Butan-2-one O,O',O''-(methylsilylidyne)trioxime

Endpoint summary

Description of key information

Skin irritation / corrotion: Weight of evidence: Two studies are available. One was well conducted but non-standard  study (with GLP). The other was performed according to OECD 404.  Butan-2-one O,O',O''-(methylsilanetriyl)oxime was determined to be non-irritant to the skin of rabbits in both studies.

Eye irritation: Key study: Test method similar to OECD 405 and with GLP (RL2). Butan-2-one O,O',O''-(methylsilylidyne)trioxime was determined to be irritating to the eyes of 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:

weight of evidence

Study period:

02 Aug - 05 Aug 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

24 hour occlusive exposure

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Pine Acres Rabbitry, W. Brattleboro, VT
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: 2.2 - 2.6 kg
- Housing: single housing
- Diet: Charles River Rabbit Formula, Lot W1 3151; Agway Rabbit Prolab Formula, Lot W1 3189
- Water: tap water, ad libitum
- Acclimation period: at least 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 50±15
- Air changes (per hr): 12-16
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: control patches (+ve and -ve) are included on each animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

24 h

Observation period:

72 h
Reading time points: 1, 24, 48 h (after completion of exposure)

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: gauze patch sealed with plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: excess test substance was wiped
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

out of all 6 animals

Time point:

other: mean over 1, 24, 48 h, after completion of exposure

Score:

0.5

Max. score:

8

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test substance caused erythema (Grade 1) to 4 of 6 animals 1 h after removal of the patch. Erythema resolved at 3 sites by 24 h and at the remaining site by 48 h. Edema (Grade 1) was observed at the 4 sites displaying erythema at 1 h after patch removal. The edema had resolved at all 4 sites by 24 h. The Primary Dermal Irritation Index (mean of 1, 24, 48 h, following removal of the patch) was 0.5. The PDII for the negative control (untreated patch) was 0.0, and for the positive control (1% sodium lauryl sulphate) was 6.1.

Interpretation of results:

GHS criteria not met

Remarks:

CLP Implementation.

Conclusions:

A well reported, well conducted but non-standard study, with GLP, identified slight, transient effects to rabbit skin from 24-h occluded contact with the test material. The effects were fully reversible within 48 h, thus the test substance is considered not to be irritant to the skin.

Executive summary:

A skin irritation study was conducted with a method equivalent to OECD 404 according to GLP standards. Six New Zealand white rabbits were exposed to 0.5 mL test substance (undiluted) for 24 hours under a occlusive coverage. The observation period was 72 hours and reading time points at 1, 24 and 48 hours after completion of exposure. Positive and negative control patches were included on each animal. The reactions were scored according to Draize system. The test substance caused erythema (Grade 1) to 4 of 6 animals 1 h after removal of the patch. Erythema resolved at 3 sites by 24 h and at the remaining site by 48 h. Edema (Grade 1) was observed at the 4 sites displaying erythema at 1 h after patch removal. The edema had resolved at all 4 sites by 24 h. The Primary Dermal Irritation Index (mean of 1, 24, 48 h, following removal of the patch) was 0.5. The PDII for the negative control (untreated patch) was 0.0, and for the positive control (1% sodium lauryl sulphate) was 6.1. The substance was concluded to be non-irritating to the skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

19 Nov 1986 - 07 Jan 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The animals were observed for 72 hours only.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Observation period was too short (72 h) to evaluate the reversibility of effects. No data on substance purity were given.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, France
- Age at study initiation: No data
- Weight at study initiation: 2.5±0.2 kg
- Housing: Individual in polystyrene cages
- Diet: Rabbit complete pelleted maintenance food, ad libitum (UAR, formula 112, Epinay sur Orge, France)
- Water: Softened and filtered drinking water, ad libitum
- Acclimation period: Minimum of one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 19.11.1986 To: 22.11.1986

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

4 h

Observation period:

72 h
Reading time points: 1, 24, 48, 72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: Back and flanks
- % coverage: No data
- Type of wrap if used: Semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: yes, if any test substance was left on the skin
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Erythema (Grade 1) in 2 of 6 animals. No further observations of erythema.

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Erythema grade 1 were observed in 6/6 animals after 1 h, and were fully reversible within 48 h in 6/6 animals. No edema reactions were observed throughout the whole study period. Desquamation was still visible at 72 hours in 3 of 6 animals.

Interpretation of results:

not irritating

Remarks:

CLP Implementation.

Conclusions:

A reliable study conducted broadly in accordance with OECD 404 and GLP (reliability score 2) found the test material to be non-irritating to the skin of rabbits. Mild, transient erythema was replaced by desquamation that remained in some animals the end of the short observation period (72 h). There was no oedema evident at any time point.

Executive summary:

An skin irritation study was conducted according to OECD guideline 404 and GLP-standards. Six New Zealand white rabbits were exposed to the test substance for 24 hours under a semiocclusive coverage for 4 hours. Observations and readings according to the Draize system were performed at the following time points: 1, 24, 48 and 72 hours after the removal of the test substance. Erythema grade 1 were observed in 6/6 animals after 1 h, and were fully reversible within 48 h in 6/6 animals. No edema reactions were observed throughout the whole study period. Desquamation was still visible at 72 hours in 3 of 6 animals. Although desquamation remained in some animals after the short-observation period, the results indicate that the test substance does not have to be classified for skin irritation according to CLP Regulation (EC) 1272/2008.

