Registration Dossier

Administrative data

Description of key information

In a test for delayed-type hypersenitivity in guinea pigs (closed patch test according to Buehler) conducted according to OECD Guidelines 406, EU Method EC 440/2008 and EPA OPPTS 870.2600 and in accordance with the Principles of GLP, groups of guinea pigs were exposed dermally to HES10108 (Supplied as DOW CORNING® BY 16-122 B).

 

Under the conditions of the present study it can be stated that the test item HES10108 (Supplied as DOW CORNING® BY 16-122 B) caused no reactions identified as sensitisation at the tested concentration.

 

According to Commission Regulation (EU) No 286/2011 as well as OECD-GHS (Globally Harmonized Classification System) the test item HES10108 (Supplied as DOW CORNING® BY 16-122 B) has no obligatory labelling requirement for skin sensitisation and is unclassified.

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:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
There were no deviations from the study plan
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The closed patch test for delayed-type hypersensitivity is performed on the guinea pig. It has been the animal of choice for predictive sensitisation tests for several decades. The assessment of the test item to produce skin sensitisation is achieved through multiple exposures under standardised conditions. Animals of either sex are acceptable for use according to DECO 406.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
HES10108 (supplied as Dow Corning BY 16-122B
- Expiration date of the lot/batch:
25-August-2017 / Lot number 0008624816
- Purity test date:
-14-April-2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
0°C -32 °C, protected from light. Do not store with strong
oxidising agents
- Stability under test conditions:
the liquid test item was tested undiluted
- Solubility and stability of the test substance in the solvent/vehicle:
not applicable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:
not applicable

Other
- Physical state - liquid
- Color - colorless
- Active components - 95%: 3-Methacryloxypropyltris {[tris(trimethylsiloxy) silyl]
ethyldimethylsiloxy} silane
- Purity - 99.3% (non-volatile content)
Species:
guinea pig
Strain:
other: Crl: HA - Guinea Pigs (full barrier)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 4 weeks old
- Weight at study initiation: 329-360 g
- Housing: The animals were kept in groups in Terluran - cages on Altromin saw fibre
bedding
- Diet (e.g. ad libitum): Free access to autoclaved hay and to Altromin 3122 maintenance diet for guinea pigs, rich in crude fibre
- Water (e.g. ad libitum): Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: Adequate acclimatisation period (at lp.aRt fivp. clays)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 ml
Day(s)/duration:
once a week at the same test srea at weekly intervals for 3 weeks
Adequacy of induction:
not specified
No.:
#20
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 ml of the test substance
Day(s)/duration:
14 days after the last induction, dermal application for 6 hours
Adequacy of challenge:
not specified
No. of animals per dose:
Number of animals in the preliminary test: 2
Number of animals in the test group: 20
Number of animals in the negative-control group: 10
Details on study design:
RANGE FINDING TESTS: Before the initiation of the preliminary test, a solubility test was performed to define the maximum concentration which is technically applicable to the animals. Solubility was found for the vehicle acetone at a concentration of 75%.
Two different concentrations of the test item (100%, undiluted and 75%, diluted with the vehicle acetone) were applied topically to the flanks of the animals for 6 hours using occlusive dressings to determine the concentrations for the main study.
2 animals were treated topically with a concentration of 100% of the undiluted test item on the left flank and with a concentration of 75% of the test item (dissolved in acetone, Sigma, lot no. MKBN6172V, expiry date: 01/2017) on the right flank for 6 hours. A Hill Top Chamber® was loaded with 0.5 mL of the prepared test substance. The chamber was applied to the test area of approximately 2.5 x 2.5 cm and was held in contact with the help of an occlusive dressing. Based on the results of this preliminary test the following concentrations were chosen for the main test:
a concentration of 100% for the dermal inductions
a concentration of 100% for the challenge application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours/day - once a day/week for 3 consecutive weeks
- Test groups: 20 animals
- Control group: 10 animals
- Site: The left flank was cleared of hair (close-clipped) prior to the first application and again prior to further applications during Induction I, 2 and 3
- Frequency of applications: This procedure was repeated once a week at the same test area at weekly intervals for 3 weeks.
- Duration: 6 hours/day - once a day/week for 3 consecutive weeks
- Concentrations: 0.5 ml of undiluted test substance

