Isobutylisopropyldimethoxysilane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 December 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in accordance with EC Guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

yes

Remarks:

Only 3M/3F per dose group.

Principles of method if other than guideline:

The study was performed according to EC-test guidelines, which provided an animal number of 5F/5M per dose group. Divergent from that, only 3M/3F animals per dose group were employed in the study, since this procedure leads to equivalent results.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isobutylisopropyldimethoxysilane

EC Number:

402-580-4

EC Name:

Isobutylisopropyldimethoxysilane

Cas Number:

111439-76-0

Molecular formula:

Hill formula: C9H22O2Si

IUPAC Name:

dimethoxy(2-methylpropyl)(propan-2-yl)silane

Details on test material:

IUPAC name: Dimethoxyisobutylisopropyl silane
ZK 119.649 (TZ 01748), batch no. W87/138 (certificate of analysis no. 87/003, dated Jan. 26, 1988).
Stability of ZK 119.649: stored in closed vessels, at room temperature at least stable till Apr./May 1988

Test animals

Species:

rat

Strain:

other: Wistar-Han-Schering

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering
- Age at study initiation: No data
- Weight at study initiation: (I): 79 to 98 g, (IIa): 76 to 91 g, (IIb): 95 to 117 g
- Fasting period before study: 18.5 to 19.5 hours
- Housing: Conventional
- Diet (e.g. ad libitum): pell. Altromin R ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22°C
- Humidity (%): 52-66%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Isotonic sodium chloride solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: No data
- Amount of vehicle (if gavage): Control groups: 1.25 mL vehicle/kg or 2.5 mL vehicle/kg
- Justification for choice of vehicle: No information
- Lot/batch no. (if required): Batch no. KL 150 A2
- Purity: 1L contains 9.0 g sodium chloride

MAXIMUM DOSE VOLUME APPLIED: No data

Doses:

Two doses: 1.09 mg/kg bw/day (female only) and 2.18 mg/kg bw/day ( male and female)

No. of animals per sex per dose:

1.09 mg/kg bw/day: 3 female
Control (1.25 mL vehicle/kg): 3 female
2.18 mg/kg bw/day: 3 female + 3 male
Control (2.5 mL vehicle/kg): 3 female + 3 male

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighings on day 1, day 8 and day 14. Clinical observations performed on day 1, 30 mins, 1.5 hr and 3hr after exposure and then daily.
- Necropsy of survivors performed: yes
- Other examinations performed: None

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 180 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 090 mg/kg bw

Based on:

test mat.

Mortality:

One female animal treated with 2.18 g ZK 119.649/kg died on day 3 of the test.

Clinical signs:

other: other: The main findings after application of ZK 119.649/kg in male and female animals were apathy, disturbances in gait and breathing, eyelid closure (incomplete), ruffled fur and wet fur sticking together. Male animals revealed, additionally, lateral po

Gross pathology:

In animals which died before the end of the observation period: In animal no. 11F which died on day 3 of the study a yellowish mucous content within the small intestine as well as a reddening of mucosa of the urinary bladder were observed.
In animals sacrificed at the end of the observation period: none

Other findings:

None

Any other information on results incl. tables

Application schedule of ZK 119.649 and rate of mortality:

Dose (g/kg)	No. of animals, sex	Observation period after administration (time of administration)	D/U
1.25 mL vehicle /kg (control)	3 F	25 Aug to 7 Sept 1987 (9:55 to 10:10)	0/3
1.09	3F		0/3
2.5 mL vehicle /kg (control)	3M	11 Aug to 24 Aug 1987 (9:55 to 10:05)	0/3
2.18	3M		0/3
2.5 mL vehicle /kg (control)	3F	13 Aug to 26 Aug 1987 (11:00 to 11:15)	0/3
2.18	3F		1/3

 

