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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:
weight of evidence
Study period:
June 1998 - November 1998
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to guideline, however, it did not test the sensitisation potential of the registered substance. The negative control substance used in the study is the registered substance.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
The negative control substance used in the study is the registered substance.
Principles of method if other than guideline:
The registration substance, 1,1,3,3-tetramethyl-1,3-divinyldisiloxane (CAS 2627-95-4) is the negative (vehicle) control used in the study.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: Vehicle control: 1,1,3,3-tetramethyl-1,3-divinyldisiloxane Positive control vehicle: propylene glycol
Concentration / amount:
test group animals: 5% test substance in the vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane); saline/FCA; test substance/FCA/saline
vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) control group: 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane); saline/FCA; vehicle/FCA/saline
positive control group animals: DNCB/PG (propylene glycol); saline/FCA; DNCB/FCA/saline
crosslinker (CL) control group: CL/Vehicle; saline/FCA; CL/FCA/saline
Day(s)/duration:
single intradermal injection
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: Vehicle control: 1,1,3,3-tetramethyl-1,3-divinyldisiloxane Positive control vehicle: propylene glycol
Concentration / amount:
test group animals: 100% test substance
vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) control group: 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane)
positive control group animals: 0.1% DNCB in propylene glycol (PG)
crosslinker (CL) control group: 100% test substance
Day(s)/duration:
48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Vehicle control: 1,1,3,3-tetramethyl-1,3-divinyldisiloxane Positive control vehicle: propylene glycol
Concentration / amount:
- Test group: 100% test substance and 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane)
- Vehicle control group: 100% test substance and 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane)
- Positive control group: 0.1% DNCB/PG and 100% PG
- Crosslinker controls: 100% CL substance and 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane)
Day(s)/duration:
24 hours
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: Vehicle control: 1,1,3,3-tetramethyl-1,3-divinyldisiloxane Positive control vehicle: propylene glycol
Concentration / amount:
- Test group: 50% test substance and 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane)
- Vehicle control group: 50% test substance and 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane)
- Crosslinker controls: 50% CL substance and 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane)
Day(s)/duration:
24 hours
No. of animals per dose:
20 test substance, 10 vehicle control, 10 positive control, 10 crosslinker control
Details on study design:
RANGE FINDING TESTS:
Based on the preliminary topical applications, a 5% test substance in the vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was found to be the optimal concentration for the first (intradermal) induction, undiluted (100%) TS for the second induction and the first challenge and a 50% test substance in the vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) for the second challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal induction on day 1 followed by a topical induction on day 8)
- Exposure period: Intradermal induction on day 1 followed by a topical induction on day 8

INTRADERMAL INDUCTION: The first induction was performed on day 1, when the fur over the scapula of each animal in an area of approximately 4x6 cm was shaved and six intradermal injections (three pairs) of 0.1 ml of the dosing formulations were made flanking the dorsal midline.

The following intradermal injections were made on the test group animals:
- left dorsal flank: 5% test substance in the vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane); saline/FCA; test substance/FCA/saline
- right flank: 5% test substance in vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane); saline/FCA; test substance/FCA/saline

The following intradermal injections were made on the vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) control group:
- left dorsal flank: 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane); saline/FCA; vehicle/FCA/saline
- right flank: 100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane); saline/FCA; vehicle/FCA/saline

The following intradermal injections were made on the positive control group animals:
- left dorsal flank: DNCB/PG (propylene glycol); saline/FCA; DNCB/FCA/saline
- right flank: DNCB/PG; saline/FCA; DNCB/FCA/saline

The following intradermal injections were made on the crosslinker (CL) control group animals:
- left dorsal flank: CL (different substannce)/Vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane); saline/FCA; CL/FCA/saline
- right flank: CL (different substannce)/Vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane); saline/FCA; CL/FCA/saline

TOPICAL INDUCTION: Since no signs of dermal irritation were observed using several different concentrations of the test substance during the preliminary study, the area of that had received the i.d. injections was shaved and 0.5 ml of a 10% aqueous SLS formulation was applied on day 7 to induce dermal irritation. On day 8 topical induction was performed on the test, vehicle control and positive control animals. The test item or control substances were applied onto the dorsal flanks for 48 hours.
- The neat test substance was applied topically over the six injection sites of each test-substance-treated animals or crosslinker animals.
- Undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied on the flanks of vehicle control animals
- 0.1% DNCB in propylene glycol (PG) was applied onto the flanks of the positive control animals.


