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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:
16 February 2016 to 12 May 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 0008356364; no data on source
- Expiration date of the lot/batch: 04.06.2016
- Purity test date: 02.05.2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, keep away from oxidizing agents, use with adequate ventilation, avoid moisture and repeated exposure to air
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: The test substance was soluble in DMSO and Acetone. 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 %.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For the challenge 0.15 ml of the test item was dissolved with the vehicle to give a final volume of 20 ml. The solution was prepared directly before application.
- Final dilution of a dissolved solid, stock liquid or gel: not applicable
- Final preparation of a solid: not applicable

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Crl: HA
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Females: not applicable
- Microbiological status of animals, when known: no data
- Age at study initiation: 4 weeks old
- Weight at study initiation: 344 - 401 g
- Housing: housed in a semi barrier in an air-conditioned room
- Diet: autoclaved hay and Altromin 3122 maintenance diet for guinea pigs, rich in crude fibre, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: none

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 10 x/ hour
- Photoperiod (hrs dark / hrs light): 12/ 12

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other: Acetone
Concentration / amount:
100 %
Day(s)/duration:
Once a week for 6 hours for 3 weeks
Adequacy of induction:
highest technically applicable concentration used
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Acetone
Concentration / amount:
0.75 %
Day(s)/duration:
single 6-hour application
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Preliminary test: 5
Test group: 20
Negative control group: 10
Details on study design:
RANGE FINDING TESTS: Different concentrations of the test sample diluted with the vehicle acetone were applied topically to the flanks of 5 animals for 6 hours using occlusive dressing to determine the concentrations for the main study. The first animal was treated with 100% (undiluted), 75%, 1.5% and 0.75% of the test item in acetone; the second animal was treated with 50% and 25%; the third animal was treated with 12.5% and 6.25%; the fourth animal was treated with 6.25% and 3% and the fifth animal was treated with 1.5% and 0.75%.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three topical induction exposures
- Exposure period: one a week for 6 hours for 3 weeks
- Test groups: a Hill Top Chamber loaded with 0.5 ml of the test substance
- Control group: an empty Hill Top Chamber
- Site: left flank (2.5 x 2.5 cm)
- Frequency of applications: single 6-hour application, once a week for 3 weeks
- Duration: 6 hours
- Concentrations: 100 %

B. CHALLENGE EXPOSURE
- No. of exposures: single exposure
- Day(s) of challenge: 14 days after the last induction application
- Exposure period: 6 hours
- Test groups: a Hill Top Chamber loaded with 0.5 ml of the test substance (right flank) and a Hill Top Chamber loaded with 0.5 ml of the vehicle (left flanks)
- Control group: a Hill Top Chamber loaded with 0.5 ml of the test substance (right flank) and a Hill Top Chamber loaded with 0.5 ml of the vehicle (left flanks)
- Site: right and left flanks of both test and negative control groups
- Concentrations: 0.75 %
- Evaluation (hr after challenge): at 24 and 48 hours after removing the patch the skin reactions were evaluated

Challenge controls:
Intraspecific control: the left flank (untreated site) of all the animals was treated with 0.5 ml of acetone
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole, 50 % in vaseline at inductions I, II and III, and 25 % in vaseline at challenge

Results and discussion

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.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.75 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Neither erythema nor oedema was observed in any of the animals; no signs of toxicity were recorded; all animals survived throughout the test period
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.75%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Neither erythema nor oedema was observed in any of the animals; no signs of toxicity were recorded; all animals survived throughout the test period
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Neither erythema nor oedema was observed in any of the animals; no signs of toxicity were recorded; all animals survived throughout the test period
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.75%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Neither erythema nor oedema was observed in any of the animals; no signs of toxicity were recorded; all animals survived throughout the test period
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50% mercaptobenzothiazole (in vaseline) inductions I, II and III; 25% (in vaseline) challenge.
No. with + reactions:
17
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
The recent reliability check was performed in Novenber/December 2015; the results are expresses as percentage of animals with reactions. The number of animals in the group was not stated but has been assumed to be 20.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50% mercaptobenzothiazole (in vaseline) inductions I, II and III; 25% (in vaseline) challenge.
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Remarks:
The recent reliability check was performed in Novenber/December 2015; the results are expresses as percentage of animals with reactions. The number of animals in the group was not stated but has been assumed to be 20.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The skin sensitisation study, conducted according to OECD TG 406 and in compliance with GLP, reports the test substance, 1, 1, 1, 3, 5, 5, 5-heptamethyl-3-octyltrisiloxane, to be not sensitising to the skin of guinea pigs.