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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:
23 January - 27 April, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
An LLNA study was not performed because the test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(trimethoxysilyl)propyl (2E,4E)-hexa-2,4-dienoate
EC Number:
642-902-2
Cas Number:
163802-53-7
Molecular formula:
C12H22O5Si
IUPAC Name:
3-(trimethoxysilyl)propyl (2E,4E)-hexa-2,4-dienoate
Constituent 2
Reference substance name:
2,4-Hexadienoic acid, 3-(trimethoxysilyl)propyl ester, (2E,4E)-
IUPAC Name:
2,4-Hexadienoic acid, 3-(trimethoxysilyl)propyl ester, (2E,4E)-
Constituent 3
Reference substance name:
3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate
IUPAC Name:
3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate
Test material form:
liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Crl: HA
Sex:
female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Remarks:
(Preliminary Irritancy Testing)
Concentration / amount:
Test animals:
Induction: 100 %
Challenge: 100 %

Negative control animals: dry patch
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Remarks:
(Preliminary Irritancy Testing)
Concentration / amount:
Test animals:
Induction: 100 %
Challenge: 100 %

Negative control animals: dry patch
No. of animals per dose:
Test animals: 20
Negative control animals: 10
Details on study design:
RANGE FINDING TESTS:
The chosen concentrations were 25 %, 50 %, 75 % and 100 %, and the vehicle cottonseed oil.
75 % and 100 % solution of the test material in cottonseed oil were applied topically to the flank of one animal. 50 % and 25 % solution of the test material in cottonseed oil were applied topically to the flank of the second animal. 100 % of the test material as well as 100 % of cottonseed oil were applied topically to the flank of the third animal. The test material was kept under occlusive dressing for 6 hours. The degree of erythema or oedema was assessed according to Magnusson and Kligman scale at 24 and 48 hours after removal of the dressing. No signs of irritation were observed after application of 100 % concentration of the test material. 100 % concentration of the test material was chosen for the induction and challenge phases of the study.

MAIN STUDY
A. INDUCTION EXPOSURE
The left flank was cleared of hair by clipping.
Test group: a gauze patch was loaded with 0.5 ml of 100 % of the test material. The patch was held in contact with the skin under occlusive dressing for 6 hours. This procedure was repeated at the same test area at weekly intervals for 3 weeks.

Control group: Dry gauze patch was applied to the test area and kept under occlusive dressing for 6 hours. This procedure was repeated at the same test area at weekly intervals for 3 weeks.

B. CHALLENGE EXPOSURE
Both flanks were cleared of hair prior to application by clipping.
Test group: 14 days after the last induction, a patch of 100 % of the test material was applied to the skin of the right flank and held under occlusive dressing for 6 hours.
Control group: 14 days after the last induction, a dry patch was applied to the skin of the left flank and held under occlusive dressing for 6 hours
Challenge controls:
A dry patch was applied onto the skin of the negative control group.
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole 25 % in vasseline

Results and discussion

Positive control results:
At 24 hours 65 % of the positive control were sensitised and at 48 hours 55 % of them were still sensitised.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
other: challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
100% test substance
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: challenge. . Hours after challenge: 24.0. Group: test group. Dose level: 100% test substance. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Reading:
other: challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
100% test substance
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 100% test substance. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
other: challenge
Hours after challenge:
24
Group:
negative control
Dose level:
100% test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: challenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% test substance. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: challenge
Hours after challenge:
48
Group:
negative control
Dose level:
100% test substance
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: challenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 100% test substance. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Preliminary Irritancy Testing

1 animal was treated topically with concentrations of 100% (undiluted) and 75% of the test item (dissolved in cottonseed oil) for 6 hours. 1 animal was treated topically with concentrations of 50% and 25% of the test item (each dissolved in cottonseed oil) for 6 hours. 1 animal was treated topically with a concentration of 100% of the test item (undiluted) and with a concentration of 100% of cottonseed oil (undiluted) for 6 hours. Based on the results of this preliminary test, a concentration of 100% was selected for the inductions as well as for the challenge. This concentration did not cause any signs of irritation after a topical treatment over a period of 6 hours.

Main Test

Dermal Induction I, II and III (6·hour exposure, occlusive): Immediately after removing the patch: no signs of irritation were observed in any of the animals 24 hours after removing the patch: no signs of irritation were observed in any of the animals.

Challenge Exposure (6 hour exposure, occlusive):

The results of the test animals at the challenge phase were compared to the results of the control animals. Neither erythema nor oedema was observed in any animal at any time of observation. There was no evidence of sensitisation and the percentage of sensitised animals was 0%. The incidence index and severity index were 0. No signs of toxicity were recorded. Except one control animal, which was found dead on day 6 of the study, all animals survived during the observation period. At gross necropsy of this animal the stomach and small intestines were found to be bloody infiltrated. No other specific findings were noted. As this concerned a control animal and none of the other animals showed any clinical signs, this had no influence on the validity of the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The skin sensitisation study for 2,4-hexadienoic acid, 3-(trimethoxysilyl) propyl ester concluded that the test material was not sensitising to the skin.
Executive summary:

Test for Delayed-Type Hypersensitivity in Guinea Pigs (Closed Patch Test according to Buehler) with 2,4 -hexadienoic acid, 3-(trimethoxysilyl) propyl ester. The study was performed in order to assess the potential of 2,4 -hexadienoic acid, 3-(trimethoxysilyl) propyl ester to induce delayed type hypersensitivity when applied topically to albino guinea pigs (Crl: HA) following the OECD TG 406, EC 440/2008, OPPTS 870.2600 guidelines. Twenty (20) animals were used in the test group while 10 animals were allocated to the negative control group. Cottonseed oil was used as a vehicle (preliminary irritancy testing). The maximum concentration not giving rise to irritating effects in the preliminary test was 100%. Thus, the test material used at each stage of induction, as well as the challenge was applied at a 100% concentration (used as provided). The animals in the test group did not show any visible clinical symptoms during the study. No mortality occurred in the test group. One animal of the control group was found dead on day 6 of the study. No animals showed any skin reaction after 24 and 48 hour post challenge. No treatment related effects were observed in this study. In conclusion, under the conditions of the present study it can be stated that the test item 2,4 -hexadienoic acid, 3-(trimethoxysilyl) propyl ester caused no reactions identified as sensitisation at the tested concentration.