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

Dermal irritation was scored according to OECD guideline nº 404. The treated areas of the animals did not show any sign of erythema/eschar and oedema.

Eye irritations were scored according to OECD guideline nº 405. No ocular lesions were observed at 72 hours.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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.

Reference 2

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
- Weight at study initiation: 1.8 – 2.0 kg
- Housing: Individual caging in metal wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days (animal nº 11) and 12 days (animals nº 12 and 13)

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

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes

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 (as it is)

Duration of treatment / exposure:

4 hours

Observation period:

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

Number of animals:

3 rabbits

Details on study design:

TEST SITE
- Area of exposure: 2.5cm x 2.5cm
- Type of wrap if used: a semi-occlusive dressing

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

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

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

Other effects:

No relevant findings.

Scores of the application sites

                 Individual data and means

Time after the end of the exposure	Erythema / Eschar animal Nos.			Oedema animal Nos.
	11	12	13	11	12	13
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 as skin irritant (CLP Regulation EC no. 1272/2008)

Conclusions:

The treated areas of the animals did not show any sign of erythema/eschar and oedema as well as other local skin alterations.

Executive summary:

The Acute Dermal Irritation/Corrosion assay for the test substance 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.

The surrounding of the administration area, i.e. the untreated skin, served as a negative control. Dermal alterations were scored according to OECD guideline nº 404.

The treated areas of the animals did not show any sign of erythema/eschar and oedema.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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.

Reference 2

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:

guideline study

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
- Weight at study initiation: 2.2 – 2.3 kg
- Housing: Individual caging in metal wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days (animal nº 51) and 14 days (animal nº 52 and nº 53)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 19.0 ºC
- Humidity (%): average of 51.7%
- 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:

0.1 mL of test substance

Duration of treatment / exposure:

72 hours (the treated eyes were not washed)

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: eye irritations were scored according to guideline 405

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: animals were examined using and otoscope lamp

Irritation parameter:

cornea opacity score

Remarks:

Opacity(degree of density)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: mean scores of animals 51, 52, and 53

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: mean scores of animals 51, 52, and 53

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: 51

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: mean

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: 52

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: mean

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: 53

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: mean

Irritation parameter:

chemosis score

Remarks:

lids and/or nictating membranes

Basis:

animal: 51

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Remarks:

lids and/or nictating membranes

Basis:

animal: 52

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Remarks:

lids and/or nictating membranes

Basis:

animal: 53

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: mean

Irritant / corrosive response data:

Reversibility of any observed effect: all changes observed were fully reversible within 3 days
After the instillation of the test substance the following findings were made:
- Corneae and irises were not affected.
- Conjunctivae, redness (a score 1) was noted in all animals from 24 h after application (p.a.) onwards until a maximum of 48 h p.a.
- Conjunctivae, chemosis (a score 1) was observed in 2/3 animals only 1 h (p.a.). A scored of 3, later on decreasing to 1, was noted in 1/3 animals from 1h p.a. onwards until 48 h p.a.

Other effects:

Ocular discharge was noted in 2/3 animals from 1h onwards until a maximum of 24 h after test substance application.

Scores of the test eyes:

   Examination of corneae, irises and conjunctivae. Individual data and means.*
               

							Conjunctivae
Time after instillation (p.a.)	Corneae animal No.			Irises animal No.			Redness animal No.			Chemosis animal No.
	51	52	53	51	52	53	51	52	53	51	52	53
1 h	0	0	0	0	0	0	0	0^2)	0^3)	1	1	3
24 h	0	0	0	0	0	0	1	1	1^2)	0	0	2
48 h	0	0	0	0	0	0	0	0	1	0	0	1
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	0.3	0.3	0.7	0.0	0.0	1.0

²⁾ Discharge with moistening of the lids and hairs just adjacent to the lids.

³⁾ Discharge with moistening of the lids and considerable area around the eye.

*Dermal alterations were scored according to OECD guideline nº 405.

Interpretation of results:

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

Conclusions:

No ocular lesions were observed at 72 hours.

Executive summary:

The Acute Eye Irritation/Corrosion study for the test substance was performed in New Zealand White rabbits. 0.1 mL of the test material was administrated per animal into the conjunctival sacs of the right eyes. The eyes were held closed for about one second to prevent loss of the test substance. The left eyes remained untreated and served as a control. The administration of the test substance was performed in a sequential manner. The first animal was exposed to the test substance, as no evidence for serious damage to the eye of the animal was found during the initial 72 h observation period, the test substance was administrated to the others two animals. 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. Eye irritations were scored according to OECD guideline nº 405.

No ocular lesions were observed at 72 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The Acute Dermal Irritation/Corrosion assay for the test substance 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.

The surrounding of the administration area, i.e. the untreated skin, served as a negative control.

The Acute Eye Irritation/Corrosion study for the test substance was performed in New Zealand White rabbits. 0.1 mL of the test material was administrated per animal into the conjunctival sacs of the right eyes. The eyes were held closed for about one second to prevent loss of the test substance.The left eyes remained untreated and served as a control. The administration of the test substance was performed in a sequential manner. The first animal was exposed to the test substance, as no evidence for serious damage to the eye of the animal was found during the initial 72 h observation period, the test substance was administrated to the others two animals. 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.

Justification for classification or non-classification

Based on the available information, the test item is neither classified as skin corrosion/irritation nor as serious eye damage/eye irritation in accordance with CLP Regulation (EU) No. 1272/2008.