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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-02-11 to 1998-03-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive and done to a valid guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
In vivo study that was performed before 10 May 2017

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl (3aR,7R,7aR)-2,2-dimethyl-7-[(methylsulfonyl)oxy]-3a,6,7,7a-tetrahydro-1,3-benzodioxole-5-carboxylate
EC Number:
606-548-2
Cas Number:
204254-84-2
Molecular formula:
C13 H20 O7 S
IUPAC Name:
Ethyl (3aR,7R,7aR)-2,2-dimethyl-7-[(methylsulfonyl)oxy]-3a,6,7,7a-tetrahydro-1,3-benzodioxole-5-carboxylate
Test material form:
other: solid
Details on test material:
Purity: unknown
Retest date: 17 October 1998

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Ibm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted)
Sex:
female
Details on test animals and environmental conditions:
Age at pre-test: 4-6 weeks, (nulliparous and non-pregnant females)
Body weight at pre-test: 396-420 g (pre-test groups)
Body weight at beginning of acclimatization period: 317-441g
Standard Laboratory Conditions
Air-conditioned with 10-15 air changes per hour and continuously monitored environment with a target range for room temperature of 22 ± 3 °C and for relative humidity between 40-70 % (values above 70 % during cleaning process possible). The animals were provided with a 12-hour light, 12-hour dark cycle. Music was played during the light period.
Pelleted diet and access to community tap water.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
polyethylene glycol
Concentration / amount:
Intradermal injections (Day 1): 5% in PEG400
Epidermal Applications (Day 8): 50% in PEG 400
Challenge (Day 22): 25% in PEG 400
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
Intradermal injections (Day 1): 5% in PEG400
Epidermal Applications (Day 8): 50% in PEG 400
Challenge (Day 22): 25% in PEG 400
No. of animals per dose:
10 (test group), 5 (control group)
Details on study design:
Group 1, Control group, 5 animals
Group 2, Test group, 10 animals
Group 3, Intradermal pretest group, 1 animal
Group 4, Epidermal pretest group, 2 animals
PEG 400 was used for the intradermal and epidermal pretests. It was also used for the intradermal and epidermal induction and the challenge in the main study. The 1:1 mixture (v/v) of Freund’s Complete Adjuvant: physiological saline was used as vehicle for the pretest and the intradermal induction in the main study.
Test Day 1 - Intradermal Injections:
An area of dorsal skin from the scapular region (approximately 6 x 8 cm) was clipped free of hair. Three pairs of intradermal injections (0.1 ml/site) were made at the border of a 4 x 6 cm area in the clipped region as follows:
Test Group 1. a 1:1 (v/v) mixture of Freund’s Complete Adjuvant and physiological saline
Test Group 2. The test item (5% in PEG 400)
Test Group 3. The test item diluted to 5 % by emulsion in a 1:1 (v/v) mixture of Freund’s Complete Adjuvant and physiological saline
Control Group 1.a 1:1 (v/v) mixture of Freund’s Complete Adjuvant and physiological saline
Control Group 2. PEG 400
Control Group 3. 1:1 (w/w) mixture of PEG 400 in a 1:1 (v/v) mixture of Freund’s Complete Adjuvant and physiological saline.
Test Day 8 - Epidermal Applications
On test day 7 and approximately 24 hours prior to the epidermal application the scapular area (approximately 6 x 8 cm) of the animals of the control and test group was clipped, shaved free of hair and the test area was pretreated with a 10 % dilution of Sodium-Lauryl-Sulfate (SLS) in paraffinum perliquidum as no primary irritation had been observed in the pretest. The SLS was massaged into the skin with a glass rod without bandaging. This 10 % concentration of SLS enhances sensitization by provoking a mild inflammatory reaction (Magnusson and Kligman 1970).
On test day 8, a 2 x 4 cm patch of filter paper was saturated with the test article (50 % in PEG 400) and placed between the injection sites of the test animals. The volume of test article applied was approximately 0.3 g. The patch was covered with aluminum foil and firmly secured by an elastic plaster wrapped around the trunk of the animal and secured with impervious adhesive tape. The dressings were left in place for 48 hours. The epidermal application procedure described ensured intensive contact of the test article.
The guinea pigs of the control group were treated as described above with PEG 400 only. The volume applied was approximately 0.3 ml. Reaction sites were assessed for erythema and oedema 24 and 48 hours after removal of the dressing, using the numerical grading system according to Draize.
Challenge on Test Day 22
The test and control guinea pigs were challenged two weeks after the epidermal induction application. The test and control guinea pigs were treated in the same way. Hair was clipped and shaved from a 5 x 5 cm area on the left and right flank of each guinea pig just prior to the application. Two patches (2 x 2 cm) of filter paper were saturated with the highest non-irritating concentration of 25 % (left flank) and the vehicle only (PEG 400 applied to the right flank) using the same method as for the epidermal application. The volume of test article applied was approximately 0.2 ml. The dressings were left in place for 24 hours. Approximately 21 hours after removal of the dressing the test sites treated with the test article were depilated as described in the epidermal pretest. Approximately 24 and 48 hours after the removal of the dressing the application sites were assessed for erythema and oedema using the numerical scoring system according to Draize.
Challenge controls:
The challenge site was evaluated 24 and 48 hours after the removal of the patch. The readings were made under artificial fluorescent light (daylight spectrum). Redness constitutes the minimum criterion of an allergic reaction. Strongly sensitized animals display a vivid redness, associated with indurated swelling. The reactions were scored on the basis of the Draize score described under "Readings and Scoring".
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole

Results and discussion

Positive control results:
The positive control, 2-Mercaptobenzothiazole, was assessed outside of this study.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% in PEG 400
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% in PEG 400. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% in PEG 400
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% in PEG 400. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
PEG 400 only
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: PEG 400 only. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
PEG 400 only
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: PEG 400 only. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other: EEC
Conclusions:
The test article applied at a concentration of 25 % in PEG 400 is considered not to be a sensitizer when used under the described test conditions.
Executive summary:

In order to assess the cutaneous allergenic potential of the test item, the Maximization- Test was performed in 15 (10 test and 5 control) female albino guinea pigs, in accordance with OECD Guideline No. 406 and the Directive 96/54/EEC, B.6. The intradermal induction of sensitization was performed with a 5 % dilution of the test article in polyethylene glycol (PEG 400) and in an emulsion of Freund’s Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted under occlusion with the test article at 50 % in PEG 400. Two weeks after the epidermal induction application the challenge was completed by epidermal application of the test article at 25 % in PEG 400 under occlusive dressing. The animals of the control group were induced with PEG 400 and FCA/physiological saline and challenged similarly to those of the test group. Cutaneous reactions, i.e. erythema and eschar, as well as oedema formation were evaluated at 24 and 48 hours after removal of the dressing.

In this study none of the test animals were observed with positive skin reactions after treatment with a non-irritant test article concentration of 25 % in PEG 400. No skin reactions were observed in the control group.

Therefore, the test article applied at a concentration of 25 % in PEG 400 is considered not to be a sensitizer when used under the described test conditions.