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Skin sensitisation

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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to current OECD guideline and in compliance with GLP and considered reliability 1. Read-across is considered scientifically valid and reliability 2.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
Trimethoxyvinylsilane
EC Number:
220-449-8
EC Name:
Trimethoxyvinylsilane
Cas Number:
2768-02-7
IUPAC Name:
trimethoxy(vinyl)silane

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: mineral oil
Concentration / amount:
This study consisted of three phases. The Primary Irritation Phase consisted of an intradermal and a topical range-finding study. The intradermal range-finding study evaluated the irritation potential of A-171 in mineral oil and in a 1:1 Freund's Complete Adjuvant (FCA) and sterile saline mixture. The topical range-finding study was used to evaluate the irritation threshold concentration of A-171 following a single topical application. The definitive study consisted of the Induction Phase and the Challenge Phase.

Primary Irritation Phase: The Primary Irritation Phase utilized 28 guinea pigs. In the intradermal range finding study, two male and two female Hartley albino guinea pigs each received six 0.1 mL intradermal injections on the dorsal surface along the spine. The animals received injections of A-171 at 1%, 3%, or 5% in mineral oil or 1:1 FCA:sterile saline. In the topical range-finding study, 12 male and 12 female Hartley albino guinea pigs were each
exposed at 0.3 mL/site to five concentrations of A-171 in acetone (2.5%, to 50%), to nine concentrations of A-171 in mineral oil (0.5% tor 75%), or to undiluted A 171 or 100% mineral oil. There were three sites per guinea pig and four sites per concentration. The treatment was applied beneath a Hill Top Chamber® and held in place for six hours. The chambers were occluded with plastic wrap and overwrapped with Elastoplast tape. The treated sites were examined approximately 24 and 48 hours after the end of exposure. Based on the results, the concentrations chosen for intradermal induction dosing were 3% in 1:1 FCA:saline and 5% in mineral oil, and the concentration chosen for topical induction dosing was 5% in mineral oil. The highest non-irritating concentration, 5% in mineral oil, was chosen for challenge dosing.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
This study consisted of three phases. The Primary Irritation Phase consisted of an intradermal and a topical range-finding study. The intradermal range-finding study evaluated the irritation potential of A-171 in mineral oil and in a 1:1 Freund's Complete Adjuvant (FCA) and sterile saline mixture. The topical range-finding study was used to evaluate the irritation threshold concentration of A-171 following a single topical application. The definitive study consisted of the Induction Phase and the Challenge Phase.

Primary Irritation Phase: The Primary Irritation Phase utilized 28 guinea pigs. In the intradermal range finding study, two male and two female Hartley albino guinea pigs each received six 0.1 mL intradermal injections on the dorsal surface along the spine. The animals received injections of A-171 at 1%, 3%, or 5% in mineral oil or 1:1 FCA:sterile saline. In the topical range-finding study, 12 male and 12 female Hartley albino guinea pigs were each
exposed at 0.3 mL/site to five concentrations of A-171 in acetone (2.5%, to 50%), to nine concentrations of A-171 in mineral oil (0.5% tor 75%), or to undiluted A 171 or 100% mineral oil. There were three sites per guinea pig and four sites per concentration. The treatment was applied beneath a Hill Top Chamber® and held in place for six hours. The chambers were occluded with plastic wrap and overwrapped with Elastoplast tape. The treated sites were examined approximately 24 and 48 hours after the end of exposure. Based on the results, the concentrations chosen for intradermal induction dosing were 3% in 1:1 FCA:saline and 5% in mineral oil, and the concentration chosen for topical induction dosing was 5% in mineral oil. The highest non-irritating concentration, 5% in mineral oil, was chosen for challenge dosing.
No. of animals per dose:
Definitive study:
10/sex/dose with test material
5/sex/dose with Positive Control
5/sex/dose with Negative Control
Details on study design:
On study day 0, a group of 10 male and 10 female Hartley albino guinea pigs was dosed intradermally (0.1 mL/site) with duplicate injections of a 1:1 mixture of FCA and sterile saline, a 5% w/v mixture of A-171 in mineral oil, and a 3% w/v mixture of A-171 in 1:1 FCA:saline. On study day 6, the application site of all animals was pretreated with 0.5 mL of 10% sodium lauryl sulfate (SLS). On study day 7, the test group was topically induced with 5%
A-171 in mineral oil (approximately 0.4 to 0.5 mL) using the procedure described above. The duration of exposure was forty-eight hours. Two weeks after the topical induction exposure, the animals were challenge dosed for detection of sensitization by topical application of 5% A-171 at 0.3 mL/site to previously unexposed areas of skin. The guinea pigs were observed twice daily for mortality for the duration of all phases of the study. All sites were depilated and graded at 24-hours and 48-hours using the 0-to-3 grading scale. The initial and final body weights of the animals were recorded. Grades of 1 or greater in the test group would indicate sensitization, provided grades of less than 1 are seen in the vehicle control animals. Body weights and clinical observations were recorded on the day before initiation of dosing and at termination.
Challenge controls:
A positive control group of 5 male and 5 female guinea pigs was induced and challenged with -Hexylcinnamaldehyde (HCA; a known sensitizer). A naïve control group of 5 male and 5 female guinea pigs was dosed only at challenge with 5% A-171 in mineral oil at 0.3 mL/site and served as an irritation control.
Positive control substance(s):
yes
Remarks:
Hexylcinnamaldehyde

Results and discussion

Positive control results:
9/10 and 4/10 animals showed positive reactions at the 24 and 48 hour observations, respectively.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5% A-171 in mineral oil
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
5 slight (grade 1) reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% A-171 in mineral oil. No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: 5 slight (grade 1) reactions.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% A-171 in mineral oil
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% A-171 in mineral oil. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5% A-171 in mineral oil
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
4 slight (grade 1) reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5% A-171 in mineral oil. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: 4 slight (grade 1) reactions.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
5% A-171 in mineral oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5% A-171 in mineral oil. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1% HCA in acetone
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
One moderate (grade 2) and 8 (grade 1) slight reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 1% HCA in acetone. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: One moderate (grade 2) and 8 (grade 1) slight reactions.
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
1% HCA in acetone
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
4 slight (grade 1) responses
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 1% HCA in acetone. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: 4 slight (grade 1) responses.

Any other information on results incl. tables

One Negative Control Group-I male died on study day 9.  This death was considered a spontaneous occurrence and was replaced with a Negative 

Control Group-II male.  There were no clinical findings or remarkable body weight changes noted during the study. 

The Sensitization Incidence Index for the test group was calculated to be 0% (0/20) following challenge.  The Irritation Severity Index was 0.3 and 0.0 at the 24- and 48-hour evaluation, respectively, for the Test Group.  The
Irritation Severity Index for the Negative Control Group was 0.4 and 0.0 at the 24- and 48-hour evaluations,
respectively.  The Sensitization Incidence Index was calculated to be 90% (9/10) for the Positive Control Group
following challenge dosing with 1.0% HCA in acetone.  The Irritation Severity Indices were 1.0 and 0.4 at 24 and 48
hours, respectively, for the Positive Control Group.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, A-171 did not elicit a delayed contact hypersensitivity response in guinea pigs.