplied to rats, was greater than 2000 mg/kg.