A mixture of: propan-2-one-O,O'(methoxyvinylsilandiyl)dioxime; propan-2-one-O-(dimethoxyvinylsilyl)oxime; propan-2-one-O,O',O''-(vinylsilantriyl)trioxime

Acute Toxicity: dermal

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: propan-2-one-O,O'(methoxyvinylsilandiyl)dioxime; propan-2-one-O-(dimethoxyvinylsilyl)oxime; propan-2-one-O,O',O''-(vinylsilantriyl)trioxime

EC Number:

458-680-3

EC Name:

A mixture of: propan-2-one-O,O'(methoxyvinylsilandiyl)dioxime; propan-2-one-O-(dimethoxyvinylsilyl)oxime; propan-2-one-O,O',O''-(vinylsilantriyl)trioxime

Cas Number:

797751-44-1

Molecular formula:

not applicable, multiconstituent substance

IUPAC Name:

3-ethenyl-3-methoxy-6-methyl-2,4-dioxa-5-aza-3-silahept-5-ene; 5-ethenyl-2,8-dimethyl-5-{[(propan-2-ylidene)amino]oxy}-4,6-dioxa-3,7-diaza-5-silanona-2,7-diene; 5-ethenyl-5-methoxy-2,8-dimethyl-4,6-dioxa-3,7-diaza-5-silanona-2,7-diene

Test material form:

liquid

Test animals

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.

Administration / exposure

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

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.