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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Feb to Mar 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
17 July 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The guinea pig maximisation test was an adequate in vivo skin sensitisation test at the time of performance in 2000.

Test material

Constituent 1
Chemical structure
Reference substance name:
3,3-Dimethoxyestr-5(10)-en-17-one
EC Number:
606-278-5
Cas Number:
19257-34-2
Molecular formula:
C20 H30 O3
IUPAC Name:
3,3-Dimethoxyestr-5(10)-en-17-one

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Dunkin Hartley Pirbright White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Kislegg, Germany
- Weight at study initiation: male: 335 - 435 g; female: 334 - 383 g
- Housing: 1 or 2 in conventional Makrolon®, type IV cages
- Diet (e.g. ad libitum): pell. Altromin®MS, apple, hay ad libitum
- Water (e.g. ad libitum): demineralized acidified water, pH 2 - 3 ad libitum
- Acclimation period: ≥ 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 42-62
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: liquid paraffin
Concentration / amount:
25%
Day(s)/duration:
treatment for 48h with a pause of 12 days until Challenge
Challenge
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
25%
Day(s)/duration:
24h
No. of animals per dose:
control group: 10 (5/sex)
test substance group: 10 (5/sex)
Details on study design:
RANGE FINDING TESTS:
A local tolerance study (pretest) was performed to ensure an intracutaneously tolerable concentration without any necrosis for the induction procedure (reddening and swelling are accepted). The maximum concentration intended to be used in the present test for intracutaneous administration was 5% which is the concentration recommended as maximum concentration when tolerated. Each applicable concentration was applied at 2 different administration sites (one on the left, one on the right side) in the neck. The reactions were recorded 24 hours after administration. Furthermore, an epicutaneously tolerable concentration for epidermal administration in the induction procedure and for epidermal challenge was determined. Filter papers with 0.2 mL of the test formulations (25% and 12.5%) were epidermally applied under occlusive conditions for 24 hours. 25% as high concentration is the recommended maximum concentration for induction procedures, provided that the treatment produces no excessive irritation. As a concentration is recommended for challenge which is tolerated without any local reactions, a second concentration of 12.5% was tested. The reactions were recorded 24 hours after removal of the filter papers.
The intracutaneous administration of 0.1 mL of a 5% (w/v) oily formulation of the test item in the neck region provoked only slight findings but no necrosis. Therefore, for induction this concentration was used. The epidermal administration of 0.2 mL of a formulation with 25% (w/v) of the test item was
tolerated without findings. Therefore, for induction and for challenge procedure a concentration of 25% (w/v) of the test item was used.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Two, intracutaneous and epidermal (day 9)
- Exposure period: epidermal 48h
- Test groups: One treatment group and one vehicle group
- Control group: vehicle group
- Site: neck region (right to left side of the spine); 4 x 6 cm
- Frequency of applications: once for intradermal and epidermal administration
- Duration:
- Concentrations: intradermal 0.1 mL 5 % (w/v) and 0.1 mL [10% (w/v) test item+ FCA (1+1)] = 5 % (w/v)
epidermal: 0.2 mL of 25% (w/v) suspension

B. CHALLENGE EXPOSURE
- No. of exposures: Once
- Day(s) of challenge: 23
- Exposure period: 24 h
- Test groups: 25% (w/v)
- Control group: 0.2 mL of liquid paraffin only
- Site: neck region (right to left side of the spine)
- Concentrations: 25% (w/v)
- Evaluation (hr after challenge): 24 and 48 h

Positive control substance(s):
yes
Remarks:
The contact-sensitizing potential were checked with the positive reference compound mercaptobenzothiazole or synonymous 1, 2-Benzisothiazole-3-thiol in the year before the test.

Results and discussion

Positive control results:
9 out of 10 guinea-pigs showed signs of contact-sensitization, proving the reliability of the test procedure and the sensitivity of the guinea-pig strain used.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
positive control with mercaptobenzothiazole
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
not measured/tested
Remarks:
A concurrent positive control was not used in the present test
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
challenge 25 %
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
slight reddening
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
challenge 25 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
negative control/vehicle
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
negative control/vehicle
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none

Any other information on results incl. tables

In the test group slight reddening was found in one out of 10 animals 24 hours after the end of exposure, whereas in the remaining 9 out of 10 animals of the test group and in all animals of the control no local skin reaction was observed at either time point.
Due to the low incidence of findings (the difference in the number of animals with findings between test and control group was not significant at the time point 24 hours after the end of exposure) and due to the slight grade of the finding in one animal, this finding is regarded as incidental in nature and not as indicative of any contact-sensitizing potential of the test item.

Applicant's summary and conclusion

Conclusions:
In a guinea pig maximization test (GPMT) according to OECD TG 406 no skin sensitizing potential of the test substance could be observed based on the results after challenge with 25 % test item.
Executive summary:

In a dermal sensitization study according to OECD TG 406 (17 July 1992) with Dimethoxyketal 5%(w/v), young adult female/male guinea pigs (Dunkin Harley Pirbright White) (5/sex/dose) were tested in the GPMT (OECD TG 406). For induction the animals were treated either intracutaneous with 0.1 mL of diluted (1 + 1 with vehicle) Freund´s complete adjuvant (FCA), test item [5% (w/v)] or test item [5% (w/v)] diluted 1 + 1 with FCA into the right and left dorsal neck region on study day 1. In the same way, the control group (5 male, 5 female) received 0.1 mL of the vehicle [liquid paraffin] with and without FCA. n day 9, the same area of skin was covered with a filter paper impregnated with the test item [25% (w/v) in liquid paraffin] for the test group, or impregnated with liquid paraffin for the controls. On day 23, as a challenge, the same procedure was followed as on day 9, but the controls also received the filter paper impregnated with the test item [25% (w/v)] in liquid paraffin. The application was made in the more sensitive flank region.
In the test group slight reddening was found in one out of 10 animals 24 hours after the end of exposure, whereas in the remaining 9 out of 10 animals of the test group and in all animals of the control no local skin reaction was observed at either time point.
Due to the low incidence of findings (the difference in the number of animals with findings between test and control group was not significant at the time point 24 hours after the end of exposure) and due to the slight grade of the finding in one animal, this finding is regarded as incidental in nature and not as indicative of any contact-sensitizing potential of the test item.