Acetamide, N,N'-(ethenylmethylsilylene)bis[N-ethyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 April - 31 August, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

Temperature and humidity recorded every hour

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[ethenyl(N-ethylacetamido)methylsilyl]-N-ethylacetamide

EC Number:

643-078-7

Cas Number:

87855-59-2

Molecular formula:

C11 H22 N2 O2 Si Si(CH3)(CH=CH2)[N(CH2CH3)(C(=O)CH3)]2

IUPAC Name:

N-[ethenyl(N-ethylacetamido)methylsilyl]-N-ethylacetamide

Test material form:

solid: compact

Details on test material:

Identification: ZMA T Number 4094103 (supplied as Dow Corning® 1-6008)
Lot Number: 091217
Expiration Date: 26 Dec 2010
Source: Korea Biogen Co., Ltd., 690 Sinduk-Ri, SungnamMyuan,
Chunan-City, Chungnam, 330-893, Korea
CAS Number: 87855-59-2
Physical Description: Amber liquid as determined by HES Study Number 11429-101
Stability: Stable
Purity: Based on the results of the characterization study, the
sample submitted is representative of test article and its
composition includes 77.9 ± 0.3% methylvinyl bis(nethylacetamido)silane.
Storage Conditions: Room temperature

Test animals

Species:

rat

Strain:

other: Crl: CD(SD) IGS BR VAF/Plus

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

300 mg/kg bw
2000 mg/kg bw

No. of animals per sex per dose:

3 female animals per dose

Control animals:

no

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the mortality results, under the conditions of this study, the LD50 is expected to be between 300 and 2000 mg/kg.

Executive summary:

This study was performed to evaluate Dow Corning® 1-6008 in an acute oral toxicity study in rats by oral gavage based on Organisation of Economic Co-operation and Development (OECD) Test Guideline Number: 423 (2001). Four groups of three fasted female rats received a single dose of test article. The dose level for the first two groups was 2000 mg/kg (Groups 1 and 2). The dose level for the second two groups was 300 mg/kg (Groups 3 and 4). Three animals assigned to 2000 mg/kg dose level groups died by Study Day 3. All of the animals assigned to the 300 mg/kg survived until the end of the 14 day observations. Observations most frequently noted in the animals assigned to 2000 mg/kg dose level groups and likely to be test article related were decreased activity behavior, clear or red soiling on the muzzle, and red and/or yellow soiling on the body. Decreased activity was noted in all the animals who received the 2000 mg/kg dose. In first set of three animals, it was noted between 20 and 40 minutes following dosing, not apparent at the following observation interval, and noted again and for the last time on the Study Day 1. In the second set of three animals at the 2000 mg/kg dose level, decreased activity was noted in two animals between three and four hours following dosing and in the third animal on Study Day 2. It was noted in two of those three animals until just prior to their being found dead; and in the remaining animal until Study Day 5. Clear soiling on the lower jaw was noted once in two animals between 20 and 40 minutes following dosing. It was noted on the muzzle of another animal between 20 and 40 minutes unti I Study Day 1. The red and/or yellow soiling was first noted on either Study Day 1 or 2 with a duration ranging from four to J 3 days in animals that survive until the end of the observation period. Other observations believed to be test article related was cold to touch and an arched back posture in one animal at the beginning of the observation period and thin body condition noted in another animal towards the end of the post dose observation period. Four out of the six animals assigned to the 300 mg/kg dose level had no notable clinical observations. The other two animals had notable clinical observations again likely to be test article related towards the end of the observation period. One of animals had thin body condition and the other had red soiling on the nose towards the end of the experimental phase. Notable body weight changes were observed at the 2000 mglkg dose level especially from Study Day 0 to Study Day 7. There was no notable body weight changes in five out of the six animals assigned to 300 mglkg dose level. The remaining animal from that dose level had a notable weight loss. In the 2000 mg/kg dose level groups, there were gross pathological findings believed to be test article related included multiple hemorrhagic regions, thickened glandular mucosa, nodule, multiple adhesions, erosion, ulcer and gaseous and/or watery contents in the stomach for both schedule sacrifice and found dead animals. There were also findings in the small intestines that included hemorrhage and abnormal contents in found dead animals. An acidie smell to the gastric and intestinal contents was also noted for one found dead animal. There were no gross visible lesions noted in three out of the six animals in 300 mg/kg dose level groups. Stomach findings, gaseous and abnormal contents, noted in the one affected animal were similar to but not as extensive those seen in the 2000 mg/kg dose level and considered test article related. Another animal had soiling noted on the nose. None of the animals at either dose level had any gross visible lesions associated with the cranial, oral, and thoracic cavities. Based on the mortality results, under the conditions of this study, the LD50 is expected to be between 300 and 2000 mg/kg.