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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

Constituent 1
Chemical structure
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 / concentrationsopen allclose all
Dose / conc.:
329 mg/kg bw/day (nominal)
Remarks:
dose at day 1
Dose / conc.:
494 mg/kg bw/day (nominal)
Remarks:
dose at day 2
Dose / conc.:
740 mg/kg bw/day (nominal)
Remarks:
dose at day 3
Dose / conc.:
1 110 mg/kg bw/day (nominal)
Remarks:
dose at day 4
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