Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: OECD 423. GLP study: The acute oral LD50 value of the test item EAC3 was found to be greater than 2500 mg/kg bw in female rats.
Acute dermal toxicity: Based on the read-across approach from experimental data on analogue acetone oxime (test method OECD 402, GLP study), acute dermal LD50 of EAC3 was determined to be greater than 2493.77 mg/kg bw in male and female rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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.
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw
Quality of whole database:
The study is a GLP compliant and has Klimisch score 1. The quality of the database was determined as appropriate for assessment.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
EAC3 undergoes rapid hydrolysis in aqueous to acetone oxime and the corresponding ethylsilanetriol. Silanetriols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetone oxime and their values are comparable.
Principles of method if other than guideline:
Read-across approach from experimental data (according to OECD Guideline 402 and GLP) on analogue substance acetone oxime.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 493.77 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (read-across approach from an analogue)

See "Data Matrix" and "Reporting Format" attached.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on experimental data on the analogue acetone oxime (test method according to OECD 402 and GLP), the read-across approach was applied and the acute dermal LD50 of the test item EAC3 was determined to be greater than 2493.77 mg/kg body weight in male and female rats.
Executive summary:

An acute dermal toxicity study was performed with the analogue substance acetone oxime in CRL:(WI) rats, in compliance with OECD 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as supplied as a single dermal 24-hour exposure followed by a 14-day observation period. No effects were observed. The acute dermal LD50 of the analogue acetone oxime was found to be greater than 2000 mg/kg bw in male and female rats. Based on these results, the read-across approach was applied and the the acute dermal LD50 of EAC3 was determined to be greater than 2493.77 mg/kg bw in male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 493.77 mg/kg bw
Quality of whole database:
The study on the analogue substance is a GLP compliant and has Klimisch score 2. The quality of the database was determined as appropriate for assessment.

Additional information

Acute oral toxicity:

Key study: An acute oral toxicity test was performed on EAC3 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. 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.

Acute dermal toxicity:

Key study: Read-across from the analogue substance acetone oxime: An acute dermal toxicity study was performed with the analogue substance acetone oxime in CRL:(WI) rats, in compliance with OECD 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). No effects were observed. The acute dermal LD50 of the analogue acetone oxime was found to be greater than 2000 mg/kg bw in male and female rats. Based on these results, the read-across approach was applied and the acute dermal LD50 of EAC3 was determined to be greater than 2493.77 mg/kg bw in male and female rats.

Acute inhalation toxicity:

Data waiving (other justification): According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided. The information is provided for dermal route.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
Data waiving: According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided. The information is provided for dermal route.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Based on the available data on oral and dermal acute toxicity (LD50 > 2000 mg/kg bw), the substance 2 -propanone, 2,2',2''-[O,O',O''-(ethylsilylidyne)trioxime] (EAC) is not classified for acute toxicity according to CLP Regulation (EC) No 1272/2008.