2-butanone-O,O',O''-(phenylsilylidyne)trioxime

Endpoint summary

Description of key information

Skin irritation: Key study: Test method EEC B4, OECD 404. GLP study. According to CLP Regulation, the test substance is not classifed as irritating to the skin.
Eye irritation: Key study: Test method EEC B5, OECD 405. GLP study. According to CLP Regulation, the test substance is not classfied as irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-03-02 to 1999-03-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test method according to EEC method B4, OECD guideline 404 with GLP.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Ltd, Margate, Kent, England.
- Age at study initiation: at least 14 weeks of age
- Weight at study initiation: 2.9 to 3.4 kg
- Housing: Individually in stainless steel cages with perforated floors.
- Diet: ad libitum
- Water: ad libitum
-Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS:
-Temperature: 19 to 20°C
- Humidity: 35 to 48%
- Photoperiod: 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 h

Observation period:

Examination of the treated skin was made on Day 1, 2, 3 and 4. Additional observations were made for two animals on Days 5 through 10.

Number of animals:

3

Details on study design:

TEST SITE
-Area of exposure: 25 mm x 25 mm of dorso-lumbar region
-Type of wrap if used: gauze pad under "Elastoplast" elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE:
- Washing (if done): Yes, washed with warm water (36ºC) and blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

SCORING SYSTEM: According to guidelines
ERYTHEMA AND ESCHAR FORMATION
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) or eschar formation (injuries in depth) preventing erythema reading: 4

OEDEMA FORMATION
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (edges raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: Mean 24-72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: Mean 24-72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: Mean 24-72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: Mean 24-72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: Mean 24-72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: Mean 24-72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Slight to well-defined dermal initation (erythema with oedema up to Grade 2) was seen in two animals following removal of the dressings and over the following days, resolving completely by Day 10. In addition, desquamation of the stratum corneum (characterised by dryness and sloughmg) was observed in one of these rabbits. No dermal initation was observed in the remaining rabbit throughout the study.

Dermal reactions:

Rabbit	E= Erythema O= Oedema	Day										Mean 24-72h
		1*	2	3	4	5	6	7	8	9	10
1933 Male	E	1	1	1	1	2	2	1	1	1	0	1.0
	O	1	1	0	0	0	0	0	0	0	0	0.3
	Other	-	-	A	a	a	a	a	a	a	-	-
1934 Male	E	1	2	2	2	2	2	1	1	1	0	2.0
	O	1	2	2	0	0	0	0	0	0	0	1.3
	Other	-	-	A	a	a	a, b	a, b	a, b	a, b	b	-
1935 Male	E	0	0	0	0	-	-	-	-	-	-	0.0
	O	0	0	0	0	-	-	-	-	-	-	0.0
	Other	-	-	-	-	-	-	-	-	-	-	-

*: Approximately 30 minutes after removal of the dressing

a: Patchy response

b: Desquamation of the stratum comeurn (characterised by dryness and sloughing)

-: Not applicable

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to CLP Regulation, the test item is not classified as irritating to the skin.

Executive summary:

A skin irritation study was performed with test item in accordance with EEC Method B4 and OECD Guideline 404. Three rabbits were each administered a single dermal dose of 0.5 ml of the test substance (as received) for four hours under semi-occlusive conditions and observed for up to ten days. Slight to well-defined dermal initation (erythema with oedema up to Grade 2) was seen in two animals following removal of the dressings and over the following days, resolving completely by Day 10. The mean 24 -72 hours erythema scores were 1.0, 2.0 and 0.0 and the mean 24 -72 oedmea scores 0.3, 1.3 and 0.0 for each animal respectively. In addition, desquamation of the stratum corneum (characterised by dryness and sloughmg) was observed in one of these rabbits. No dermal initation was observed in the remaining rabbit throughout the study. According to CLP Regulation, the test item is not classified as irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-02-10 to 2000-02-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Test method according to with EEC method B5, OECD guidelin 405 with GLP.

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Initial weight: 2.1 to 3.2 kg
- Age at test initiation: At least 10 weeks of age
- Housing: Individually in metal cages with perforated floors.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 21 days

ENVIRONMENTAL CONDITIONS:
-Temperature: 23 to 24°C
- Humidity: <20 to 35%
- Photoperiod: 12 hours of artificial light (0600 - 1800 hours GMT) in each 24 hours period.

In-life dates: from: Feb 10, 2000; To: Feb 14, 2000.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 ml of the test substance placed in the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing.

Duration of treatment / exposure:

Single exposure.

Observation period (in vivo):

1 hour and 1, 2 and 3 days after instillation. Additional observations were made for one animal four days after instillation.

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: According to guidelines.
CORNEAL OPACITY: Degree of density (area most dense taken for reading)
- No ulceration or opacity: 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible: 1
- Easily discernible translucent area, details of iris slightly obscured: 2
- Nacreous area, no details of iris visible, size of pupil barely discernible: 3
- Opaque cornea, iris not discernible through the opacity: 4

IRIS:
- Normal: 0
- 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): 1
- No reaction to light, haemorrhage, gross destruction (any or all of these): 2

CONJUNCTIVAE: Redness (refers to palpebral and bulbar conjunctivae)
- Blood vessels normal: 0
- Some blood vessels definitely hyperaemic (injected): 1
- Diffuse, crimson colour, individual vessels not easily discernible: 2
- Diffuse beefy red: 3

EDEMA: Lids and/or nictitating membranes
- No swelling: 0
- Slight swelling (includes nictitating membranes): 1
- Obvious swelling with partial eversion of lids: 2
- Swelling with lids about half-closed: 3
- Swelling with lids more than half-closed: 4

