Registration Dossier

Administrative data

Description of key information

Skin sensitisation: Key study: Based on the read-across approach from experimental data on analogue butan-2-one O,O',O''-(methylsilanetriyl)oxime (guinea-pig maximisation test, GLP study), the substance butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
The analogue Butan-2-one O,O',O''-(methylsilanetriyl)oxime which shares the same functional group with Butan-2-one O,O',O''-(vinylsilanetriyl)oxime, also has comparable values for the relevant molecular properties for skin sensitization.
See attached the reporting format.
Reason / purpose:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% (analogue substance)
No. with + reactions:
14
Total no. in group:
14
Remarks on result:
other: Read across from an analogue substance
Key result
Reading:
2nd reading
Hours after challenge:
28
Group:
test group
Dose level:
50% (analogue substance)
No. with + reactions:
14
Total no. in group:
15
Remarks on result:
other: Read across from an analogue substance
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% (analogue substance)
No. with + reactions:
1
Total no. in group:
3
Remarks on result:
other: Read across from an analogue substance
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% (analogue substance)
No. with + reactions:
0
Total no. in group:
3
Remarks on result:
other: Read across from an analogue substance
Interpretation of results:
other: Sensitising (according to CLP regulation)
Conclusions:
Based on the read-across approach from experimental results on analogue butan-2-one O,O',O''-(methylsilylidyne)trioxime, the read-across approach was applied and the substance butan-2-one O,O',O''-(vinylsilylidyne)trioxime was determined to be skin sensitiser.
Executive summary:

A guinea-pig maximisation test was conducted according to OECD 406 and GLP on the analogue substance butan-2-one O,O',O''-(methylsilylidyne)trioxime. 15 female guinea pigs were exposed to induction doses of 5% (intradermal) and 25% (epicutaneous) and a challenge dose of 50% test item. Another 3 females were used as negative controls. The results on the analogue reported a response to challenge in 14 of 15 animals at 24 and 48 h. Responses in 1 of 3 and 0 of 3 were reported at 24 and 48 hours, respectively, in the small negative control group. Based on these results, the read-across approach was applied and the substance butan-2-one O,O',O''-(vinylsilylidyne)trioxime was determined to be skin sensitiser since a response of 30% or more in an adjuvant test indicates sensitisation.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 Aug 1985 - 20 Nov 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The study was conducted according to a test protocol that is comparable to the appropriate OECD guideline, with acceptable restrictions. The restrictions were the use of less animals than specified in the OECD test guideline.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992
Deviations:
yes
Remarks:
Only 3 animals in the control group and 15 animals in the test group.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate guinea pig maximisation test is available which would not justify conducting an additional LLNA due to animal welfare.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazelton Labs, Denver, PA, USA
- Age at study initiation: 5-6 weeks
- Housing: up to 3 per cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±4
- Humidity (%): 50±15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1985-08-27 To: 1985-09-26
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Intradermal 5%; epicutaneous 25%
Route:
epicutaneous, semiocclusive
Vehicle:
propylene glycol
Concentration / amount:
50%
No. of animals per dose:
test: 15
negative control: 3 at challenge
Details on study design:
RANGE FINDING TESTS: said to have been conducted if necessary, but no details given in the report reviewed. The study schedule does not include a pretest, so it was probably not done.

A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections; 0.1 ml):
Injection 1: 5% test article in propylene glycol
Injection 2: FCA alone
Injection 3: 5% test article in FCA
Epicutaneous: 0.3 ml: 25% TS in propylene glycol
- Control groups:
Intradermal (3 pairs of injections; 0.1 ml):
Injection 1: vehicle
Injection 2: FCA alone
Injection 3: vehicle in FCA
Epicutaneous: 0.3 ml propylene glycol
- Site: two rows of 3 sites, one row either side of dorsal mid-line
- Frequency of applications: intradermal treatment day 0; topical induction day 7
- Duration: induction period continues to day 21
- Concentrations: intradermal 5%, epicutaneous 25%


B. CHALLENGE EXPOSURE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day of challenge: day 22
- Exposure period: 24h
- Test groups: 0.2 ml: 50% TS in propylene glycol
- Control groups: 0.2 ml: 50% TS in propylene glycol
- Site: flanks
- Concentrations: 50%


Challenge controls:
Negative: 6 animals were used at the induction stages. Only 3 were challenged with 50% TS. 3 animals were retained for a possible rechallenge.
Positive: dinitrochlorobenzene; no details are given
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene
Positive control results:
Dinitrochlorobenzene apparently yielded 100% response; no details are given.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
14
Total no. in group:
15
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
14
Total no. in group:
15
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
1
Total no. in group:
3
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
3

Table 1: Incidence of dermal response to challenge dosing.

GROUP

MATERIAL

INTERVAL

DERMAL SCORES

SENSITIZATION INCIDENCE

 

 

 

0

1

2

3

 

Test

TS 50%

24h

1/15

1/15

4/15

9/15

14/15

 

48h*

1/15

2/15

4/15

8/15

14/15

 

Vehicle (propylene glycol)

24h

0/15

0/15

0/15

0/15

0/15

 

48h

0/15

0/15

0/15

0/15

0/15

Vehicle control

TS 50%

24h**

2/3

1/3

0/3

0/3

1/3

 

48h

3/3

0/3

0/3

0/3

0/3

 

Vehicle (propylene glycol)

0/3

0/3

0/3

0/3

0/3

0/3

 

0/3

0/3

0/3

0/3

0/3

0/3

Positive control

Dinitrochlorobenzene (no details given)

 

 

 

 

 

100% no details given

Skin reactions were graded:

0 no reaction

1 scattered mild redness

2 moderate and diffuse redness

3 intense redness and swelling

* 5 animals had eschar and 2 had necrosis

**1 animal had eschar

Interpretation of results:
other: Sensitising (according to CLP regulation)
Conclusions:
A guinea-pig maximisation test conducted with GLP but limited in some respects reported a response to challenge (using 50% test substance) in 14 of 15 animals at 24 and 48 h. Responses in 1 of 3 and 0 of 3 were reported at 24 and 48 hours, respectively, in the small negative control group. A response of 30% or more in an adjuvant test indicates sensitisation.
Executive summary:

A guinea-pig maximisation test conducted with GLP but limited in some respects reported a response to challenge (using 50% test substance) in 14 of 15 animals at 24 and 48 h. Responses in 1 of 3 and 0 of 3 were reported at 24 and 48 hours, respectively, in the small negative control group. A response of 30% or more in an adjuvant test indicates sensitisation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Skin sensitisation: Read-across approach from analogue substance butan-2-one O,O',O''-(methylsilanetriyl)oxime

Key study: A guinea-pig maximisation test was conducted with GLP was performed on analogue substance butan-2-one O,O',O''-(methylsilanetriyl)oxime. The results reported a response to challenge (using 50% test substance) in 14 of 15 animals at 24 and 48 h. Responses in 1 of 3 and 0 of 3 were reported at 24 and 48 hours, respectively, in the small negative control group. A response of 30% or more in an adjuvant test indicates sensitisation. Based on this experimental data, a read-across approach was applied and the substance butan-2-one O,O',O''-(vinylsilanetriyl)oxime was determined to be skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available information, the test substance butan-2-one O,O',O''-(vinylsilanetriyl)oxime is classified as Sensitiser Category 1 according to CLP Regulation (EC) No 1272/2008 (>30 responding at >1% intradermal induction dose).