3,20-bis(ethylenedioxy)pregna-5,7-diene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 May to 16 May, 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: In accordance with OECD and EU guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EEC-Directive 84-449, Annex V, part 84

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,20-bis(ethylenedioxy)pregna-5,7-diene

EC Number:

243-175-0

EC Name:

3,20-bis(ethylenedioxy)pregna-5,7-diene

Cas Number:

19592-55-3

Molecular formula:

C25H36O4

IUPAC Name:

(1S,3aR,9aR,9bS,11aS)-9a,11a-dimethyl-1-(2-methyl-1,3-dioxolan-2-yl)-1,2,3,3a,6,8,9,9a,9b,10,11,11a-dodecahydrospiro[cyclopenta[a]phenanthrene-7,2'-[1,3]dioxolane]

Test material form:

other: crystalline powder

Details on test material:

Off-white crystalline powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Itta Credo-Broekman, B.V., Someren
- Weight at study initiation: 2.5 - 3.0 kg
- Housing: Three rabbits individually housed in stainless steel wire cages KK 102. Sawdust, woodchips, or other extraneous material that might produce skin irritation were excluded.
- Diet (e.g. ad libitum): 80 g food (a standard laboratory diet LKK-20, Hope Farms, Woerden, The Netherlands) per day during the acclimatization period.
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 50-70%
- Air changes (per hr): 16
- Photoperiod: Artificial light from 7 a.m. till 7 p.m.; Radio-sound on 24 hours per day

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hrs.

Observation period:

At 45 minutes and at 20.5, 44 and 68 hours after patch removal, the skin reactions caused by the test substance were scored on the basis of the grades.

Number of animals:

3 male rabbits

Details on study design:

On the last day of the acclimatization period the backs of the three rabbits were clipped free of hair. A single area on each animal was used for the application of the test material. For each animal an occlusive patch was made, that consisted of a layer of gauze, an impermeable layer of Blenderm and a layer of Leukoplast adhesive tape. A sample of 0.5 g proketal was introduced on an area of 6 cm2 of the gauze. In order to establish a procedure with minimal loss of test material, the application procedure varied slightly among the three animals. With respect to animal number 1, test material, moistened with 0.5 ml water, was placed on a dry patch. For the other animals, the patch was moistened with 0.5 ml water before application of test material. The latter procedure was considered to be better. The patches were secured in place by adhesive tape.
The animals were fitted with Elizabethan collars (IMS, Cheshire, UK) in order to prevent disturbance of the application for 4 hours. After this period the collars and patches were removed and the skin was wiped to remove any remaining test substance.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Other effects:

In one rabbit (animal number 2), no hair growth was observed at and around the application site during the study period. Since the initiation of hair growth after shaving is variable in rabbits, this finding was not considered a consequence of treatment with proketal.

Any other information on results incl. tables

In contrast to standard operation procedure TDS 038, the rabbits were not housed in KK100 cages, but in KK 102 cages. In contrast to TDS 038, the application sites were inspected for signs of irritation at approximately 24, 48 and 72 hours after initiation of treatment.This resulted in observation times of approximately 20, 12, 44 and 68 hours after patch removal. In order to establish a procedure with minimal loss of test material, the application procedure varied slightly among the three animals. These deviations were not considered to affect the integrity of the study performed.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A single application of proketal for four hours caused no irritation to the shaven intact skin of male rabbits. According to the standards described in EEC-Directive 83-467, proketal does not need a symbol or a risk phrase with respect to skin irritation.