TOOL USED TO ASSESS SCORE: handheld light

OTHER OBSERVATIONS: Clinical signes: All animals were observed daily for signs of ill health or toxicity.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24-72h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 3 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean 24-72h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 3 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean 24-72h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean 24-72h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean 24-72h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean 24-72h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean 24-72h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean 24-72h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean 24-72h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean 24-72h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean 24-72h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean 24-72h

Score:

0

Max. score:

2

Irritant / corrosive response data:

Dulling of the cornea was evident one hour after dosing only in one of the three treated animals No iridial inflammation was observed in any animal throughout the observation period. Conjunctival inflammation up to Grade 2 in intensity was evident in all three animals one hour after instillation, with the level of response decreasing over the following days before resolving in all instances between three and four days of instillation.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Oculat reactions:

Rabbit	Region of the eye		One hour	Day after installation
				1	2	3	4
100 Female	Cornea	Density	D	0	0	0	0
		Area	4	0	0	0	0
	Iris		0	0	0	0	0
	Conjunctiva	Redness	2	2	1	1	0
		Chemosis	2	0	0	0	0
95 Female	Cornea	Density	0	0	0	0	-
		Area	0	0	0	0	-
	Iris		0	0	0	0	-
	Conjunctiva	Redness	2	1	1	0	-
		Chemosis	2	0	0	0	-
96 Female	Cornea	Density	0	0	0	0	-
		Area	0	0	0	0	-
	Iris		0	0	0	0	-
	Conjunctiva	Redness	2	1	1	0	-
		Chemosis	2	0	0	0	-

D: Dulling of the cornea

-: Not applicable

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In accordance with CLP Regulation, the test substance is not classified as irritating to the eyes.

Executive summary:

An eye irritation study was performed with thest item according to EEC Method B5 and OECD Guideline 405. Three rabbits were each administered a single ocular dose of a volume of 0.1 ml of the test substance and observed for up to four days after instillation. Test item elicited dulling of the cornea (evident one hour after dosing only in one of the three treated animals), no iridial inflammation and transient conjunctival inflammation up to Grade 2 in intensity evident in all three animals one hour after instillation, with the level of response decreasing over the following days before resolving in all instances between three and four days of instillation. The mean 24 -72 hours conjunctivae redness scores were 0.7, 0.7 and 1.3 for each animal. On the basis of these results and in accordance with CLP Regulation, the substance is not classified as irritating to the eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation:

Key study: A skin irritation study was performed with test item in accordance with EEC Method B4 and OECD Guideline 404. Three rabbits were each administered a single dermal dose of 0.5 ml of the test substance (as received) for four hours under semi-occlusive conditions and observed for up to ten days. The mean 24 -72 hours erythema scores were 1.0, 2.0 and 0.0 and the mean 24 -72 oedmea scores 0.3, 1.3 and 0.0 for each animal respectively. The observed effects were completely resolved by Day 10. According to CLP Regulation, the test item is not classified as irritating to the skin.

Supporting study: The potential irritation effects of test item were evaluated on the skin of New Zealand White rabbits. Each of three rabbits received three 0.5 mL doses of the test article and one 0.5 mL dose of the positive control article (1 % sodium lauryl sulfate). The doses of the test article were held in contact with the skin under an occlusive binder for exposure periods of 3 minutes, 1 hour and 4 hours. The positive control article was dosed in the same manner for an exposure period of 4 hours. The test sites were subsequently examined and scored for dermal irritation for up to 9 days following patch removal. The mean 24 -72 hours erythema and oedema scores for sites with 4 hours exposure period were as follows: 1.3, 1.6 and 2 (erythema); 0.6, 0.6 and 2 (oedema) for each animal respectively. The observed effects were resolved completely by study day 8. Based on these results and according to CLP Regulation, the test substance is not classfied as irritating to the skin.

Eye irritation:

Key study: An eye irritation study was performed with thest item according to EEC Method B5 and OECD Guideline 405. Three rabbits were each administered a single ocular dose of a volume of 0.1 ml of the test substance and observed for up to four days after instillation. The mean 24 -72 hours conjunctivae redness scores were 0.7, 0.7 and 1.3 for each animal. The effects were fully reversible by Day 4. Non effects were seen for chemosis, cornea and iris. On the basis of these results and in accordance with CLP Regulation, the substance is not classified as irritating to the eyes.

Supporting study: The potential irritant effects of test item were evaluated on the eyes of New Zealand White rabbits. Each of three rabbits received a 0.1 mL dose of the test article in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 7 days following dosing. The mean 24 -72 hours scores were determined for each animal as follows: Cornea: Opacity: 0, 0, 0.3 and Area: 0, 0.6, 0.3; Iris: 0.3, 0.3, 0.3; Conjunctivae: Redness: 1.3, 1, 2; Swelling: 1.3, 1, 1; Discharge: 0, 0, 0.6. All the effects were reversible by the end of the observation period except conjunctival irritation (slighe erythema) which persisted in Day 7. According to the author, this was not considered as a possitive effect. Based on this data and according to CLP Regulation, the test substance is not classified as irritating to the eyes.

Justification for selection of skin irritation / corrosion endpoint:
The key study with Klimisch score = 1 is selected.

Justification for selection of eye irritation endpoint:
The key study with Klimisch score = 1 is selected.

Justification for classification or non-classification

Skin irritation: Based on the available data (24 -72h mean value of erythema and oedema <2.3, effects fully reversible), the test substance is not classifies as irritating to the skin in accordance with CLP Regulation (EC) no. 1272/2008.

Eye irritation: Based on the available data (24 -72h mean value of corneal opacity <1, iritis <1, conjunctival redness <2 and conjunctival oedema <2, effects fully reversible), the test substance is not classified as irritating to the eyes in accordance with CLP Regulation (EC) no. 1272/2008.