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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:
1998-04-28 - 1998-06-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant study comparable to OECD TG 406 and acceptable for assessment.

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)
Version / remarks:
adopted on 17th July 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Version / remarks:
adopted on 1st July 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
429-460-4
EC Name:
-
Cas Number:
7078-98-0
Molecular formula:
C21 H26 O
IUPAC Name:
2,6-di-tert-butyl-4-(phenylmethylidene)cyclohexa-2,5-dien-1-one

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hilltop Lab Animals, Inc., Scottdale Pennsylvania, U.S.A.
- Age at study initiation: young adult (Hartley-derived albino guinea pigs)
- Weight at study initiation: 366 – 469 g (males), 378 – 470 g (females)
- Housing: housed individually in suspended stainless steel cage
- Diet: PMI Certified Guinea Pig Chow (Purina Mills, Inc.), ad libitum
- Water: Municipal tap water treated by reverse osmosis, ad libitum
- Acclimation period: minimum of five days
Other:
- Only healthy animals were chosen for study use
- Females were nulliparous and nonpregnant

ENVIRONMENTAL CONDITIONS
- Temperature: 61 – 75 °F [ca. 16 – 23 °C] (recorded daily)
- Humidity: 31 -75 % (recorded daily)
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 1998-04-02 To: 1998-05-01

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Intradermal induction: 3 % of test item in in propylene glycol (w/v)
Epidermal induction: 100 % test item
Epidermal challenge: 100 % test item
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
propylene glycol
Concentration / amount:
Intradermal induction: 3 % of test item in in propylene glycol (w/v)
Epidermal induction: 100 % test item
Epidermal challenge: 100 % test item
No. of animals per dose:
10 males /10 females in the test group,
5 males / 5 females in the control group
Details on study design:
RANGE-FINDING TESTS
Pretests were performed for dose-level selection, the results indicated that a test item concentration of 100% was considered appropriate for epidermal/topical induction and challenge. This concentration did induce slight patchy erythema. Discoloration was observed (yellow). Furthermore, an intradermal Range-Finding Study was performed. Due to the dosing difficulties at 5.0 % intradermally and yet similar dermal responses observed at 3.0 %, a test article concentration of 3.0 % (w/w) in propylene glycol was considered appropriate for intradermal induction. As some dermal findings, eschar and blanching at a grade 2 (> 10% to < 25% of test site) were noticed.

MAIN STUDY
A. INDUCTION EXPOSURE
First induction, intradermal injection (day 1):
Three pairs of intradermal injections (0.1 mL per injection) were made simultaneously into the scapular area of each animal as follows:
- FCA emulsion
- Test item (3%) in propylene glycol
- Test item (3%) in propylene glycol / FCA emulsion

Second induction (day 7), epidermal application:
The test item was moistened with 10 drops of propylene glycol prior to application. Then 0.15 g of the test item (100 %) was applied for a period of 48 hours. A patch was applied over the intradermal injection sites and the trunk of each animal was wrapped with elastic wrap which was secured with adhesive tape. The application sites were pretreated the day before with 10% sodium lauryl sulfate (open application).

Control group animals were treated identically in the absence of test item.

B. CHALLENGE EXPOSURE
Test and control group animals were treated (day 21) on the flank with 0.15 g of the test item (100 %) moistened with 10 drops of propylene glycol and the vehicle alone for a period of 24 hours. Skin reactions were scored 24 and 48 hrs after patch removal.
Positive control substance(s):
yes
Remarks:
Alpha-Hexylcinnamaldehyde

Results and discussion

Positive control results:
The positive control item (tested at 5 % during intradermal and topical induction, and at 0.5 % and 1 % during challenge) induced skin sensitising reactions in 40 % of the animals, indicating the sensitivity of the test system.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 16.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 16.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Any other information on results incl. tables

Following challenge with 100 % test item, dermal scores of grade 1 to maximized grade 3 (eschar) were noted in 16/20 test animals (80 % skin sensitising reactions) at the 24-hour and 48-hour scoring interval. Dermal reactions in the remaining test and all challenge control animals were limited to scores of 0. Group mean dermal scores were noted to be higher in the test animals as compared with the challenge control animals.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU