Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 12, 2012 - November 29, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test method in accordance with OECD 423. GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
5-ethyl-2,8-dimethyl-5-[(propan-2-ylideneamino)oxy]-4,6-dioxa-3,7-diaza-5-silanona-2,7-diene
EC Number:
611-631-1
Cas Number:
58190-57-1
Molecular formula:
C11H23N3O3Si
IUPAC Name:
5-ethyl-2,8-dimethyl-5-[(propan-2-ylideneamino)oxy]-4,6-dioxa-3,7-diaza-5-silanona-2,7-diene
Details on test material:
- Name of test material (as cited in study report): EAC3
- Physical state: Liquid
- Analytical purity: 92.13%
- Lot/batch No.: 1000061820
- Expiration date of the lot/batch: 11 January 2013
- Storage condition of test material: Room temperature (15-25oC, below 70 RH%), protected from humidity.

Test animals

Species:
rat
Strain:
other: CRL:(WI)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: 10-11 weeks old
- Weight at study initiation: 230 – 240 g
- Fasting period before study: overnight
- Housing: 3 animals/cage, type II polypropylene/polycarbonate with lignocel bedding.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 22.5 °C
- Humidity (%): 37 – 69 %
- Air changes (per hr): 15 – 20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 250 mg/mL in the vehicle
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): BCBH2687V

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limit dose of 2500 mg/kg bw (requested by the sponsor).
Doses:
2500 mg/kg bw
No. of animals per sex per dose:
6 animals, 3 animals/group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter.
The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly after
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:
Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. At necropsy, after examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Mortality:
EAC3 did not cause mortality at a dose level of 2500 mg/kg bw.
Clinical signs:
Treatment with EAC3 at the dose level of 2500 mg/kg bw caused decreased activity (6/6), hunched back (6/6), prone position (4/6), incoordination (6/6), piloerection (5/6), creeping gait (3/6). All animals were symptom free from three days after the treatment.
Body weight:
Body weight gains of EAC3 treated animals during the study showed no indication of a test item-related effect.
Gross pathology:
No macroscopic observations were present at a dose level of 2500 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 value of the test item EAC3 was found to be greater than 2500 mg/kg bw in female CRL:(WI) rats.
Executive summary:

The single-dose oral toxicity of EAC3 was performed according to the acute toxic class method OECD 423 in CRL:(WI) rats. Two groups of three female rats were treated by gavage with the test item at a dose level of 2500 mg/kg bw. Initially, three females (Group 1) were treated and as no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group, therefore no further testing was required according to OECD 423. Clinical observations were performed for 14 days and all animals were subjected to a necropsy and a marcroscopic examination. All animals were clinical symptom (decreased activity, huncled back, prone position, incoordination, piloerection and creeping gait) free from three days after the treatment. Body weight gains showed no indication of a test item-related effect. No macroscopic observations were present at a dose level of 2500 mg/kg bw. Under the conditions of this study, the acute oral LD50 value of the test item EAC3 was found to be greater than 2500 mg/kg bw in female CRL:(WI) rats.