A mixture of: propan-2-one-O,O'-(methoxymethylsilandiyl)dioxime; propan-2-one-O-(dimethoxymethylsilyl)oxime; propan-2-one-O,O',O''-(methylsilantriyl)trioxime

Endpoint summary

Description of key information

Skin irritation/corrosion: Key study: OECD Guideline 404 and GLP. The test item Wasox-MMAC2 did not show any skin irritation or corrosion in all treated NewZealand White rabbits.

Eye irritation: Key Study: OECD Guideline 405 and GLP. The test item Wasox-MMAC2 did not show any irritation to the eye in all treated New Zealand White rabbits.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 15-26, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD Guideline 404, with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 0-97633 Sulzfeld.
- Weight at study initiation: 1.8 – 2.1 kg
- Housing: Individual caging in metal wire cages, 79 cm x 59 cm bottom area, 38 cm height.
- Diet (e.g. ad libitum): ad libitum (Altromin 2123)
- Water (e.g. ad libitum): ad libitum (Tap water)
- Acclimation period: 5 days (animal nº 1) and 12 days (animals nº 2 and 3)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 19.2 ºC (continuous control and recording).
- Humidity (%): average of 50.1 ºC (continuous control and recording).
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: The surrounding of the administration area served as the untreated control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of the test substance
- Concentration (if solution): the test substance was used undiluted.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, and 72 hours after patch removal.

Number of animals:

3 female rabbits.

Details on study design:

TEST SITE
- Area of exposure: 2.5cm x 2.5cm
- Type of wrap if used: a semi-occlusive dressing
- Area of exposure: Median on the dorsal thoracal region.
- % coverage: 2.5 cm x 2.5 cm.
- Type of wrap if used: Samples were spread on cellulose patches and were held in place by fixing them marginally with non irritating tapes. The application sites were covered semiocclusively by a dressing. Access by the animals to the application sites was prevented by a plastic collar.

SCORING SYSTEM: According to guideline 404 (table: Grading of Skin Reactions)

Erythema / Eschar formation
0 No erythema.
1 Very slight erythema (barely perceptible).
2 Well-defined erythema.
3 Moderate to severe erythema.
4 Severe erythema (beet redness) or eschar formation (injuries in depth).

Oedema formation
0 No oedema.
1 Very slight oedema (barely perceptible).
2 Slight oedema (edges of area well defined by definite raising).
3 Moderate oedema (raised approximately 1 mm).
4 Severe oedema (raised more than 1 mm and extending beyond area of exposure).

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

All areas to be treated with the test substance and alt control areas were normal before the application and at each observation time.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Scores of the application sites:

Time after the end of the exposure	Erythema / Eschar animal Nos.			Oedema animal Nos.
	1	2	3	1	2	3
1 h	0	0	0	0	0	0
24 h	0	0	0	0	0	0
48 h	0	0	0	0	0	0
72 h	0	0	0	0	0	0
mean (24-72 h)	0.0	0.0	0.0	0.0	0.0	0.0

Scores of the application sites of animal No. 11 after exposure for 3 min, 1 h and 4 h:

Time after the end of the exposure	Erythema / Eschar Exposure Time			Oedema Exposure Time
	3 min	1 h	4 h	3 min	1 h	4 h
0 min	0	0	0	0	0	0

Interpretation of results:

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

Conclusions:

The acute dermal irritation/corrosion study in New Zealand White rabbits treated with a single administration of test article Wasox-MMAC2 (0.5 mL) did not show any sign of erythema/eschar or oedema during the test period and has to be considered "non irritant" for the skin.

Executive summary:

The Acute Dermal Irritation/Corrosion assay for the test substance Wasox-MMAC2 was performed in New Zealand White rabbits. 0.5 mL of the test material was applied to a site of 2.5cm x 2.5cm, of intact skin of 3 rabbits and covered by semi-occlusive dressing. The administration of the test substance was performed in a sequential manner. The first animal was exposed to the test substance stepwise at three sites of the skin: site 1 for three minutes, site 2 for 1 hour and site 3 for 4 hours. As no serious reactions were noted in the first animal, the remaining two animals were exposed to the test substance one week later for 4 hours. The treated areas of the animals were examined for erythema/eschar and oedema as well as other local skin alterations approximately at 1, 24, 48, and 72 hours after patch removal. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

The surrounding of the administration area, i.e. the untreated skin, served as a negative control. The treated areas of the animals did not show any sign of erythema/eschar and oedema during the test period and has to be considered "non irritant" for the skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 10-21, 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

According to OECD Guideline 405, with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633 Sulzfeld.
- Weight at study initiation: 2.0 – 2.6 kg
- Housing: Individual caging in metal wire cages, 79 cm x 59 cm bottom area, 38 cm height.
- Diet (e.g. ad libitum): ad libitum (Altromin 2123)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: 7 days (animal nº 41) and 14 days (animal nº 42 and nº 43)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 19.0 ºC (continuous control and recording).
- Humidity (%): average of 51.7% (continuous control and recording).
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of test substance
- Concentration (if solution): undiluted.

