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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:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate test method.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test article ID (as cited in the study): Y-11870 is beta-(3,4-epoxycyclohexyl)ethyltriethoxysilane
Molecular formula: C13H26O4Si
Molecular weight: 274,43
Physical state: Clear, colorless liquid
Analytical purity: 92.7%
Lot/batch no: 113191
Source: CKWitco Corporation, Organosilicones Group, 3500 South State Route 2, Friendly, WV 26146
Test article receipt: 2000-06-19 (expiration date was not provided)
Stability under test conditions: Stable
Storage condition of test material: At room temperature; once opened, the test article was blanketed under nitrogen prior to being resealed
Certificate of analysis: see appendix IV (FTIR, GC/MS)

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: young adult
- Weight at study initiation: 292 to 335 grams (males) and 290 to 332 grams (females)
- Housing: Individual suspended wire mesh cages. The animals were maintained by the animal husbandry staff of WIL Research Laboratories, Inc. in accordance with standard operating procedures
- Diet: PMI Nutrition International, Inc Certified Guinea Pig LabDiet 5026 (analysis of feed was performed and provided by manufactureer)
- Water: municipal water were provided ad libitum (water was analyzed in accordance with standard operating procedures).
- Acclimation period: The animals used on the main study were acclimated to laboratory conditions for a minimum of seven days prior to initiation of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature: 68 to 74 °F
- Humidity (%): 30 to 62 %
- Photoperiod (12 hrs dark / 12 hrs light):

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
2.5%, 5%, 10%, 25%, 50%, 100% (primary irritation)
100% (induction)
100% (challenge)
50% (challenge; positive control)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol
Concentration / amount:
2.5%, 5%, 10%, 25%, 50%, 100% (primary irritation)
100% (induction)
100% (challenge)
50% (challenge; positive control)
No. of animals per dose:
test group: 10/sex
positive control: 5/sex
naive control: 5/sex
Details on study design:
Range finding test:
2.5, 5%, 10%, 25%, 50%, 100% (vehicle ethanol), 4/concentration
RANGE FINDING TESTS:
2.5, 5, 10, 25, 50, 100% (vehicle ethanol), 4/concentration

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 10 males, 10 females
- Control group: 5 males, 5 females (positive control); 5 males, 5 females (naive control)
- Frequency of applications: 7 days between application
- Concentrations: Test group 100% test substance; naive control untreated; positive control 100% hexylcinnamaldehyde HCH

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: challenge exposure 14 days following last induction
- Exposure period: 6 h
- Test groups: as above
- Control group: as above
- Concentrations: Test group 100% test substance; naive group 100% test substance; positive control 50% HCA in acetone
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
control group: 5/sex
Positive control substance(s):
yes
Remarks:
Hexylcinnamaldehyde (HCA)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
moderate to slight dermal reaction
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 12.0. Total no. in groups: 20.0. Clinical observations: moderate to slight dermal reaction.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
14
Total no. in group:
20
Clinical observations:
slight dermal reaction
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 14.0. Total no. in groups: 20.0. Clinical observations: slight dermal reaction.

Any other information on results incl. tables

                   Dermal Scores*    
 Group  Material  Interval  0  +/-  1  2  3  Sensitization Incidence Index  Severity Index
 test  100% TS  24 hours  0/20  8/20  11/20  1/20  0/20  70%  0.9
     48 hours  0/20  6/20  14/20  0/20  0/20    0.9
 naive control  TS  24 hours  1/10  9/10  0/10  0/10  0/10  not applicable  0.5
     48 hours  4/10  6/10  0/10  0/10  0/10    0.3
 positive control  HCA  24 hours  0/10  0/10  8/10  2/10  0/10  100%  1.2
     48 hours  0/10  0/10  9/10  1/10  0/10    1.1

*Skin reactions were graded:

0 no reaction

+/- slightly patchy erythema (equates to a score of 0.5)

1 slight confluent or moderately patch erythema

2 moderate erythema

3 severe erythema with or without edema

** Sensitization incidence index is the number of animals having post-challenge sensitization responses at either 24 or 48 hours divided by the number of animals in the group.

*** Severity Index: The Severity Index is the sum of the post-challenge test grades divided by the total number of animals tested (rounded to the nearest tenth). This index was calculated for each group separately at 24 and 48 hours. Grades of +/- were equal to 0.5 for calculation purposes.

There were no clinical findings noted during the study. There were no remarkable body weight changes observed during the study.

For the native control group, the test article produced nine very slight dermal reactions at the 24 hour observation and six very slight dermal reactions at the 48 hour observation. Reactions for the positive control group guinea pigs after challenge dosing included two moderate and eight slight dermal reactions at 24 hours post exposure. By 48 hours, dermal irritation included one moderate and nine slight reactions.

The test article produced one moderate (grade 2), 11 slight (grade 1) and eight very slight (grade +/-) dermal reactions for the test group guinea pigs at the 24 hours observation. At the 48 hour observation, 14 slight and six very slight dermal reactions were noted.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guinea pig sensitization test (Buehler method; non-adjuvant) reported that a 100% concentration of the test substance induced a sensitization response (in 70%) when challenged with a 100 % solution. Appropriate naive and positive complicance control were included.