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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
from 8 Jan 1997 to 10 Feb 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(though not explicitly stated)
Deviations:
no
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Buehler test method. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Test material

Constituent 1
Chemical structure
Reference substance name:
3-aminopropyltriethoxysilane
EC Number:
213-048-4
EC Name:
3-aminopropyltriethoxysilane
Cas Number:
919-30-2
Molecular formula:
C9H23NO3Si
IUPAC Name:
3-triethoxysilylpropan-1-amine

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elm Hill Breeding Labs (no further information)
- Age at study initiation: 4 wk
- Weight at study initiation: 293-400 g
- Housing: 1/wire mesh cage
- Diet: standard dient ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26 (the guideline recommends 20 +/- 3)
- Humidity (%): 40-70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1997-01-08 To: 1997-02-10

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
peanut oil
Concentration / amount:
induction: 20%
challenge: 5%
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
peanut oil
Concentration / amount:
induction: 20%
challenge: 5%
No. of animals per dose:
test group: 10/sex
negative control: 5/sex
positive control: 3/sex
Details on study design:
RANGE FINDING TESTS:
1st: 40, 60, 80 and 100% (vehicle peanut oil), 4/concentration
2nd: 5, 10, 20 and 30% (vehicle peanut oil), 4/concentration

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 10 males, 10 females
- Control groups: vehicle: 5 males, 5 females; positive: 3 males, 3 females
- Frequency of applications: 7-days between applications
- Concentrations: test groups 20% TS in peanut oil; positive control 0.3% DNCB in 80% ethanol

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 groups: as above
- Site: test group TS 5% left flank; vehicle control group TS 5% left flank, vehicle right flank; positive control group DNCB 0.02% left flank, 0.2% right flank
- Concentrations: test group 5% TS in peanut oil; vehicle control 5% TS in peanut oil; positive control 0.02 and 0.2% DNCB in acetone
- Evaluation (hr after challenge): 24 and 48 h
Challenge controls:
vehicle control group: 5/sex
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene (DNCB)

Results and discussion

Positive control results:
See table 1. The sensitization incidence index of 100% from tests with the know n sensitizer DNCB at 0.2% confirms the validity of the test method.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
slight erythema
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
slight or moderate erythema
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.2 % DNCB
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.2 % DNCB
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.02 % DNCB
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.02 % DNCB
No. with + reactions:
1
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Peanut oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Peanut oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Table 1: Incidence of dermal response to challenge dosing

GROUP

MATERIAL

INTERVAL

DERMAL SCORES*

SENSITIZATION INCIDENCE INDEX**

SEVERITY INDEX***

0

±

1

2

3

Test

TS 5%

24h

14/20

3/20

3/20

0/20

0/20

3/20

0.2

48h

4/20

9/20

3/20

4/20

0/20

7/20

0.8

Positive control

DNCB 0.2%

24h

0/6

0/6

1/6

3/6

2/6

6/6

2.2

48h

0/6

0/6

1/6

3/6

2/6

6/6

2.2

DNCB 0.02%

24h

2/6

4/6

0/6

0/0

0/0

0/6

0.3

48h

0/6

5/6

1/6

0/0

0/0

1/6

0.6

Vehicle control

TS 5%

24h

9/10

1/10

0/10

0/10

0/10

0/10

0.1

48h

7/10

2/10

1/10

0/10

0/10

1/10

0.2

Peanut oil

24h

10/10

0/10

0/10

0/10

0/10

0/10

0

48h

10/10

0/10

0/10

0/10

0/10

0/10

0

*Skin reactions were graded:

0 no reaction or very slight dispersed redness. No swelling.

± slight patchy erythema (equates to a score of 0.5)

1 slight confluent or moderately patchy erythema

2 moderate erythema

3 severe erythema with or without oedema

** Sensitization incidence index: number of animals with dermal scores greater than those of the negative control group at 24h or 48h, divided by the number of animals tested. Grades of 1 or greater are considered indicative of sensitization in the positive control group

*** Severity index: the sum of test grades divided by the number of animals tested (given for 24h and 48h observations separately)

(From SIAR, 2003)

There were no signs of systemic toxicity during the study. All animals gained weight during the study and there was no significant test -article related differences in vehicle and test group mean body weight.

No positive responses were observed in the peanut oil control animals at either the vehicle or test article sites at the 24-hour grading. In the peanut oil control animals at the 48-hour grading one animal exhibited a positive response at the test article site, a grade of one (1). Of the twenty animals induced with the test article at 20% and challenged at 5%, three animals were observed with a positive response of one (1) at the 24-hour grading, and three exhibited a positive response of one (1) and four exhibited a positive response of two (2) at the 48 hour grading. The positive control animals induced and challenged with DNCB exhibited the anticipated responses at challenge, indicating a reliable and valid test.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
A well conducted, well-documented guinea-pig skin sensitization test (Buehler method) reported that a 20% concentration of the test material in peanut oil induced a sensitization response (in 35%) when challenged with a 5% solution. Appropriate concurrent negative and positive compliance controls were included.

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