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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:
19 October 1987 to 13 November 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in accordance with an acceptable scientific method.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In the maximization test the intensity of local reactions in guinea pigs after an epidermal administration (challenge) of the test compound in animals which have undergone a sensitizing treatment procedure with this compound (induction), is compared with animals which have undergone the same induction procedure with the vehicle only and serve as controls. Any clear cut stronger reaction in animals treated with ZK 119.649 should be regarded as indicative of a sensitizing potential of the test compound.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The LLNA 429 was not formally adopted by the OECD until 22 July 2010.

Test material

Constituent 1
Chemical structure
Reference substance name:
Isobutylisopropyldimethoxysilane
EC Number:
402-580-4
EC Name:
Isobutylisopropyldimethoxysilane
Cas Number:
111439-76-0
Molecular formula:
Hill formula: C9H22O2Si
IUPAC Name:
dimethoxy(2-methylpropyl)(propan-2-yl)silane
Details on test material:
ZK 119.649 (TZ 01748)
IUPAC name: Dimethoxyisobutylisopropylsilane
Batch No.: W87/75-82

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
female
Details on test animals and environmental conditions:
Number of animals and strain: 20 Pirbright White guinea pigs
Breeder: Hagemann
Acclimatization time: > 18 days
Caging condition:conventional
Cage type: Makrolon, type III
Animals per cage: 2
Number of groups: 2, 5M/5F each
Body weight: F: 327-421 g, M: 330-447 g
Feed type: pell. Altromin MS
Feeding time: ad libitum
Type of drinking water: tap water
Watering time: ad libitum
Room temperature: 21-22°C
Relative humidity: 48-64%
Light period: 12 hours day-night cycle
Randomization: by lot
Identification: by ear marks and ear cuts

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
peanut oil
Concentration / amount:
Induction procedure:
Intradermal injection (Test group):
a) 0.1 ml complete Freund's adjuvant + vehicle (1+1)
b) 0.1 ml ZK 119.649; 25% w/v
c) 0.1 ml ZK 119.649; 50% w/v + complete Freund's adjuvant (1+1) = 25% w/v of ZK 119.649
Epidermal: original formulation of ZK 119.649
Challenge epidermal: 0.1 ml ZK 119.649 (50% w/v) in peanut-oil
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
peanut oil
Concentration / amount:
Induction procedure:
Intradermal injection (Test group):
a) 0.1 ml complete Freund's adjuvant + vehicle (1+1)
b) 0.1 ml ZK 119.649; 25% w/v
c) 0.1 ml ZK 119.649; 50% w/v + complete Freund's adjuvant (1+1) = 25% w/v of ZK 119.649
Epidermal: original formulation of ZK 119.649
Challenge epidermal: 0.1 ml ZK 119.649 (50% w/v) in peanut-oil
No. of animals per dose:
5 male + 5 female
Details on study design:
Induction procedure

Intradermal injections
In the neck region (right and left side of the spine) of each animal an overall area of 4 x 6 cm was shorn (10M/10F). A total of 6 intradermal injections, 3 on each side, were made. The 3 on each side were as follows:

A. Test group
a) 0.1 ml complete Freund's adjuvant + vehicle (1+1)
b) 0.1 ml ZK 119.649; 25% w/v
c) 0.1 ml ZK 119.649; 50% w/v + complete Freund's adjuvant (1+1) = 25% w/v of ZK 119.649
B. Control group
a) 0.1 ml Freund's complete adjuvant + vehicle (1+1)
b) 0.1 ml vehicle
c) 0.1 ml Freund's complete adjuvant + vehicle (1+1)

The injections were set within an area of 2 x 4 cm. The above mentioned concentration of ZK 119.649 did not produce necrosis and ulcerations in the guinea pigs after intradermal application in the same region as was previously proved.

Epidermal application
In order to favour the sensitizing effect of ZK 119.649, the same area of skin ( 4 x 6 cm) in which intradermal injections were performed, was reshaved on day 8 of the test and epidermally treated with approximately 1 ml sodium lauryl sulphate (10 %w/v) in liquid paraffin. 24 hours later, on day 9, 0.1 ml of original formulation of ZK 119.649 was spread over a 2 x 4 cm filter paper (Whatmann, no. 3MM) for the use in the test group, whereas for
the control group only peanuts-oil was used. Then, this filter paper was applied on the above mentioned area pretreated with sodium lauryl sulphate. The patch was bandaged occlusively for 48 hours. The original formulation of ZK 119.649 was previously proved to provoke no necrosis to the skin after epidermal administration under occlusion.

Challenge procedure
On day 23 (two weeks after the epidermal administration) a skin area of 5 x 5 cm was shorn on the right flank of each animal in both groups.
0.1 ml ZK 119.649 (50% w/v) in peanut-oil which previously proved to be locally tolerated was spread over a 2 x 2 cm piece of filter paper. This patch was placed in the middle of the shorn area of skin and bandaged occlusively for 24 hours. Reactions were recorded 24 and 48 hours after removal of the bandage. 3 hours prior to the first reading the test area was carefully shorn.

Reading and recording of local reactions
48 and 72 hours after the epidermal administration of ZK 119.649 (50% w/v) suspended in peanuts-oil in the right flank region in all animals (test group and control group), i.e. 24 and 48 hours after the occlusive bandage was removed, the local reactions were recorded according to the following scheme:

0 = neither reddening nor swelling
1 = slight reddening
2 = mild reddening
3 = severe reddening
4 = slight swelling
5 = mild swelling
6 = severe swelling
additional findings

Evaluation of findings
The types and the number of reactions in both groups were compared visually. Any clear cut increase in the animals treated with the test compound in comparison to the controls was considered as indicative of a sensitizing potential of the test compound in guinea pigs.
Challenge controls:
No challenge controls.
For the challenge, induction controls also received the filter paper impregnated with ZK 119.649 (50% w/v) in peanut-oil.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
ZK 119.649 (50% w/v) in peanut-oil.
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: ZK 119.649 (50% w/v) in peanut-oil.. 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:
ZK 119.649 (50% w/v) in peanut-oil.
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: ZK 119.649 (50% w/v) in peanut-oil.. 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:
Not applicable
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: negative control. Dose level: Not applicable. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Not applicable
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: negative control. Dose level: Not applicable. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
ZK 119.649 proved to be non-sensitising in guinea pigs in the maximization test.
Executive summary:

The sensitising potential of the test substance was evaluated using the guinea pig maximisation test.

ZK 119.649 proved to be non-sensitising in guinea pigs in the maximization test.