Trimethoxy(3,3,3-trifluoropropyl)silane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start date (initial animal arrival): 20 August 2020 ; Experimental completion data (final macroscopic examination): 29 September 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trimethoxy(3,3,3-trifluoropropyl)silane

EC Number:

207-059-3

EC Name:

Trimethoxy(3,3,3-trifluoropropyl)silane

Cas Number:

429-60-7

Molecular formula:

C6H13F3O3Si

IUPAC Name:

trimethoxy(3,3,3-trifluoropropyl)silane

Test material form:

liquid

Specific details on test material used for the study:

Test item: ST2092NM
Appearance: Clear colorless liquid
Storage conditions: Ambient 10 to 30°C
Stored in darkness, may be used/formulated in light
Batch number: 802496
Expiry date: 31 October 2020
Purity: 100%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: female RccHan™:WIST albino rats were obtained from Envigo RMS (UK) Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately eight to twelve weeks
- Weight at study initiation: 157 to 164 g. The body weight variation did not exceed  20% of the mean body weight of any previously treated animals.
- Fasting period before study: Overnight prior to dosing
- Housing: The cages were solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved softwood bark-free fiber bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals. Each cage of animals was provided with Aspen chew blocks or balls for environmental enrichment. Chew blocks or balls were provided throughout the study and were replaced when necessary. Each cage of animals was provided with a plastic shelter for environmental enrichment, which was replaced at the same time as the cages.
- Diet (e.g. ad libitum): animals were allowed free access to a standard rodent diet (Teklad 2014C Diet), except for overnight prior to and approximately four hours after dosing.
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: At least five days before treatment.
- Method of randomisation in assigning animals to test and control groups: The animals were allocated without conscious bias to cages within the treatment groups. They were housed in groups of one or four rats.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature controls were set to maintain the range of 20 to 24°C
- Humidity (%): relative humidity controls were set to maintain the range of 40 to 70%
- Air changes (per hr): The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light): Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Formulation:
The test item was formulated at concentrations of 30 and 200 mg/mL in the vehicle, by adding the vehicle to the test item and mixing. The formulation was administered at a volume of 10 mL/kg body weight.
The test item formulations were prepared on the day of dosing.

Design:
In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Two single animals were treated 300 and 2000 mg/kg (1 animal per dose)

In the absence of mortality or toxicity at a dose level of 2000 mg/kg, an additional group of 4 animals was treated at 2000 mg/kg

Dose administration:
The appropriate dose volume of the test item was administered to each rat by oral gavage using a plastic syringe and plastic catheter.
A record of the weight of each formulation dispensed and the amount remaining after dosing was made. The balance of these two weights was compared with the predicted usage as a check that the doses had been administered correctly.
Formulations were stirred before and throughout the dosing procedure.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

1 animal at 300 mg/kg
5 animals at 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of any clinical signs and the time were recorded at each observation.
The weight of each rat was recorded on Days -1, 1 (prior to dosing), 8 and 15. Individual weekly body weight changes and group mean body weights were calculated.

- Necropsy of survivors performed: yes - All animals were humanely killed on Day 15 by carbon dioxide asphyxiation and subsequently exsanguinated. All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of the brain, cecum, duodenum, heart, kidneys, small and large intestine, liver, lungs and bronchi, spleen, stomach, subcutaneous tissue and urinary bladder was recorded.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no clinical signs of reaction to treatment throughout the study.

Gross pathology:

Macroscopic examination at study termination on Day 15 revealed enlarged, swollen, or thickened tissues of the kidneys (measured at 30 x 20 mm or 20 x 25 mm) in two females, noted to be filled with red watery fluid, pale lesions on the surface and a spongy texture. No abnormalities were revealed in any other animal at the macroscopic examination at this time.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

EU CLP: Not classified

Conclusions:

The acute median lethal oral dose (LD50) to rats of the test item was demonstrated to be greater than 2000 mg/kg body weight.
The test tiem is included in Category 5/Unclassified, according to the Globally Harmonised System (GHS)

Executive summary:

Summary

The study was performed to assess the acute oral toxicity of the test item, to the rat.

Fasted female rats received a single oral gavage dose of the test item, formulated in corn oil, at the following dose levels:

Sighting investigations: 300 and 2000 mg/kg body weight

Main study: Based on the results of the sighting investigations a further four fasted females were similarly dosed at 2000 mg/kg body weight.

During the study, clinical condition, body weight and macropathology investigations were undertaken.

Results

There were no deaths or clinical signs observed throughout the study.

All animals were considered to have achieved satisfactory body weight gains throughout the study.

Macroscopic examination at study termination on Day 15 revealed enlarged, swollen, or thickened tissues of the kidneys in two females, noted to be filled with red watery fluid, pale lesions on the surface and a spongy texture. No abnormalities were revealed in any other animal at the macroscopic examination at this time.

Conclusion

The acute median lethal oral dose (LD₅₀) to rats of the test item was demonstrated to be greater than 2000 mg/kg body weight.