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 acute oral median lethal dose (LD50) of test substance is higher than 2000 mg/kg body weight in rats.

Also the LD50 dermal of the test substance was higher than 2000 mg/kg body weight in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From september 28, 2004 to october 13, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD 423 Guideline , with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 180 - 199 g
- Fasting period before study: the food was withdrawn the evening before the administration of the test substance
- Housing: single caging in Makrolon cages type III
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22 ºC
- Humidity (%): average 56.1%
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: the test substance was not soluble in water. Corn oil is a common vehicle for acute oral toxicity testing

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: From comparable chemical substances, a minor acute toxicity is known; therefore it seemed appropriate to perform the limit test with the dose 2000 mg per kg body weight.

Doses:

2000 mg/kg body weight.

No. of animals per sex per dose:

3 females per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before the test and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

dissolved

Mortality:

No mortality occurred.

Clinical signs:

other: 1/6 animals was affected. The finding, observed only 0.5 hours after the administration, was signs of reduced well-being.

Gross pathology:

Effects on organs: No relevant findings at post mortem examination were noted.

Synopsis of the results:

Table1:    

Dose	Step No.	Animal	Number of animals
(mg/kg)		Nos.	exposed	affected	deceased
2000	1	51, 52, 53	3	1	0
2000	2	54, 55, 56	3	0	0

Body weights and body weight gain:

Table2: Individual data, means and standard deviations SD.

Dose	Animal	Body weight (g)				Body weight gain (g)
mg/kg (Step No.)	No.	before administr.	7 days p.a.	14 days p.a.	death	0-7 days p.a.	7-14 days p.a.
2000	51	199	211	230	-	12	19
(1)	52	186	204	223	-	18	19
	53	181	209	224	-	28	15
	mean	188.7	208.0	225.7	-	19.3	17.7
	SD	9.3	3.6	3.8	-	8.1	2.3
2000	54	189	206	229	-	17	23
(2)	55	180	200	218	-	20	18
	56	186	202	212	-	16	10
	mean	185.0	202.7	219.7	-	17.7	17.0
	SD	4.6	3.1	8.6	-	2.1	6.6

Observations in life:

Table3:     A grade of severity was recorded where applicable (low - mid - high)

Findings	Dose (mg/kg), Step No.	No. of the affected animals	Observation time (p.a.) first    last	Maximum grade of severity
signs of reduced well-being	2000, 1	51	0.5 h	-
normal at any time	2000, 1	52, 53	0 h / 14 d	-
	2000, 2	54, 55, 56	0 h / 14 d	-

1/6 animals was affected. The finding, observed only 0.5 h after the administration, was: Signs of reduced well-being.
This term encompasses unspecific alterations, like sedation, apathy, piloerection, hunched posture or closed eyes, in single or multiple occurrence.

Interpretation of results:

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

Conclusions:

The LD50, oral of the test substance is higher than 2000 mg/kg body weight in rats.

Executive summary:

The Acute Toxic Class Method assay (Limit Test) for the test substance was performed in rats (According to OECD 423 Guideline). Two groups of three fasted female was treated sequentially with a single oral dose of 2000 mg/kg bodyweight. The test material was administrated orally as an emulsion in corn oil.

Clinical sign and body weight were monitored during the study. All animals were subjected to gross necropsy (no relevant findings at post mortem examination were noted).

The acute oral median lethal dose (LD50) of test substance is higher than 2000 mg/kg body weight in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII, Column 2, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely. In case of the product the exposure by inhalation during manufacturing of the product as well as during its use for the sealant production and use by the customer is unlikely.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 13 - October 12, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD 402 Guideline, with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga
- Age at study initiation: approximately 8 weeks (males) and 12 weeks (females)
- Weight at study initiation: 245-254g (males) and 229-240 g (females)
- Housing: single caging in Makrolon cages type III
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average 22 ºC
- Humidity (%): average 56%
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: an area of 6.5 cm x 8 cm (52 cm2) on the dorsal thoracal region
- % coverage: at least 10% of the estimated body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): if necessary, residual test substance was wiped off using cellulose tissue
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg per kg body weight

Duration of exposure:

24 hours

Doses:

One dose level of 2000 mg/kg body weight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed 0 - 0.5, > 0.5 - 1, > 1 - 2, > 2 - 4 and > 4 - 6 hours after administration of the test substance and then at least once a day for a total of 2 weeks. Body weights were determinate before administration, 7 and 14 days after administration.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: No relevant findings in life were noted, except for signs of discomfort in 1 male rat a day after the test substance administration. The clinical signs were chromodacryorrhoea, attributed to the discomfort caused by the dressing and was not considered to

Gross pathology:

Effect on organs: no relevant findings were noted.

