2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Principles of method if other than guideline:

- Principle of test: similar to standard acute method (not further specified)
- Short description of test conditions: 15 male and 15 female rats were applied by gavage the test substance in doses up to 2500 mg/kg bw
- Parameters analysed / observed: deaths and clinical signs

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

EC Number:

233-487-5

EC Name:

2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

Cas Number:

10196-49-3

Molecular formula:

C6H15NOSi

IUPAC Name:

2,2,4-trimethyl-1,4,2-oxazasilinane

Specific details on test material used for the study:

OTHER SPECIFICS:
Kp. 140°C
technically pure

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Wistar II

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 170-205 g (males) and 180-200 g (females)
Please note: test results are also available for mouse, cat and dog.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not specified
- Amount of vehicle (if gavage): not specified

MAXIMUM DOSE VOLUME APPLIED: 1mL/100g bw

Doses:

50, 100, 250, 500, 1000, 1500, 1750, 2000, 2100, 2400, 2500 mg/kg bw (males)
250, 500, 1000, 1300, 1500, 2000, 2250 and 2500 mg/kg bw (females)

No. of animals per sex per dose:

15

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days

Statistics:

The calculation of the average lethal dose was based on LITCHFIELD and WILCOXON, J. Pharmacol. exper. Therap. 96, 99 (1949).

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 890 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 645 mg/kg bw

Based on:

test mat.

Mortality:

Males:
The lowest lethal dose (3 deaths of 15 animals after 1-3 days) was 1750 mg/kg bw. 11 of 15 animals and 13 of 15 animals died at a dose of 2000 (within 1 day) and 2100 mg/kg bw (within 1-4 days), respectively. At doses 2400 and 2500 mg/kg bw all 15 animals in each dose group died within one day.

Females:
The lowest lethal dose (1 death of 15 animals after 1 day) was 1300 mg/kg bw. 4 of 15 animals and 13 of 15 animals died at a dose of 1500 (within 1 day) and 2000 mg/kg bw (within 1 day), respectively. At doses 2250 and 2500 mg/kg bw all 15 animals in each dose group died within one day.

Clinical signs:

Poisoning signs such as breathing disorders, jumping cramps and reduction of the general condition were observed within 10 minutes (males) and 7 minutes (femlales) at a dose above or equal to 250 mg/kg bw and started within 2-3 minutes above or equal to 2000 (males) and 2250 (females) mg/kg bw. In animals, which did not die, clinical signs disappeared after 2-7 days (males) and 3-7 days (females).

Any other information on results incl. tables

Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]
Dose	Mortality (# dead/total)			Time range of deaths (hours)	Number with evident toxicity(#/total)
(mg/kg bw)	Male	Female	Combined		Male	Female	Combined
50	0/15	not tested	n/a	--	0/15	not tested	n/a
100	0/15	not tested	n/a	--	0/15	not tested	n/a
250	0/15	0/15	0/30	--	15/15	15/15	30/15
500	0/15	0/15	0/30	--	15/15	15/15	30/15
1000	0/15	0/15	0/30	--	15/15	15/15	30/15
1300	not tested	1/15	n/a	24	not tested	15/15	n/a
1500	0/15	4/15	4/30	24	15/15	15/15	30/15
1750	3/15	not tested	n/a	24-72	15/15	not tested	n/a
2000	11/15	13/15	24/30	24	15/15	15/15	30/15
2100	13/15	not tested	n/a	24-96	15/15	not tested	n/a
2250	not tested	15/15	n/a	24	not tested	15/15	n/a
2400	15/15	not tested	n/a	24	15/15	not tested	n/a
2500	15/15	15/15	30/30	24	15/15	15/15	30/15

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 of the test substance in male and female rats was 1890 and 1645 mg/kg bw, respectively.

Executive summary:

In an acute oral toxicity study, 15 male and 15 female Wistar II strain rats per dose group were given a single oral dose of the test substance by gavage at a doses of 50, 100, 250, 500, 1000, 1500, 1750, 2000, 2100, 2400 and 2500 mg/kg bw (males) and 250, 500, 1000, 1300, 1500, 2000, 2250 and 2500 mg/kg bw (females) and were observed for 7 days.

Death in males started at a dose of 1750 mg/kg bw with 3/15 dead males within 1-3 days and death in females started at a dose of 1300 mg/kg bw with 1/15 dead female within 1 day. The LD50 was reported to be 1890 mg Aktiv. MO/kg bw (males) and 1645 mg Aktiv. MO/kg bw (females), respectively.

Clinical signs were breathing disorders, jumping cramps and reduction of the general condition within 10 minutes (males) and 7 minutes (females) at a dose above or equal to 250 mg/kg bw. linical signs were breathing disorders, jumping cramps and reduction of the general condition within 10 minutes (males) and 7 minutes (females) at a dose above or equal to 250 mg/kg bw.

The surviving animals had recovered from the symptoms until day 7.

Further results are available for mouse, cat and dog showing LD50 of >1000 mg/kg bw, 500 mg/kg bw and >250 mg/kg bw, respectively. However, the LD50 value for mice and dog are only estimates since the highest concentration used was 1000 mg/kg bw and 250 mg/kg bw. Furthermore, the total number of animals, i.e. 2 cats and 2 dogs, is not sufficient for a reliable dervation of a LD50 value and due to the preference of rats as suitable test animal for classification and labelling according to OECD guideline recommendation, the LD50 values in the present study report obtained with this species were used for classification and labelling according to regulation (EC) 1272/2008 (CLP).

Oral LD50 (rat, males/females) < 2000 mg/kg bw