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

Endpoint summary

Description of key information

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

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
An in vitro study does not need to be conducted since adequate data from an in vivo skin sensitisation study are available.

Reference 2

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.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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)

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.

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)

Positive control results:

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

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

Negative control

Key result

Parameter:

SI

Value:

1.2

Test group / Remarks:

Low dose

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

Mid dose

Key result

Parameter:

SI

Value:

0.7

Test group / Remarks:

High dose

Key result

Parameter:

SI

Value:

10.2

Test group / Remarks:

Positive control

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

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 after3HTdR 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.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, the substance is not classified for skin sensitization according to CLP Regulation no. 1272/2008.