Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to internationally accepted guideline and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):Dienone
- Substance type: off-white powder
- Physical state: solid
- Analytical purity: 99.5% (by DSC)
- Lot/batch No.: Y08696/002 C166/1
- Storage condition of test material: Ambient temperatures in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, UK
- Age at study initiation: young adults, males
- Weight at study initiation:2928-3139g
- Housing: The rabbits were housed individually, in aluminium sheet cages suitable for animals of this strain and the weight range expected during the course of the study. The rabbits were transferred to clean cages and racks, as necessary, during the study.
- Diet (e.g. ad libitum): Diet (Stanrab, SQC), supplied by Special Diet Services Limited, Witham, Essex, UK, ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: at least 6 days prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C):17+/-2 deg C
- Humidity (%): 55+/-15%
- Air changes (per hr):25-30 changes per hour
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From:13 August 1996 To: 18 August 2996

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
Approximately twenty-four hours before application of the test substance, the hair was removed with a pair of veterinary clippers from an area approximately 7cm x 13 cm on the left flank of each animal.

The test substance (approximately 500 mg) was moistened with a small amount (0.3ml) of deionised water to a dry paste to allow good skin contact and, using a metal spatula, was applied to the test site (approximate size 2.5 cmx2.5cm) on the left flank of each rabbit.
Duration of treatment / exposure:
The treated area was covered with a piece of 4-ply surgical gauze (approximate size 2.5 cm x 2.5 cm), which was secured by two strips of surgical tape (approximate size 1cmx8xm). This was covered by a piece of impermeable rubber sheeting (approximate size 35cmx13cm) wrapped once around the trunk of the animal and secured with adhesive impermeable polyethylene tape.

The dressings were left in position for approximately four hours. After this time each dressing was carefully cut (using blunt-tipped scissors), removed and discarded. The application site was gently cleansed free of any residual test substance using clean swabs of absorbent cotton wool soaked in clean warm water and was then dried gently with clean tissue paper. The application site was identified using a black waterproof marker-pen.
Observation period:
Prior to the start of the study, all rabbits were examined to ensure that they were physically normal and exhibited normal activity. Throughout the study, the animals were observed daily for general signs of well being. The Draize scale was used to assess the degree of erythema and oedema at the application sites approximately 30-60 minutes, 1, 2 and 3 days after removal of the dressings. Any other signs of skin irritation were also noted.
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure:2.5x2.5cm
- % coverage:
- Type of wrap if used:The treated area was covered with a piece of 4-ply surgical gauze (approximate size 2.5 cm x 2.5 cm), which was secured by two strips of surgical tape (approximate size 1cmx8xm). This was covered by a piece of impermeable rubber sheeting (approximate size 35cmx13cm) wrapped once around the trunk of the animal and secured with adhesive impermeable polyethylene tape.

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

SCORING SYSTEM:Draize

Results and discussion

In vivo

Results
Irritation parameter:
erythema score
Basis:
animal: two animals
Time point:
other: day of dosing
Remarks on result:
other: very slight erythema
Irritant / corrosive response data:
There were no signs of ill-health in any animal during the study. Very slight erythema was seen on the day of dosing only in two of the animals. No other sigsn of irritation were seen.

Applicant's summary and conclusion

Interpretation of results:
other: practically non-irritating
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
Dienone is practically non-irritant following a single four-hour application to rabbit skin.
Executive summary:

Study Design

A group of 3 male rabbits received a single four-hour application of 500mg Dienone to the shorn flank. The animals were assessed for up to 3 days for any signs of skin irritation.

Results

Very slight erythema was seen on the day of dosing only in two of the animals. No other signs of irritation were seen.

Conclusion

Dienone is practically non-irritant following a single four-hour application to rabbit skin.

By read across, delta-6-nandrolone is also considered non-irritant to rabbit skin.