4,4,19,19-tetraethoxy-3,20-dioxa-8,15-dithia-4,19-disiladocosaneand S-(6-{[3-(triethoxysilyl)propyl]thio}hexyl) ethanethioate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11.11.2020 - 17.12.2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4,19,19-tetraethoxy-3,20-dioxa-8,15-dithia-4,19-disiladocosane and S-(6-{[3-(triethoxysilyl)propyl]thio}hexyl) ethanethioate

EC Number:

951-696-6

Molecular formula:

C17H36O4S2Si and C24H54O6S2Si2

IUPAC Name:

4,4,19,19-tetraethoxy-3,20-dioxa-8,15-dithia-4,19-disiladocosane and S-(6-{[3-(triethoxysilyl)propyl]thio}hexyl) ethanethioate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

Species/strain: WISTAR rats Crl: WI(Han)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: Female (non-pregnant and nulliparous)
Number of animals: 3 per step
Age at the
beginning of the study: 8 – 10 weeks
Body weight on the
day of administration: Step 1: 165 – 177 g;
Step 2: 173 – 186 g
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 Product Testing Muni ch GmbH
- 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 test item was administered at a single dose by gavage using a feeding tube.

Doses:

The starting dose was selected to be 2000 mg/kg body weight. No Compound related mortality was recorded in any animals of step 1. Based on these results and according to the acute toxic class method regime, 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:

Table 1: Volume of Test Item Applied per Animal

Animal No. / Sex Dose
(mg/kg bw) Body Weight on Day of Administration (g) Volume of Test Item Administered per Animal (mL)
1 / Female 2000 177 0.35
2 / Female 172 0.34
3 / Female 165 0.33
4 / Female 2000 173 0.35
5 / Female 186 0.37
6 / Female 174 0.35
 

Control animals:

no

Details on study design:

Preparation of the Animals
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 17 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 3 hours post dosing.

Observation Period
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 400-800 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.

Statistics:

Evaluation of Results
Results were interpreted according to OECD Guideline 423, Annex 2 and GHS.
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.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item showed no mortality but acute oral toxicity characteristics after a single dose administration at a dosage of 2000 mg/kg bw.

Clinical signs:

other: The most relevant clinical findings in the animals were reduced spontaneous activity, hunched posture, half eyelid closure, piloerection, ataxia and salivation. All animals recovered within 24 hours post-dose. Last time of observed effects were 4 (step 1)

Gross pathology:

No specific gross pathological changes were recorded for any animal.

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 associated with signs of toxicity but no mortality.
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): > 2000 mg/kg bw