D: No. of dead animals

U: No. of animals used

Clinical findings after application of 2.18 g ZK 119.649/kg in male rats

Dose (g/kg)	Findings	Number of animals with findings/number of surviving animals
		Day 1 + 30 min	Day 1 + 1.5 hr	Day 1 + 3 hr	Day 2	Day 3	Days 4 - 14
2.5 mL/kg vehicle (control)	without findings	3/3	3/3	3/3	3/3	3/3	3/3
2.18	apathy, slight apathy, severe lateral position conscious gait, atactic gait, severely atactic tremor, total, spontaneous respiration, irregular incomplete eyelid closure fur, ruffled fur, wet, sticking together without findings	3/3             3/3	3/3           0/3	3/3               1/3   0/3	1/3 1/3 1/3   1/3 1/3 1/3 1/3 2/3 0/3	2/3 1/3	3/3

Clinical findings after application of 2.18 g resp. 1.09 g ZK 119.649/kg in female rats

Dose (g/kg)	Findings	Number of animals with findings/number of surviving animals
		Day 1 + 30 min	Day 1 + 1.5 to 2 hr	Day 1 + 3 to 3.5 hr	Day 2	Day 3	Days 4 - 14
1.25 mL/kg vehicle (control)	without findings	3/3	3/3	3/3	3/3	3/3	3/3
1.09	gait, atactic without findings	3/3	3/3	3/3 0/3	3/3	3/3	3/3
2.5 mL/kg vehicle (control)	without findings	3/3	3/3	3/3	3/3	3/3	3/3
2.18 g	apathy, severe prone, lateral or supine position in state of unconsciousness gait, atactic gait, severely atactic disturbances in breathing incomplete eyelid closure dacryorrhea, slight fur, wet, sticking together fur, ruffled without findings	3/3	3/3           2/3 0/3	1/3 2/3         2/3 0/3	1/3 1/3       1/3 1/3 1/3 1/3   0/3	2/2	2/2

Body weight in g at the start (day 1), day 8 and day 14 of the test in male rats

Dose (g/kg)	No. of animals, sex	Animal nos.	Day 1 X/SD	Day 8 X/SD	Day 14 X/SD
2.5 mL/kg vehicle (control	3 M	1 M 2 M 3 M	91/4	149/2	183/10
2.18	3 M	4 M 5 M 6 M	89/10	144/11	180/13

Body weight in g at the start (day 1), day 8 and day 14 of the test in female rats

Dose (g/kg)	No. of animals, sex	Animal nos.	Day 1 X/SD	Day 8 X/SD	Xi	Day 14 X/SD	Xi
1.25 mL/kg vehicle (control	3 F	1 F 2 F 3 F	107/11	150/4			161/7
1.09	3 F	4 F 5 F 6 F	111/5	152/5			166/6
2.5 ml vehicle/kg (control)	3 F	7 F 8 F 9 F	85/8	137/11		150/12
2.18	3 F	10 F 11 F 12 F	88/3		136   124		149   144

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 determination after a single i.g. application of ZK 119.649 yielded in male rats a dose > 2.18 g ZK 119.649/kg and in female rats a dose > 1.09 g/kg, presumably close to 2.18 g ZK 119.649/kg. No clear cut differences between surviving male and female animals of dose group 2.18 g/kg were observed in respect of clinical observations, body weight gain and autopsy findings.
Derived from the findings of the present study it is concluded that the LD50 in the rat is > 2 g/kg. Therefore, ZK 119.649 is not classified as "harmful'.

Executive summary:

For the toxicological characterization of ZK 119.649 an acute toxicity study with approximate LD50 determination in rats (M+F) was

to be performed after a single intragastric (i.g.) application.

The LD50 determination after a single i.g. application of ZK 119.649 yielded in male rats a dose > 2.18 g ZK 119.649/kg and in female rats a dose > 1.09 g/kg, presumably close to 2.18 g ZK 119.649/kg. No clear cut differences between surviving male and female animals of dose group 2.18 g/kg were observed in respect of clinical observations, body weight gain and autopsy findings.

Derived from the findings of the present study it is concluded that the LD50 in the rat is > 2 g/kg. Therefore, ZK 119.649 is not classified as "harmful'.