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

1, 24, 48 and 72 hours after the administration of the test substance

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
CORNEA
Opacity: degree of density (area most dense is taken for reading).
0 No ulceration or opacity.
1 Scattered or diffuse areas of opacity (except for slight dulling of normal lustre), details of iris clearly visible.
2 Easily discernible translucent area, details of iris slightly obscured.
3 Nacreous area, no details of iris visible, size of pupil barely discernible.
4 Opaque cornea, iris not discernible through the opacity.

IRIS
0 Normal.
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection; any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive).
2 No reaction to light, haemorrhage, gross destruction (any of all these or all together).

CONJUNCTIVAE
Redness: (refers to the most severe effect of palpebral and bulbar conjunctivae in comparison to the control eye).
0 Blood vessels normal.
1 Some blood vessels definitely hyperaemic (injected).
2 Diffuse crimson colour, individual vessels not easily discernible.
3 Diffuse beefy red.
Chemosis: lids and/or nictating membranes.
0 No swelling.
1 Any swelling above normal (includes nictating membranes).
2 Obvious swelling with partial eversion of lids.
3 Swelling with lids about half closed.
4 Swelling with lids more than half closed

TOOL USED TO ASSESS SCORE: otoscope lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

The untreated eyes (control eyes) were normal at each observation time.
The eyes, treated with the test substance (test eyes) were normal before the instillation and at each observation time.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Scores of the test eyes:

							Conjunctivae
Time after instillation (p.a.)	Corneae animal No.			Irises animal No.			Redness animal No.			Chemosis animal No.
	41	42	43	41	42	43	41	42	43	41	42	43
1 h	0	0	0	0	0	0	0	0	0	0	0	0
24 h	0	0	0	0	0	0	0	0	0	0	0	0
48 h	0	0	0	0	0	0	0	0	0	0	0	0
72 h	0	0	0	0	0	0	0	0	0	0	0	0
mean (24-72 h)	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

Interpretation of results:

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

Conclusions:

The acute eye irritation study in New Zealand White rabbits treated with a single administration of test article Wasox-MMAC2 (0.1 mL) has to be considered "non irritant" for the eye since no ocular lesions (cornea, irises, redness and chemosis) were observed during the 72 hours of exposure.

Executive summary:

The Acute Eye Irritation/Corrosion study for the test substance Wasox-MMAC2 was performed according to OECD Guideline 405 in New Zealand White rabbits. Firstly the test substance was administered to one animal. As there was no corrosive or severe irritant effect observed during the initial 72 h, the test substance was administered to two additional animals one week later. 0.1 mL of test item was instilled into the conjunctival sac of right eye of each of 3 rabbits (the left eyes remained untreated and served as a control). Both whole eyes of the animals were examined (especially the corneae, the irises and the conjunctivae) within 24 h before the instillation and approximately 1, 24, 48, and 72 hours after test substance administration. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. No ocular lesions (cornea, irises, redness and chemosis) were observed during the 72 hours of exposure. The substance has to be considered "non irritant" for the eye.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation 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 eye irritation study are available.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion: Key study: The Acute Dermal Irritation/Corrosion assay for the test substance was performed according to OECD Guideline 404 and GLP. Wasox-MMAC2 did not show any signs of erythema/eschar or oedema after single administration of the test substance (0.5 mL) in New Zealand White rabbits during 72 h of exposure and therefore, it has to be considered "non irritant" for the skin.

Eye irritation: Key study: The Acute Eye Irritation/Corrosion study for the test substance was performed according to OECD Guideline 405 and GLP. Wasox-MMAC2 did not show any ocular lesion (cornea, irises, redness or chemosis) after a single administration of the test substance (0.1 mL) in New Zealand White rabbits during 72 h of exposure, and therefore, it has to be considered "non irritant" for the eye

Justification for selection of skin irritation / corrosion endpoint:

Only one study available.

Justification for selection of eye irritation endpoint:

Only one study available.

Justification for classification or non-classification

Bases on the available information, the substance is not classified for irritation/corrosion according to CLP Regulation (EC) no. 1272/2008.