Other findings:

No relevant local findings were noted.

Body weights and body weight gain:

 

Individual data, mean and standard deviation SD

Sex	No.	before administr.	7 days p.a.	14 days p.a.	death	0-7 days p.a.	7-14 days p.a.
	11	253	276	320	-	23	44
2000 mg/kg	12	251	298	351	-	47	53
male	13	245	278	322	-	33	44
	14	246	268	311	-	22	43
	15	254	284	332	-	30	48
	mean	250	281	327	-	31.0	46.4
	SD	4	11	15	-	10.1	4.2
	16	239	244	263	-	5	19
2000 mg/kg	17	236	241	263	-	5	22
female	18	240	249	266	-	9	17
	19	234	241	257	-	7	16
	20	229	232	254	-	3	22
	mean	236	241	261	-	5.8	19.2
	SD	4	6	5	-	2.3	2.8

Synopsis of Results

dose (mg/kg)	sex	No. of animals			prominent findings
		exposed	affected	deceased	in life		post mortem
					systemic	local
2000	male	5	1	0	signs of discomfort	none	none
2000	female	5	0	0	none	none	none

presence of clinical signs	1 d p.a.
full recovery of the survivors	yes
body weights	all animals gained weight in the weeks after dosing
sex differences	no
findings in life and post-mortem indicate	no toxic effects
LD50, dermal	> 2000 mg/kg body weight

Interpretation of results:

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

Conclusions:

No test substance related effects were noted from clinical observations or post-mortem examination at a dose of 2000 mg test substance per kg body weight.
The LD50, dermal of the test substance is > 2000 mg/kg body weight in rats.

Executive summary:

The Acute Dermal Toxicity assay for the test substance was performed (According to OECD 402 Guideline) in Sprague Dawley rats. One female group and one male group, of 5 animals each one, were treated with a single dose of 2000 mg/kg body weight (Limit test). The test material was applied via a patch to an area of approximately 6.5 x 8 cm on the dorsal thoracal region, and covered by a semi-occlusive dressing. The duration of the exposure was 24 hours.

Clinical observation was conducted at 0 - 0.5, > 0.5 - 1, > 1 - 2, > 2 - 4 and > 4 - 6 hours after administration of the test substance and then at least once a day for a total of 2 weeks. Body weight was controlled before the administration, 7 and 14 days after the administration. All animals were subjected to gross necropsy.

No test substance related effects were noted from clinical observations or post-mortem examination at a dose of 2000 mg test substance per kg body weight. The LD50dermal of the test substance was > 2000 mg/kg body weight in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The Acute Toxic Class Method assay (Limit Test) for the test substance was performed in rats (According to OECD 423 Guideline).Two groups of three fasted female was treated sequentially with a single oral dose of 2000 mg/kg bodyweight. The test material was administrated orally as an emulsion in corn oil.

Clinical sign and body weight were monitored during the study. All animals were subjected to gross necropsy (no relevant findings at post mortem examination were noted).

The Acute Dermal Toxicity assay for the test substance was performed (According to OECD 402 Guideline) in Sprague Dawley rats. One female group and one male group, of 5 animals each one, were treated with a single dose of 2000 mg/kg body weight (Limit test).The test material was applied via a patch to an area of approximately 6.5 x 8 cm on the dorsal thoracal region, and covered by a semi-occlusive dressing. The duration of the exposure was 24 hours.

Clinical observation was conducted at 0 - 0.5, > 0.5 - 1, > 1 - 2, > 2 - 4 and > 4 - 6 hours after administration of the test substance and then at least once a day for a total of 2 weeks. Body weight was controlled before the administration, 7 and 14 days after the administration. All animals were subjected to gross necropsy.

No test substance related effects were noted from clinical observations or post-mortem examination at a dose of 2000 mg test substance per kg body weight.

Data waiving:

According to REACH Annex VIII, Column 2, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely. In case of the product the exposure by inhalation during manufacturing of the product as well as during its use for the sealant production and use by the customer is unlikely.

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.