Butan-2-one O,O',O''-(vinylsilylidyne)trioxime

Endpoint summary

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

Reference

Reference 1

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 for cross-reference:

read-across source

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

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 chemical

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

Reading:

other: No details given

Group:

positive control

Remarks on result:

other: No details given

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.

Reference 2

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

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 chemical

Dose level:

50%

No. with + reactions:

14

Total no. in group:

15

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

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

Reading:

other: No details given

Group:

positive control

Remarks on result:

other: No details given

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).