Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting 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:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
max applied dose = 2000mg/kg
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
max applied dose = 2000mg/kg
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
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

Species:
rat
Strain:
other: Alpk:APfSD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Rodent Breeding Unit, Alderly Park, Macclesfield, Cheshire, UK.
- Age at study initiation: 8-12 weesk
- Weight at study initiation: Males: 389-431 Females: 182-219
- Fasting period before study: not specified
- Housing:The rats were housed individually, in multiple
- Diet (e.g. ad libitum): R&M No.1, supplied by Special Diet Services Limited, Witham, Essex, UK, ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period:6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22+/- 4 deg C
- Humidity (%):30-70
- Air changes (per hr):15 per hour
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: enough water to make a paste
Details on dermal exposure:
TEST SITE
- Area of exposure: 7cmx7 cm
- % coverage:
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):males- 16.0-23.8 mg/cm2; females:10-12.5 mg/cm2
- Concentration (if solution):

- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit):0.4-0.7 ml water
Duration of exposure:
24 h
Doses:
2000mg/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 d
- Frequency of observations and weighing: before dosing and also Day 8 and 15.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight. macroscopic post mortem examination. This inviovled an external observation and a careful examination of all thoracic and abdominal viscera.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

Applicant's summary and conclusion

Conclusions:
The acute dermal median lethal dose of dienone is greater than 2000mg/kg to male and female rats.
Executive summary:

A group of five male and five female Alpk:APfSD (Wistar-derived) rats received a single dermal application of 2000 mg/kg of dienone. 

 

The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their bodyweights were recorded at intervals throughout the study. At the end of the study, all the animals were killed and subjected to a macroscopic examination post mortem.

 

Results

 

None of the animals died and there were significant signs of systemic toxicity and no signs of skin irritation in any animal. All animals showed an overall weight gain during the study. There were no macroscopic abnormalities in any animal at examination post mortem.

 

Conclusion

The acute dermal median lethal dose of dienone is in excess of 2000 mg/kg to male and female rats.

By read across, the median lethal dose of delta-6 -nandrolone is also in excess of 2000 mg/kg.