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

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

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: Modified test according to Lim et al., 1961. Thirty male rats were exposed to 2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane applied in increasing concentrations for 5 days and subsequently observed for one week. The concentrations of the test item were increased by a factor of 1.5, i.e. 329, 494, 740, 1110 and 1666 mg/kg bw.
- Short description of test conditions: not specified
- Parameters analysed / observed: Mortality, cumulative LD50 was determined.

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

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:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: Diluted in water.

OTHER SPECIFICS:
Kp. 140°C
technically pure

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Wistar II

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

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

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

5 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

329 mg/kg bw/day (nominal)

Remarks:

dose at day 1

Doses / concentrations 2

Dose / conc.:

494 mg/kg bw/day (nominal)

Remarks:

dose at day 2

Doses / concentrations 3

Dose / conc.:

740 mg/kg bw/day (nominal)

Remarks:

dose at day 3

Doses / concentrations 4

Dose / conc.:

1 110 mg/kg bw/day (nominal)

Remarks:

dose at day 4

Doses / concentrations 5

Dose / conc.:

1 666 mg/kg bw/day (nominal)

Remarks:

dose at day 5

No. of animals per sex per dose:

30

Control animals:

no

Details on study design:

- Dose selection rationale: The test was conducted according to the method described by Lim et al., 1961.

Examinations

Observations and examinations performed and frequency:

MORTALITY: Yes

CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No
-

Sacrifice and pathology:

GROSS PATHOLOGY: No

HISTOPATHOLOGY: No

Statistics:

The cumulative LD50 was determined from the arithmetic mean of 5 consecutive doses at which 50% of the animals died. The cumulative factor was determined from the ratio LD50 acute/LD50 cum.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Symptoms of toxicity were observed in all rats at every dose level

Mortality:

mortality observed, treatment-related

Description (incidence):

At 1110 mg/kg bw 3 of 30 animals died and at 1666 mg/kg bw 15 of 30 animals were found dead

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not specified

Effect levels

Key result

Dose descriptor:

other: LD50

Remarks:

cumulative

Effect level:

868 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male

Basis for effect level:

mortality

Target system / organ toxicity

Key result

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Results of repeated dose application

Experimental day	Dose [mg/kg bw]	Result [deaths/clinical signs/total number of animals]
1.	329	0/30/30
2.	494	0/30/30
3.	740	0/30/30
4.	1110	3/30/30
5.	1666	15/30/30
6.-13.	-	15/30/30

Applicant's summary and conclusion

Conclusions:

The cumulative LD50 for repeated dose toxicity oral was 868 mg/kg bw.

Executive summary:

In a repeated dose oral toxicity study, 30 male Wistar II strain rats were given increasing doses of the test substance by gavage over 5 days. The doses were augmented by a factor of 1.5 resulting in the following doses: 329, 494, 740, 1110 and 1666 mg/kg bw. Death occurred at a dose of 1110 mg/kg bw with 3/30 dead males at day 4 and at day 5 with a dose of 1666 mg/kg bw. The cumulative LD50 was reported to be 868 mg Aktiv. MO/kg bw (males). Clinical signs were not specified but symptoms of toxicity were recorded for all animals at every dose level.

Oral LD50 cum. (rat, males) = 868 mg/kg bw