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Description of key information

The key skin sensitisation study for 3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate concluded that the substance was not sensitising to the skin. The study was conducted according to OECD TG 406 and in compliance with GLP (BSL Bioservice 2012d).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
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.
Species:
guinea pig
Strain:
other: Crl: HA
Sex:
female
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Remarks:
(Preliminary Irritancy Testing)
Concentration / amount:
Test animals:
Induction: 100 %
Challenge: 100 %

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

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.

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The key skin sensitisation study for 3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate concluded the substance was not sensitising to the skin. The study was conducted according to OECD TG 406 and in compliance with GLP (BSL Bioservice 2012d).

A 6 hour occlusive induction application, of the undiluted test material onto the right flank of 20 guinea-pigs resulted in no signs of erythema or oedema on any of the animals at 24 or 48 hours observations. Ten negative control guinea-pigs were also treated, with no evidence of erythema or oedema at 24 or 48 hours post-treatment.

Similarly, the 6 hour occlusive challenge application of the undiluted test material resulted in no erythema or oedema at the 24 or 48 hour post-treatment observation. Appropriate negative controls were in place, with no evident reactions.

An application of mercaptobenzothiazole 25% in vaseline was used for the positive control group, showing 65 % and 55 % sensitisation reaction at 24 and 48 hours post-treatment.

The current accepted and preferred method for skin sensitisation testing according to the REACH legislation (EC no 1907/2006) and CLP Regulation (EC No 1272/2008) is the murine local lymph node assay (LLNA). A validated test method, OECD TG 429 (OECD 2002) is available for the LLNA. The guideline acknowledges the limits of the LLNA, and states that there are instances where ‘test substance classes or substances containing functional groups shown to act as potential confounders’ make the use of guinea pig tests more appropriate. It is concluded that the LLNA is not applicable where the properties of the test material cause interference in the accuracy of the LLNA (OECD 2002). The statement in the OECD TG 429 is given with reference to the findings of Basketter et al. (2009a), who demonstrated false positives in silicon based substances which had previously been demonstrated to be non-sensitisers in the guinea pig maximisation test (GPMT). The importance of available evidence from guinea pig results, consideration of chemical reactivity, epidermal bioavailability and clinical and experimental human data are emphasised as central to reaching appropriate regulatory decisions for substances which have been shown to fall outside the specificity of the LLNA (Basketter et al., 2009b). The non-applicability of the LLNA for silicone based substances has also been demonstrated by Petry et al. (2012). The sensitisation potential of polyfunctional silicone materials was tested in a comparative study investigating the GPMT and the LLNA assays, which found the five tested substances to be negative in the GPMT whereas they were concluded to be weak to moderate skin sensitisers in the LLNA (Petry et al., 2012).

References:

Basketter D, Ball N, Cagen S, Carillo JC, Certa H, Eigler D, Garcia C, Esch H, Graham C, Haux C, Kreiling R, Mehling A (2009a). Application of weight of evidence approach to assessing discordant sensitisation datasets: implication for REACH. Reg. Toxicol. Pharmacol., 55, 90-96.

Basketter D, McFadden JF, Gerberick F, Cockshott A, Kimber I (2009b) Nothing is perfect, not even the local lymph node assay: a commentary and the implications for REACH.Contact Dermatitis, 60, 65-69.

Petry, T., Bosch, A., Coste, X., Dupuis, V., Eigler, D., Germain, P. (2012). An assessment of the skin sensitisation hazard of a group of polyfunctional silicones using a weight of evidence approach. Regulatory Toxicology and Pharmacology, 64, 305-314.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data for 3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate, no classification for skin sensitisation is required according to Regulation (EC) No. 1272/2008.