Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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:
other: Annex V, B6 Magnusson & Kligman
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

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

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Charles River
Sex:
male
Details on test animals and environmental conditions:
Species: Guinea Pig
Strain: Albino Dunkin Hartley
Source: David Hall, Darley Oaks, Newchurch, Burton-on-Trent, Staffordshire, UK.
Sex: Male
Number Used: Twenty test and 10 control
Specificiation: Young Adults
Weight: 386-500g at study initiation

Temperature: 17+/- 2 degC
Relative Humidity: 40-70%
Air: Approximately 25 changes/hour
Light cycle: Artificial, giving 12 hours light, 12 hours dark.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Concentration of test material and vehicle used at induction:
Intradermal injection - 3% w/v in corn oil
Topical induction - 92% w/v in corn oil (highest achievable
concentration)
One day prior to topical induction, 0.5ml of a 10% w/v
preparation of sodium lauryl sulphate in paraffin wax was
applied in order to provoke a mild inflammatory response.
Concentration of test material and vehicle used for each challenge:
92% and 75% in corn oil
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Concentration of test material and vehicle used at induction:
Intradermal injection - 3% w/v in corn oil
Topical induction - 92% w/v in corn oil (highest achievable
concentration)
One day prior to topical induction, 0.5ml of a 10% w/v
preparation of sodium lauryl sulphate in paraffin wax was
applied in order to provoke a mild inflammatory response.
Concentration of test material and vehicle used for each challenge:
92% and 75% in corn oil
No. of animals per dose:
Number of animals in test group: 20
Number of animals in negative control group: 10
Positive control substance(s):
yes

Study design: in vivo (LLNA)

Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
92%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 92%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
92%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 92%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
92%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 92%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
92%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 92%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
Maximum concentration not causing irritating effects in preliminary test: 10 %
Signs of irritation during induction:
No irritation was noted following intradermal injections or
the topical induction.
No irritation was observed in the control animals.
Evidence of sensitisation of each challenge concentration:
92% - Not a Skin Sensitiser. Net response 0%
75% - Not a Skin Sensitiser. Net response 0%
Executive summary:

The sensitisation potential of Dienone was assessed using a method based on the maximisation test described by Magnusson and Kligman (1970). The study involved the treatment of guinea pigs using two procedures: the potential induction of an immune response and a challenge by assessing the degree of erythema.

Following challenge of previously induced guinea pigs with a 92% or a 75% w/v preparation of the test substance in corn oil, no erthematous response was seen on any of hte test or control animals. A positive control study using hexylcinnamaldehyde demonstrated the sensitivity of the test system.

Dienone is not a skin sensitiser under the conditions of the test.

By read across, delta-6 -nandrolone is also not a skin sensitiser under these conditions.