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:

4 Aug 1983 - 11 Aug 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2002

Deviations:

yes

Remarks:

No sequential testing. Use of 9 animals (3 rinsed, 6 not rinsed).

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Pine Acres Rabbitry, Brattleboro, VT, USA
- Age at study initiation: 10-12 wk
- Weight at study initiation: 2.1-2.7 kg (based on age not weight)
- Housing: single housing
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: quarantine at least 2 wk, no further data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3
- Humidity (%): 50±15
- Air changes (per hr): 12-16
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1983-08-04 To: 1983-08-11

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye is generally used as the control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 ml
- Concentration: neat

Duration of treatment / exposure:

3 rabbits had the treated eye washed for 1 min after 20 secs. The remaining 6 were unwashed.

Observation period (in vivo):

7 days
Reading time points: 1, 24, 48, 72 h and daily until day 7

Number of animals or in vitro replicates:

9 (3 washed, 6 unwashed)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: the eyes of 3/9 were washed
- Time after start of exposure: 20 seconds

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0.16

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Corneal opacity, circumcorneal injection of the iris, conjunctival redness, chemosis, and discharge was observed in 5 of 6 unirrigated eyes within 24 hours of treatment. All irritation associated with exposure to the test substance was reversible within 7 days. Rinsing test eyes with tap water 20 seconds following instillation appeared to be beneficial in that it prevented positive ocular irritation in 2 of the 3 additional animals. For details see table 1.

Table 1: Irritant/corrosive response data for each animal at each observation time until effects no longer evident (observations continued to day 7)

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0/0/0/0/0/0	1/0/1/0/1/1	1/1/1/0/1/1	1/2/2/1/1/2
24 h	2/2/2/0/2/2	0/1/0/0/1/1	1/1/1/0/1/1	0/1/0/0/1/1
48 h	1/1/2/0/2/1	0/0/0/0/1/1	1/1/1/0/1/1	0/0/0/0/0/0
72 h	0/0/1/0/0/0	0/0/0/0/0/0	0/0/0/0/0/1	0/0/0/0/0/0
Average 24h, 48h, 72h	1	0.3	0.6	0.16
Reversibility*	c	c	c	c
Time for reversion	Day 4	72 h	Day 4	48 h

* Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

CLP Implentation.

Conclusions:

In a reliable eye irritation study, conducted in a manner similar to OECD 405 and with GLP (RL2) butan-2-one O,O',O''-(methylsilylidyne)trioxime was irritating to the eyes of rabbits based on 4/6 animals having a mean (24, 48 and 72 hour) score ≥1 for corneal effects.

Executive summary:

An eye irritation study was conducted with a method similar to OECD guideline 405 in accordance to GLP-standards. The undiluted test substance was applied to one eye of nine New Zealand white rabbits, the untreated eye served as control. Three rabbits had the treated eye washed for 1 min after 20 secs. The remaining six were unwashed. The eye reactions were scored according to Draize system at 1, 24, 48, 72 hours and daily up to day 7 after the substance application. Corneal opacity, circumcorneal injection of the iris, conjunctival redness, chemosis, and discharge was observed in 5 of 6 unirrigated eyes within 24 hours of treatment.  All irritation associated with exposure to the test substance was reversible within 7 days.  Rinsing test eyes with tap water 20 seconds following instillation appeared to be beneficial in that it prevented positive ocular irritation in 2 of the 3 additional animals. It was concluded that the test substance is irritating to the eyes based on 4/6 animals having mean (24,48,72h) score ≥ 1 for corneal effects.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / Corrosion:

Weight of evidence: A well reported, well conducted but non-standard study, with GLP, identified slight, transient effects to rabbit skin from 24-h occluded contact with the test material. The effects were fully reversible within 48 h, thus the test substance butan-2-one O,O',O''-(methylsilanetriyl)oxime is considered not to be irritant to the skin.

Weight of evidence: A reliable study conducted broadly in accordance with OECD 404 and GLP found the test material to be non-irritating to the skin of rabbits. Mild, transient erythema was replaced by desquamation that remained in some animals the end of the short observation period (72 h). There was no oedema evident at any time point. The substance butan-2-one O,O',O''-(methylsilanetriyl)oxime was determined to be non-irritant to the skin.

Eye irritation:

Key study: In a reliable eye irritation study, conducted in a manner similar to OECD 405 and with GLP. Butan-2-one O,O',O''-(methylsilanetriyl)oxime was irritating to the eyes of rabbits based on 4/6 animals having a mean (24, 48 and 72 hour) score ≥1 for corneal effects.

Justification for classification or non-classification

Skin irritation: Based on the available data, the substance is not classified as irritating according to CLP Regulation (EC) No 1272/2008.

Eye irritation: Based on the available data, the substance is classified as Irritating to eyes (category 2) according to CLP Regulation (EC) No 1272/2008 (cornea score >1 in 4/6 animals, reversible effects).