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

Skin sensitisation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

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:

The test was performed in 1985, i.e. before the entry into force of REACH Regulation.

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

245-366-4

EC Name:

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

Cas Number:

22984-54-9

Molecular formula:

C13H27N3O3Si

IUPAC Name:

butan-2-one O,O',O''-(methylsilanetriyl)oxime

Details on test material:

- Name of test material (as cited in study report): Tetra Oximino Silane

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: 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

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

propylene glycol

Concentration / amount:

Induction: intradermal 5%; epicutaneous 25%

Day(s)/duration:

single injection (intradermal) and 48h (epicutaneous)

Challenge

No.:

#1

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

Results and discussion

Positive control results:

Dinitrochlorobenzene apparently yielded 100% response; no details are given.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

14

Total no. in group:

15

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

14

Total no. in group:

15

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

50%

No. with + reactions:

1

Total no. in group:

3

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

50%

No. with + reactions:

0

Total no. in group:

3

Results 5

Reading:

other: No details given

Group:

positive control

Remarks on result:

other: No details given

Any other information on results incl. tables

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

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Remarks:

CLP Implementation.

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 was conducted in accordance to GLP-standards with a method similar to OECD guideline 406. Fifteen animals were initially (day 0) induced with a 5 % solution of test substance in propylene glycol injected by the intradermal route. A second induction (epicutaneous) was performed on day 7 with the test substance in propylene gylcol at 25 %, the exposure period was 48 hours. The induction period continued to day 21. On day 22 a semiocclusive epicutaneous induction was performed with the test substance in propylene glycol at 50 %. The challenge duration was 24 hours. The negative control group consisted of six animals at induction and three at challenge, three were retained for possible rechallenge. Positive control (dinitrochlorobenzene) was also included in the study design although no details are given.

The test substance caused signs of skin sensisisation in 14 /15 animals, based on the results, the substance was concluded to be a skin sensitizer and is classified in for this hazard in category 1B according to CLP Regulation.