A mixture of: propan-2-one-O,O'(methoxyvinylsilandiyl)dioxime; propan-2-one-O-(dimethoxyvinylsilyl)oxime; propan-2-one-O,O',O''-(vinylsilantriyl)trioxime

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 12-19, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD Guideline 429, with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: propan-2-one-O,O'(methoxyvinylsilandiyl)dioxime; propan-2-one-O-(dimethoxyvinylsilyl)oxime; propan-2-one-O,O',O''-(vinylsilantriyl)trioxime

EC Number:

458-680-3

EC Name:

A mixture of: propan-2-one-O,O'(methoxyvinylsilandiyl)dioxime; propan-2-one-O-(dimethoxyvinylsilyl)oxime; propan-2-one-O,O',O''-(vinylsilantriyl)trioxime

Cas Number:

797751-44-1

Molecular formula:

not applicable, multiconstituent substance

IUPAC Name:

3-ethenyl-3-methoxy-6-methyl-2,4-dioxa-5-aza-3-silahept-5-ene; 5-ethenyl-2,8-dimethyl-5-{[(propan-2-ylidene)amino]oxy}-4,6-dioxa-3,7-diaza-5-silanona-2,7-diene; 5-ethenyl-5-methoxy-2,8-dimethyl-4,6-dioxa-3,7-diaza-5-silanona-2,7-diene

Test material form:

liquid

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelman
- Age at study initiation: 8 weeks
- Weight at study initiation: 16.8 – 20.1 g
- Housing: single caging. Makrolon cages type II
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8 ºC (average)
- Humidity (%): 48.2% (average)
- Photoperiod (hrs dark / hrs light): only artificial light from 6.00 a.m. to 6.00 p. m.

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

High dose: 100% test substance (as it is).
Mid dose: 50% (v/v) solution of the test substance in acetone:olive oil.
Low dose: 25% (v/v) solution of the test substance in acetone:olive oil.

No. of animals per dose:

five female mice/dose level.

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: Solubility testing showed that the test substance solves for at least 50% (v/v) in vehicle AOO.
- Irritation: about 24 hours after the last administration of the test substance as it is (100%) little increase in ear thickness was observed.

TREATMENT PREPARATION AND ADMINISTRATION:
Administration was performed epicutaneously to the dorsal surface of both ears, once a day on three consecutive days. The volume administered was 25 µL per ear.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The positive control result was: 42767 dpm (desintegrations per minute); and a SI (Stimulation Index) of 10.2

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

Negative control

Results 2

Key result

Parameter:

SI

Value:

1.2

Test group / Remarks:

Low dose

Results 3

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

Mid dose

Results 4

Key result

Parameter:

SI

Value:

0.7

Test group / Remarks:

High dose

Results 5

Key result

Parameter:

SI

Value:

10.2

Test group / Remarks:

Positive control

Any other information on results incl. tables

Body masses

The body mass of each animal was recorded on days 1 and 6.

Individual body masses (b.m.) and body mass gains in g of all animals. Means, standard deviations (SD) and number of animals per group (n).

group K negative control				group A (low dose)			group B (mid dose)				group C (high dose)				group P (positive control)
animal	b.m. on Day		b.m.	animal	b.m. on Day		b.m.	animal	b.m. on Day		b.m.	animal	b.m. on Day		b.m.	animal	b.m, on Day		b.m.
No.	1	6	gain	No.	1	6	gain	No.	1	6	gain	No.	1	6	oain	No.	1	6	gain
1	18.9	21,1	2.2	31	20.1	19.6	-0.5	36	18.8	20.7	1.9	41	17,7	19,2	1.5	21	18.3	19.0	0.7
2	18.7	20.3	1.6	32	18.1	19.4	1.3	37	18.0	18.6	0.6	42	20.0	20.5	0.5	22	19.9	21.3	1.4
3	19.4	20.0	0.6	33	19.2	20.1	0.9	38	18.8	20.4	1,6	43	16.8	17.8	1.0	23	17.3	18.9	1.6
4	17.8	17.8	0.0	34	18.5	20.1	1.6	39	18.6	19.9	1.3	44	18.6	19.7	1.1	24	18.0	18.9	0.9
5	19.7	21.3	1.6	35	19.5	20.2	0.7	40	19,3	21.2	1.9	45	19.7	21.8	2.1	25	19.3	19.8	0.5
mean	18.9	20.1	1.2	mean	19.1	19.9	0.8	mean	18.7	20.2	1.5	mean	18.6	19.8	1,2	mean	18.6	19.6	1.0
SD	0.7	1.4	0.9	SD	0.8	0.4	0.8	SD	0.5	1.0	0.5	SD	1.3	1.5	0.6	SD	1.0	1.0	0.5
n	5	5	5	n	5	5	5	n	5	5	5	n	5	5	5	n	5	5	5

Body masses and body mass gains of all animals were in the range to be expected from animals of the same strain, sex and age.

Body weight loss was noted in 1/5 animals in group A.

Evidence of sensitisation of each challenge concentration:

Results are presented as test/control ratio (Stimulation index), calculated as dpm test group/dpm negative control group, (dpm - disintegrations per minute, corrected by the subtraction of the background)

dpm results and calculated SIs

	dpm	SI
Group K (negative control)	4197	1
Group A (low dose)	4964	1.2
Group B (mid dose)	4383	1.0
Group C (high dose)	2736	0.7
Group P (positive control)	42767	10.2

SI: dpm test group/dpm negative contro) group

The stimulation indices of each of the 3 test substance concentrations were below 3: 1.2 at the low concentration, 1.0 at the mid concentration, and 0.7 at the high concentration.

theow concentration,  concentration The stimulation index of the positive control was 10.2.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified for skin sensitization (CLP Regulation EC no. 1272/2008)

Conclusions:

The test substance is regarded as a non sensitiser in the "Skin Sensitisation: Local Lymph Node Assay", since the SIs of all examined test substance concentrations were clearly smaller than 3.

Executive summary:

The "Skin Sensitisation: Local Lymph Node Assay" for the test substance was performed in five groups of 5 female CBA mice( According to OECD Guideline 429). The doses tested were 100% of test material (as it is); 50% (v/v) and 25 % (v/v). The vehicle used was acetone:oil (4:1, v/v) (AOO). A positive control (25% solution of hexyl cinnamic aldehyde in AOO) and a negative control (AOO) were included on the test. Both control substances were administrated under identical conditions as the test substance. The Administration was performed epicutaneously to the dorsal surface of both ears, once a day on three consecutive days. The volume administrated was 25 µl per ear. 5 days after the first topical administration, each animal received 20 µlCi3HTdR by intravenous administration. Approximately 5 hour after 3HTdR injection all animals were sacrificed and the3HTdR incorporation determinate. The application sites were visually checked for local irritations at least once a day. Body weight was recorded on days 1 and 6 after the administration.

The test substance is regarded as a not sensitising, since the SIs of all examined test substance concentrations were clearly smaller than 3.