Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
OECD 406 (Buehler test) commissioned
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP and is considered to be reliability 1. Read-across is considered to be scientifically valid and reliability 2.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,1,3,3-Tetramethyl-1,3-divinyldisilazane

- Physical state: colourless liquid

- Storage condition of test material: Room temperature, protect against moisture. Keep container tightly closed and store in a cool well ventilated place. Store under nitrogen.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan laboratories, The Netherlands
- Age at study initiation: 4-6 weeks
- Weight at study initiation: test group: 373.1-408 g
- Housing: in groups of up to ten in stainless steel cages with standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: diglyme, 75% w/w mixture
Concentration / amount:
INDUCTION: 25% w/w
CHALLENGE: 0.1% w/w and 0.5% w/w
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: diglyme, 75% w/w mixture
Concentration / amount:
INDUCTION: 25% w/w
CHALLENGE: 0.1% w/w and 0.5% w/w
No. of animals per dose:
Pretests: 3
Controls: 10
Test group: 20
Details on study design:
RANGE FINDING TESTS: Pretest 1 was performed during the acclimatization of the main study animals. The test item concentrations were selected during the preliminary solubility testing. The test item was formulated in the vehicle. Pretests 2 and 3 were performed during the induction period in order to find the highest non-irritant test item concentration for the challenge.

MAIN STUDY
A. INDUCTION EXPOSURE

The induction of the main test was performed within three weeks. A total of three inductions (one per week) was performed. The test item concentration used for the induction was determined based on the results of pretest 1. A test item concentration of 25% (w/w) in diglyme was well tolerated systemically and caused mild-to-moderate skin irritation.

The application was performed at the same shoulder of the animals in the first and in the second week of the induction period. As crusts were observed after the second induction in the test group, a naive application site on the right shoulder was used for the third induction for both test and control group. After the last induction exposure, the animals were left untreated for approximately 2 weeks before the challenge.


B. CHALLENGE EXPOSURE

The challenge was performed ca. 2 weeks after the last induction. The test item concentration used for the challenge was determined based on the results of the pretests. All concentrations higher than 0.5% (w/w) tested in the pretests produced in signs of skin irritation. Test item concentrations of 0.5% (w/w) and 0.1% (w/w) in diglyme were well tolerated systemically and 0.5% (w/w) in diglyme was the highest non-irritant concentration.
Challenge controls:
No skin reactions were observed.
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamaldehyde

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: induction
Group:
test group
Dose level:
25% (w/w) in diglyme
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
Discrete or patchy erythema in all animals.
Remarks on result:
other: Reading:
Reading:
other: induction
Group:
negative control
Dose level:
Diglyme
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions.
Remarks on result:
other: Reading:
Reading:
other: challenge
Group:
test group
Dose level:
0.1%, 0.5% (w/w) in diglyme.
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No skin reactions.
Remarks on result:
other: Reading:
Reading:
other: challenge
Group:
negative control
Dose level:
0.1%, 0.5% (w/w) in diglyme.
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions.
Remarks on result:
other: Reading:

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
Based on a non-adjuvant sensitisation test in guinea pigs conducted according to an OECD guideline and in compliance with GLP, the test item was found not sensitising to guinea-pig skin, in accordance with current regulation (EC 1272/2008).