[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start date: 20 April 2017 Experimental completion date: 10 May 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

bis(cyclohexylmethyl) ether

Cas Number:

14315-63-0

Molecular formula:

C14H26O

IUPAC Name:

bis(cyclohexylmethyl) ether

Test material form:

liquid

Remarks:

Clear, colorless

Specific details on test material used for the study:

Identification: FRET 13-0460
Physical state/Appearance: clear colorless liquid
Storage Conditions: approximately 4 °C in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Animal Information
Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight at the start of treatment.
Animal Care and Husbandry
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

Test Item Preparation and Analysis
For the purpose of the 2000 mg/kg dose level, the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level, the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.
The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

Doses:

300 mg/kg and 2000 mg/kg

No. of animals per sex per dose:

at 300 mg/kg 1 female
at 2000 mg/kg 5 females

Control animals:

no

Details on study design:

In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.

In the absence of toxicity at a dose level of 300 mg/kg, an additional animal was treated at 2000 mg/kg.

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

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality, at 300 mg/kg or 2000 mg/kg.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period, at 300 mg/kg or 2000 mg/kg.

Gross pathology:

No abnormalities were noted at necropsy at 300 mg/kg or 2000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity test showed an LD50 of greater than 2000 mg/kg bw and is therefore not classified according to CLP criteria.

Executive summary:

FRET 13 -0460 was tested according to OECD Guideline for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Procedure” (2001)

Acute oral toxicity: In this study, 6 rats (0 males and 6 females) were administered the substance at dose levels of 300 mg/kg bw and 2000 mg/kg. The rats showed no mortality, clinical signs or treatment related effects at necropsy. All animals showed expected increases in bodyweight over the observation period, except for one animal treated at 2000 mg/kg, which showed no gain in body weight during the first week but expected gain in body weight during the second week.The acute oral LD50 for the substance in male and female rats was determined to be > 2000 mg/kg bw.