Trimethyl(octadecyloxy)silane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-03-01 to 2018-03-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Adopted December 17, 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

Adopted May 30, 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Trimethyl(octadecyloxy)silane

EC Number:

242-554-8

EC Name:

Trimethyl(octadecyloxy)silane

Cas Number:

18748-98-6

Molecular formula:

C21H46OSi

IUPAC Name:

trimethyl(octadecyloxy)silane

Test material form:

liquid

Details on test material:

Chemical Name: Octadecyloxytrimethylsilane
CAS No.: 18748-98-6
EINECS No.: 242-554-8
Appearance: Clear, Colourless Liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Housing and Feeding Conditions
- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
The test item was administered at a single dose by gavage using a feeding tube.
For liquids the test itam was administered according to the chosen starting dose (2000 mg/kg body weight)

Doses:

The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1. Based on these results and according to the acute toxic class method regime a second step was required. A second step was performed at a dose of 2000 mg/kg body weight. No compound related mortality was recorded for any animal of step 2. Based on these results and according to the acute toxic class method regime no further testing was required.

No. of animals per sex per dose:

3 per step (2 steps performed)

Control animals:

no

Details on study design:

All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
Weight Assessment
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
Clinical Examination
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Pathology
At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally at a dosage of 250-400 mg/kg bw.
All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.

Evaluation of Results
Results were interpreted according to OECD Guideline 423, Annex 2.
Individual reactions of each animal were recorded at each time of observation.
Toxic response data were recorded by dose level.
Nature, severity and duration of clinical observations were described.
The body weight changes were summarised in a tabular form.
Necropsy findings were described.
With few exceptions, data were captured using the validated departmental computerised system E WorkBook (version 10.1.2, ID Business Solutions Ltd.).

Statistics:

According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the
results is not regarded as necessary.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Limit dose tested: 2000 mg/kg body weight

Mortality:

No mortality observed until the end of the study period

Clinical signs:

other: unspecific clinical signs werer observed up to 3 h after oral application i.e. slightly reduced spontaneous activity, slight piloerection, hunched posture, half eyelid-closure

Gross pathology:

No macroscopically visible changes were observed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, a single oral application of the test item to rats at a dose of 2000 mg/kg body weight was not associated with mortality. Unspecific clinical signs were obseverd up to 3 h after oral application.
The median lethal dose of the test item after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): > 5000 mg/ kg bw

Executive summary:

Under the conditions of the present study, a single oral application of the test item at a dose of 2000 mg./kg body weight was not associated with mortality. Unspecific clinical signs were obseverd up to 3 h after oral application.

The median lethal dose of the test item after a single oral administration to female rats, observed over a period of 14 days is:

LD₅₀cut-off (rat): > 5000 mg/ kg bw