Androstan-17-ol, 2,3-epoxy-16-(1-pyrrolidinyl)-, (2.alpha.,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:

30 October 1997 - 13 November 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted according to OECD guideline 402 and EU Method B.3 (Acute Dermal Toxicity Test) without deviations and GLP practices. .

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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

601-593-4

Cas Number:

119302-19-1

Molecular formula:

C23H37NO2

IUPAC Name:

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

Details on test material:

- Name of test material (as cited in study report): Epyrrol
- Substance type: pure active substance
- Physical state: Powder, off white in color
- Composition of test material, percentage of components: Main component= 75%, other= 18%, other= 7%
- Lot/batch No.: GL-1291 K1
- Expiration date of the lot/batch: 24 September 1998
- Stability under test conditions: Not indicated
- Storage condition of test material: Stable 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: 9-10 weeks old
- Weight at study initiation: 298 g (male mean) and 226 g (female mean)
- Fasting period before study: Food was withheld overnight prior to dosing until approximately 3-4 hours after treatment of the test substance
- Housing: Group house of 3 animals per sex per cage in labelled polycarbonatge cages
- Diet (e.g. ad libitum): Standard pelleted laboratory diet (from Carfil Quality BVBA, Oud-Turnout, Belgium), Ad libitum
- Water (e.g. ad libitum): Tap-water, ad libitum
- Acclimation period: At least 5 days before the start of treatment under laboratory conditions

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

IN-LIFE DATES: From: Not documented in the report To: Not documented in the report

Administration / exposure

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: Back and or flank
- % coverage: 10% of total body surface (25 cm3 for males and 18 cm3 for females (5X5 cm and 3.5X5 cm, respectively))
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressings were removed and residual test substance was removed using a tissue moistened with tap water.
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg
- Concentration (if solution): No data
- Constant volume or concentration used: yes

Duration of exposure:

Single dose

Doses:

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

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability observed twice daily; Body weight observed on Days 1, 8 and 15; Clinical signs observed periodically on Days 1 and once daily thereafter, until Day 15 (the time of onset, degree and duration were recorded and the symptoms graded according to fixed scales).
- Necropsy of survivors performed: Yes, at the end of the observation period, all animals were sacrificed by asphyxiation using a oxygen/carbon dioxide procedure.

Statistics:

No statistical analysis was performed.

Results and discussion

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: Hunched posture was noted in one male, between days 5-7. Focal erythema, scales, and scabs on the back and/or flank were noted in the majority of animals from day 3-5 onwards. The animals had recoved from the symptoms between days 7 and 14, although scabs

Gross pathology:

No abnormalities were found in the animals at macroscopic post mortem examination.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 for rats treated with a single dermal application was established as exceeding 2000 mg/kg bw as no mortalities were observed.