2-ethoxy-1,3-dimethylcyclohexane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

This study was conducted between 23 June 2016 and 20 July 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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:

17 December 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:

EC No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

1

Reference substance name:

2-ethoxy-1,3-dimethylcyclohexane

EC Number:

944-610-3

Cas Number:

286472-48-8

Molecular formula:

C10H20O

IUPAC Name:

2-ethoxy-1,3-dimethylcyclohexane

Test material form:

liquid

Details on test material:

- Substance name as cited in test report: FRET 05-0293
- Phystical state: clear, colorless liquid
- Storage conditions: ambient temperature (15-25 °C), protected from light

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 170-172 g
- Fasting period before study: overnight
- Housing: in groups of three in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25”C
- Humidity (%): 30 - 70%
- Air changes (per hr): >15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 June 2016 To: 20 July 2016

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.
No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Study Design
In the absence of data regarding the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
Groups of fasted animals were treated as follows:
Dose Level (mg/kg) Concentration (mg/mL) Specific Gravity Dose Volume (mL/kg) Number of Rats
300 30 na 10 3
2000 na 0.840 2.39 3
2000 na 0.840 2.39 3

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 group to confirm the survival of the previously dosed animals.
The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
Individual body weights were recorded prior to dosing and 7 and 14 days after treatment.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. 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 were no deaths.

Clinical signs:

Hunched posture was noted 4 hours after dosing in one animal treated at a dose level of 2000 mg/kg. No signs of systemic toxicity were noted in the remaining animals during the observation period.

Body weight:

All animals showed expected gains in body weight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).
The test item does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures

Executive summary:

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Methods

A group of three fasted females was treated with the test item at a dose level of 300 mg/kg body weight.  Based on the results from this dose level, further groups of fasted females were treated at a dose level of 2000 mg/kg body weight.  Dosing was performed sequentially.

The test item was administered orally undiluted at a dose level of 2000 mg/kg body weight and as a solution in arachis oil BP at a dose level of 300 mg/kg body weight.  Clinical signs and body weight development were monitored during the study.  All animals were subjected to gross necropsy.

Results

Mortality.  There were no deaths.

Clinical Observations.  Hunched posture was noted 4 hours after dosing in one animal treated at a dose level of 2000 mg/kg.  There were no other signs of systemic toxicity noted.

Body Weight.  All animals showed expected gains in body weight.

Necropsy.  No abnormalities were noted at necropsy.

Conclusion

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

The test item does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.