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

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-01-16 to 2013-02-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: A GLP study conducted to current accepted testing guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

Temporary deviations from the minimum level of daily mean relative humidity occurred. Evaluation: Laboratory historical data do not indicate an effect of the deviations. The study integrity was not adversely affected by the deviations.

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

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:

solid: crystalline

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Healthy mice (CBA/J strain, inbred, SPF-Quality) were used as the test system. This strain of mice is recognized by the international guidelines as the recommended test system (e.g. OECD, EC, EPA). Females were nulliparous and non-pregnant. The animals were provided by Janvier, Le Genest-Saint-Isle, France.
A total of 20 females were used, 5 females per group (approximately 9 weeks old at start of treatment).

Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Concentration:

10, 25 or 50% w/w

No. of animals per dose:

Five animals/dose

Details on study design:

Three experimental groups of five female CBA/J mice were treated with test substance concentrations of 10, 25 or 50% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated with vehicle alone (propylene glycol), on three consecutive days, by open application on the ears.

Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of Disintegrations Per Minute (DPM) and a stimulation index (SI) was subsequently calculated for each group.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The six-month reliability check with Alpha-hexylcinnamicaldehyde indicates that the Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing for contact hypersensitivity

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

>= 0 - <= 3

Test group / Remarks:

5 mice at 10%,

Remarks on result:

not determinable

Remarks:

no result > 3 up to 50%

Results 2

Parameter:

SI

Value:

>= 0 - <= 3

Test group / Remarks:

5 mice at 25%

Remarks on result:

not determinable

Remarks:

no result >3 up to 50%

Results 3

Parameter:

SI

Value:

>= 0 - <= 3

Test group / Remarks:

5 mice at 50%

Remarks on result:

not determinable

Remarks:

no result >3 up to 50%

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Since there was no indication that the test substance elicits an SI ≥ 3 when tested up to 50%, Proketal was considered not to be a skin sensitizer.

Based on these results, Proketal would not be regarded as a skin sensitizer according to the recommendations made in the test guidelines.