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Diss Factsheets

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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
not specified
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

Constituent 1
Chemical structure
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:
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.
Body weight:
The mean body weight gained was within the range expected for rats used in this type of study and was therefore not considered related to toxicity.
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.