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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

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:
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 levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 890 mg/kg bw
Based on:
test mat.
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

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