Estr-5(10)-en-3-one, 17-hydroxy-, (17.beta.)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb 2006 - Mar 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

A combined study on acute dermal toxicity and on local tolerance was used to assess skin irritation/corrosion. The study design and reporting deviates from the current OECD TG 404, however, the study is considered sufficient for assessment of this endpoint.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

exposure time 24 hrs instead of 4 hrs, 6 animals instead of 3, rats instead of rabbits, few details in test description and reporting

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

17 beta-Hydroxy-5(10)-estren-3-one

EC Number:

600-891-1

Cas Number:

1089-78-7

Molecular formula:

C18 H26 O2

IUPAC Name:

17 beta-Hydroxy-5(10)-estren-3-one

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Han:WIST

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: no data
- Weight at study initiation: males (238 - 250 g); females (201 - 208 g)
- Fasting period before study: no data
- Housing: one per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: ≥ 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- Humidity (%): 54 - 58
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

physiological saline

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 477-499 mg (male animals), 402-421 mg (female animals)

VEHICLE
- Amount(s) applied: 0.7 mL
- Concentration: 0.9%
- Lot/batch no. : 4342A191
- Purity: no data

Duration of treatment / exposure:

24 h

Observation period:

The application sites were evaluated 1, 24, 48 and 72 h after removal of the patches.

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 4 x 9 cm
- % coverage: approximately 10% of the body surface area of a rat
- Type of wrap: gauze

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

OBSERVATION TIME POINTS: 1, 24, 48, 72/74 hours (The evaluation of the application sites of the male animals was performed 2 hours later on day 5 (i.e. 72 hours after removal of the patches). This deviation is not considered to have a relevant influence to the study result because all animals were without local findings also on the earlier time points.

SCORING SYSTEM:
- Method of calculation: The scoring system recommended by the EU (Amendment of the Directive 67/548/EEC, Annex V, B.4. Acute toxicity (Skin irritation) in the version of the Directive 92/69/EEC, dated 31 Jul 1992.)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after administration were 0 for swelling, reddening and scab formation after administration of 2000 mg/kg test substance.

Other effects:

A single dermal administration of the test substance to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, compound-related clinical findings and gross pathological findings. After administration of the test substance a slight decrease in body weight was observed in all male animals and one female animal on day 7 of the study. This effect was reversible on day 14.

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Remarks:

in opinion of study director

Executive summary:

A combined study on acute dermal toxicity and on local tolerance was conducted . The study design and reporting deviates from the current OECD TG 404, however, the study was considered sufficient for assessment of skin irritation/corrosion. A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg did not show irritating potential.