Registration Dossier

Administrative data

Endpoint:
eye 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 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye 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.:C166/1 Y08696/002


- Storage condition of test material: Ambient temperature in the dark

From the information supplied by the sponsor, the test substance was used within the expiry date. A certificate of analysis is retained in the CTL Archives.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, UK
- Age at study initiation: young adults
- Weight at study initiation: 2446-3104 g
- 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

Vehicle:
not specified
Controls:
other: each animal was it's own control, one eye treated, one not.
Amount / concentration applied:
100 mg was applied into the conjunctival sac of the left eye of one rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped.
Duration of treatment / exposure:
The lids were then gently held together for 1-2 seconds after which the animal was released. The other eye was untreated (control).
Observation period (in vivo):
3 Days after application
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: fluorescein staining was used at all readings from 1 day after application.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72h
Score:
0
Max. score:
10
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 2hrs
Score:
6
Max. score:
20
Reversibility:
fully reversible within: 72h
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72h
Score:
0
Max. score:
80
Reversibility:
not specified
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 2h
Score:
6
Max. score:
110
Reversibility:
fully reversible within: 72h
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24h
Score:
3.3
Max. score:
110
Reversibility:
not specified
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48h
Score:
1.3
Max. score:
110
Reversibility:
not specified
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 72h
Score:
0
Max. score:
110
Reversibility:
not specified

Applicant's summary and conclusion

Interpretation of results:
other: Mild Irritant (Class 4)
Conclusions:
Dienone is a mild irritant (class 4 on a 1-8 scale) to the rabbit eye.
Executive summary:

Study design

Dienone (100 mg) was applied into one eye of each of three rabbits and an assessment of initial pain was made.

 The eyes were examined for up to 3 days, to assess the grade of ocular reaction. 

 

Results

Application into the eye caused practically no, or slight initial pain (class 1 to 2 on a 0-5 scale). Approximately ¼ to 1/3 of the test substance was displaced from the eye immediately after dosing.

 No corneal or iridial effects were observed. Conjunctival effects were limited to slight redness, slight chemosis and slight to moderate discharge, which had completely regressed by day 3. 

 

No other signs of irritation were seen.

 

Conclusion

 Dienone is a mild irritant (class 4 on a 1-8 scale) to the rabbit eye.

By read across, delta-6 -nandrolone is considered a mild eye irritant.