Registration Dossier

Administrative data

Description of key information

Skin sensitisation (OECD 406, guinea pig): not sensitising

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:
03 Aug - 21 Oct 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
(2003)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Schwabach, Germany
Type of study:
Buehler test
Justification for non-LLNA method:
In a recent study by Petry et al. (unpublished) the applicability of the in vitro direct peptide reactivity assay (DPRA), the KeratinoSens™ and the human cell line activation test (h-CLAT) and in the modified myeloid U937 skin sensitization test (mMUSST) has been determined for eight members of the heterogeneous group of silicone-based substances for which in vivo data was already available. Therein, the data presented provide insights into technical challenges encountered and limitations when testing such type of polysiloxanes and silanes for skin sensitization in currently proposed in vitro models and allow only a preliminary evaluation of current proposals for the hazard assessment and classification of chemical substances for the skin sensitization endpoint solely on the basis of in vitro data. The applicability is further limited by the hydrolytic instability of the test item as well as the fact that silanol hydrolysis products can form condensation products of even lower water solubility.
It is therefore concluded that, at present, the available in vitro test methods are not suitable to correctly predict the skin sensitising potential of these types of polysiloxanes and silanes and that future work has to focus on improving the understanding of the mode of action how such materials cause skin sensitisation and identifying most suitable in vitro skin sensitisation testing strategies accordingly.
The Buehler type of sensitization test was selected since the test substance is a functional silane and the Local Lymph Node Assay as the preferred alternative has shown to provide false positive results for silicone substances.

Literature
Petry, T., Bosch, A., Coste, X., Eigler, D., Germain, P., Seidel, S. and Jean, P. A. Evaluation of in vitro assays for the assessment of the skin sensitization hazard of functional polysiloxanes and silanes (unpublished)
Species:
guinea pig
Strain:
other: Crl:HA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approximately 4 weeks
- Weight at study initiation: 300 - 334 g
- Housing: animals were kept in groups in Terluran cages on Altrumin saw fibre bedding
- Diet: autoclaved hay and Altromin 3122 maintenance diet for guinea pigs, rich in crude fibre, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Concentration / amount:
100%
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Concentration / amount:
50%
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
4 (preliminary test), 20 (test group), 10 (control group)
Details on study design:
RANGE FINDING TESTS
Two animals were treated topically with concentrations of 100% and 75% of the test item (suspended in cottonseed oil) for 6 h. Two additional animals were treated topically with concentrations of 50% and 25% of the test item (suspended in cottonseed oil) for 6 h. Based on the result of the preliminary test, a concentration of 100% was selected for the dermal inductions. The concentration caused slight signs of irritation without leading to systemic effects. A concentration of 50% was found to be the highest dose which did not cause any signs of irritation after a topical treatment over a period of 6 h and therefore was chosen for the challenge application in the main test.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in cottonseed oil
- Control group: cottonseed oil
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-21
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: Day 28
- Exposure period: 6 h
- Test groups: test substance in cottonseed oil
- Control group: test substance in cottonseed oil and cottonseed oil only
- Site: right flank (test substance), left flank (cottonseed oil)
- Concentrations: 50%
- Evaluation (hr after challenge): 24 and 48 h after patch removal
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole (induction: 50% in vaseline; challenge: 25% in vaseline)
Positive control results:
The sensitisation rate after application of the positive control substance mercaptobenzothiazole (Induction: 50% in vaseline; Challenge: 25% in vaseline) was 95% (19/20 animals with erythema, grade 1 after 24 h and 13/20 animals with erythema, grade 1 after 48 h) confirming the reliability of the test system. The recent reliability check was performed in May/June 2015.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs observed
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no clinical signs observed
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs observed
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitising properties of the registered substance triethoxyhexadecylsilane (CAS 16415-13-7) were tested in a study according to OECD TG 406 under GLP conditions using the test for delayed contact hypersensitivity in guinea pigs (Buehler test, BSL, 2016). The test for delayed contact hypersensitivity was performed on 30 female Cr.: HA guinea pigs. For the dermal inductions the initially test item concentration was 100% (v/v). A 50% (v/v) preparation of the test item was selected for the challenge application. Topical application of the appropriate test substance concentration (20 test animals) or vehicle (10 control animals) was performed once a week for 6 hours at the left flanks of each animal for three consecutive weeks. Seven days following the last topical application of the test substance or vehicle (cotton seed oil) all animals were challenged with the test substance at a concentration of 50% (v/v) for 6 hours. Skin reactions of all animals were evaluated 24 and 48 hours after challenge administration. No skin reactions were noted after challenge administration. Periodic reliability checks with the positive control (Mercaptobenzothiazole) gave the expected results. Thus, triethoxyhexadecylsilane (CAS 16415-13-7) was not skin sensitising under the conditions of this Buehler test.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation of the registered substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.