Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20.04.2010 to 27.05.2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

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

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 B.V.
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 567-738 g
- Housing: Individually in Makrolon Type 4 cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Six days

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

IN-LIFE DATES: From: 20.04.2010 To: 27.05.2010

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Diglyme
Concentration / amount:
100% for induction and 1% for challenge
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Diglyme
Concentration / amount:
100% for induction and 1% for challenge
No. of animals per dose:
Three for irritation screen forinduction, challenge I and II, 10 for control group, 20 for test group.
Details on study design:
RANGE FINDING TESTS: The test item concentration used in the epidermal induction should be a concentration producing some irritation but not adversely affected the animals. During the irritation screen, the test item at 100% (as delivered) as well as the test item formulated at 75% and 50% in diglyme produced discrete/patchy erythema in most of the three irritation screen animals. A discrete/patchy erythema appeared only in one out of three animals after treatment with the test item at 25% in diglyme. Therefore, the test item concentration of 100% was considered to be suitable for the 3-week induction. The concentration used in the epidermal challenge was the maximum tested non-irritant concentration. In this study 1% was the highest tested non-irritant concentration suitable for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Three
- Exposure period: Six hours
- Test groups: 100 % test substance only
- Control group: Negative control of Diglyme
- Site: Left shoulder
- Frequency of applications: Every seven days (Test days 1, 8 and 15)
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Day 29
- Exposure period: Six hours
- Test groups: treated with 1% test substance
- Control group: treated with 1% test substance
- Site: Left posterior quadrant
- Concentrations: 1%
- Evaluation (hr after challenge): The grading method used for irritation screen, induction and challenge was identical. It was performed 24 ± 2 hours after removal of the patches for irritation screen, induction and challenge and repeated 24 ± 2 hours later (48-hour grades) for the irritation screen and the challenge.

OTHER: Viability/mortality was checked daily until termination of the test. Clinical signs and grading of skin response were recorded daily from delivery to termination of the test. Skin responses were graded during the irritation screens, induction and challenge periods. Body weights were recorded at delivery/acclimitisation start, at the end of the irritation screen, at test day 1 (day of treatment) and at the termination of the study.
Challenge controls:
Diglyme only
Positive control substance(s):
yes

Study design: in vivo (LLNA)

Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Descriptive statistics (means and standard deviations) were calculated for body weights. No inferential statistics were used.

Results and discussion

Positive control results:
Nine and six of twenty test animals were observed with discrete/patchy erythema at the 24- and 48-hour readings, respectively, after the challenge treatment with the highest tested non-irritating concentration of alph-hexylcinnamaldehyde at 5% in PEG 300. No skin effect was observed in the control group.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Diglyme only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Diglyme only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Diglyme only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Diglyme only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% . No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

Any other information on results incl. tables

There were no deaths or clinical signs of systemic toxicity in any animal. Body weights were unaffected by treatment.

In the test group treated with the test item at 100% (used as delivered), discrete/patchy erythema (grade 1) was observed in all 20 test animals during the first and second induction and in 3 out of 20 animals in the third induction. Discrete/patchy erythema (grade 1) was observed in one out of 10 control animals (10%) and in one out of 20 test animals (5%) after treatment with the test item at 1% in Diglyme. Therefore none of the reactions in the challenge phase were greater than those in the induction phase.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
In a skin sensitisation study (Buehler Test) conducted to OECD 406 and to GLP (reliability score 1) tris(2-methoxyethoxy)vinylsilane was not sensitising to the skin of guinea-pigs.