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after last induction
- Exposure period: 6 hours under occlusive conditions
- Test groups: 20 animals
- Control group: 10 animals
- Site: both flanks were cleared of hair (close-clipped) prior to challenge application
- Concentrations: 0.5 ml of undiluted test substance
- Evaluation (hr after challenge): approximately 21 hours after removing the Hill Top Chamber, the challenge area was cleaned and cleared of hair by the use of depilatory cream. Approximately 24 and 48 hours after removing the patch the skin reaction was observed and scored accordingly
Challenge controls:
Test Group and Negative Control Group:
Both flanks were cleared of hair (close-clipped) prior to the challenge application. 14 days after the last induction application 0.5 mL of the test substance were loaded on a Hill Top Chamber®, applied to an area of approximately 2.5 x 2.5 cm on the right flank and held in contact with the help of an occlusive dressing for 6 hours. A dry Hill Top Chamber® was applied to an area of approximately 2.5 x 2.5 cm on the left flank at an untreated site (intraspecific control) and was held in contact with the help of an occlusive dressing for 6 hours
Positive control substance(s):
yes
Remarks:
Positive-Control Substance: mercaptobenzothiazole, purity> 98%, Aldrich, lot no.: BCBC5206V, expiry date: 03/2019
Positive control results:
The sensitisation rate after application of the positive-control substance mercaptobenzothiazole (25% in vaseline) was 85%, confirming the reliability of the test
system.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
All animals of both groups survived throughout the test period. No signs of toxicity were recorded .Neither erythema nor oedema was observed in any animal at any time of observation.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
same as above
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
same as above
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
same as above
Remarks on result:
no indication of skin sensitisation

All animals of both groups survived throughout the test period. No signs of toxicity were recorded .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%.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study it can be stated that the test item HES10108 (Supplied as DOW CORNING® BY 16-122 B) caused no reactions identified as sensitisation at the tested concentration.
According to Commission Regulation (EU) No 286/2011 as well as OECD-GHS (Globally Harmonized Classification System) the test item HES10108 (Supplied as DOW CORNING® BY 16-122 B) has no obligatory labelling requirement for skin sensitisation and is unclassified.
Executive summary:

In a test for delayed-type hypersenitivity in guinea pigs (closed patch test according to Buehler) conducted according to OECD Guidelines 406, EU Method EC 440/2008 and EPA OPPTS 870.2600 and in accordance with the Principles of GLP, groups of guinea pigs were exposed dermally to HES10108 (Supplied as DOW CORNING® BY 16-122 B).

Under the conditions of the present study it can be stated that the test item HES10108 (Supplied as DOW CORNING® BY 16-122 B) caused no reactions identified as sensitisation at the tested concentration.

According to Commission Regulation (EU) No 286/2011 as well as OECD-GHS (Globally Harmonized Classification System) the test item HES10108 (Supplied as DOW CORNING® BY 16-122 B) has no obligatory labelling requirement for skin sensitisation and is unclassified.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a test for delayed-type hypersenitivity in guinea pigs (closed patch test according to Buehler) conducted according to OECD Guidelines 406, EU Method EC 440/2008 and EPA OPPTS 870.2600 and in accordance with the Principles of GLP, groups of guinea pigs were exposed dermally to HES10108 (Supplied as DOW CORNING® BY 16-122 B). Under the conditions of the present study it can be stated that the test item HES10108 (Supplied as DOW CORNING® BY 16-122 B) caused no reactions identified as sensitisation at the tested concentration. According to Commission Regulation (EU) No 286/2011 as well as OECD-GHS (Globally Harmonized Classification System) the test item HES10108 (Supplied as DOW CORNING® BY 16-122 B) has no obligatory labelling requirement for skin sensitisation and is unclassified.