B. CHALLENGE EXPOSURE

FIRST CHALLENGE: On day 22, two weeks following the application of the last induction dose. Applied for 24 hours. Sensitisation reactions were evaluated at 24 and 48 hours
- Test group: 0.3 ml of 100% test substance formulation was applied to the shaved upper left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved upper right flank of each of the 20 test group animals.
- Vehicle control group: 0.3 ml of 100% test substance formulation was applied to the shaved upper left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved upper right flank of each of the 20 test group animals.
- Positive control group: 0.3 ml of 0.1% DNCB/PG were applied on the upper left flank and 100% PG was applied on the upper right flank.
- Crosslinker controls: 0.3 ml of 100% CL substance formulation was applied to the shaved upper left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved upper right flank of each of the 20 test group animals.

SECOND CHALLENGE: On day 29, one week following the first challenge dosing. Applied for 24 hours. Sensitisation reactions were evaluated at 24 and 48 hours. Second challenge was performed for the test, vehicle control and crosslinker control groups.
- Test group: 0.3 ml of 50% test substance formulation was applied to the shaved lower left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved lower right flank of each of the 20 test group animals.
- Vehicle control group: 0.3 ml of 50% test substance formulation was applied to the shaved lower left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved lower right flank of each of the 20 test group animals.
- Crosslinker controls: 0.3 ml of 50% CL substance formulation was applied to the shaved lower left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved lower right flank of each of the 20 test group animals.
Challenge controls:
FIRST CHALLENGE:
- Vehicle control group: 0.3 ml of 100% test substance formulation was applied to the shaved upper left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved upper right flank of each of the 20 test group animals.
- Positive control group: 0.3 ml of 0.1% DNCB/PG were applied on the upper left flank and 100% PG was applied on the upper right flank.
- Crosslinker controls: 0.3 ml of 100% CL substance formulation was applied to the shaved upper left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved upper right flank of each of the 20 test group animals.
SECOND CHALLENGE:
- Vehicle control group: 0.3 ml of 50% test substance formulation was applied to the shaved lower left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved lower right flank of each of the 20 test group animals.
- Crosslinker controls: 0.3 ml of 50% CL substance formulation was applied to the shaved lower left flank and 0.3 ml of the undiluted vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) was applied to the shaved lower right flank of each of the 20 test group animals.
Positive control substance(s):
yes
Remarks:
DNCB

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100% test substance on the left flank
No. with + reactions:
7
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100% test substance on the left flank
No. with + reactions:
11
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% test substance on the left flank
No. with + reactions:
10
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% test substance on the left flank
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% test substance on the left flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% test substance on the left flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% test substance on the left flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% test substance on the left flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% DNCB/PG on the left flank
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1% DNCB/PG were applied on the upper left flank
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
100% propylene glycol on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
100% propylene glycol on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
other: crosslinker control
Dose level:
100% CL substance on the left flank
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
other: crosslinker control
Dose level:
100% CL substance on the left flank
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
other: crosslinker control
Dose level:
50% CL substance on the left flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
other: crosslinker control
Dose level:
50% CL substance on the left flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
other: crosslinker control
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
other: crosslinker control
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
other: crosslinker control
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
other: crosslinker controls
Dose level:
100% vehicle (1,1,3,3-tetramethyl-1,3-divinyldisiloxane) on the right flank
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
The registration substance, 1,1,3,3-tetramethyl-1,3-divinyldisiloxane (CAS 2627-95-4) was used as the negative (vehicle) control in the study and was concluded to be not a sensitising to skin.
Conclusions:
In the in vivo skin sensitisation study, conducted according to OECD Test Guideline 406 and in compliance with GLP, the negative/vehicle control substance used is the registration substance, 1,1,3,3-tetramethyl-1,3-divinyldisiloxane (CAS 2627-95-4). The substance was concluded to be not sensitising to skin when applied undiluted during the first and second challenge.