Reaction mass of (4Z)-4-ethylidene-2-propoxycyclohexanol and (4E)-4-ethylidene-2-propoxycyclohexanol and (5Z)-5-ethylidene-2-propoxycyclohexanol and (5E)-5-ethylidene-2-propoxycyclohexanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliability 1 is assigned because the study conducted according to OECD TG 423 in compliance with GLP, without deviations that influence the quality of the results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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:

no

Test material

Test material information

1

Reference substance name:

Reaction mass of (4Z)-4-ethylidene-2-propoxycyclohexanol and (4E)-4-ethylidene-2-propoxycyclohexanol and (5Z)-5-ethylidene-2-propoxycyclohexanol and (5E)-5-ethylidene-2-propoxycyclohexanol

EC Number:

944-405-9

Molecular formula:

C11H20O2

IUPAC Name:

Reaction mass of (4Z)-4-ethylidene-2-propoxycyclohexanol and (4E)-4-ethylidene-2-propoxycyclohexanol and (5Z)-5-ethylidene-2-propoxycyclohexanol and (5E)-5-ethylidene-2-propoxycyclohexanol

Test material form:

liquid

Details on test material:

- Substance name as cited in test report: FRET 13-0156
- Phystical state: clear, yellowish liquid
- Storage conditions: ambient temperature (15-25 °C), protected from light

Specific details on test material used for the study:

Identification: IFF FRET 13-0156
Physical state/Appearance: Amber colored liquid
Storage Conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks of age
- Weight at study initiation: 140 - 173 g
- Fasting period before study: overnight fast immediately before dosing
- Housing: The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet and water (e.g. ad libitum): 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) was allowed throughout the study
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature was set to achieve limits of 19 to 25 °C
- Humidity (%): The relative humidity was set to achieve limits of 30 to 70%
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

2000 mg/kg dose level, the test item was used as supplied. 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.

Details on oral exposure:

In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Groups of fasted animals were treated as follows:

Dose level (mg/kg): 300
Concentration (mg/mL): 30
Dose volume (mL/kg): 10
Number of rats: 3 (female)

Dose level (mg/kg): 2000
Specific gravity: 0.954
Dose volume (mL/kg): 2.10
Number of rats: 2 groups of 3 (females)

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.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

3 females at 300 mg/kg
6 females at 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 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
- Necropsy of survivors performed: yes, 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.
- Body weights: Individual body weights were recorded prior to dosing and 7 and 14 days after treatment.

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 and ataxia were noted in the first group of animals treated at a dose level of 2000 mg/kg. Other signs of systemic toxicity noted in one of these animals were decreased respiratory rate, prostration and increased salivation. All animals in this group appeared normal 1 day after dosing.

No signs of systemic toxicity were noted during the observation period in animals treated at a dose level of 300 mg/kg and the second group of animals treated at a dose level of 2000 mg/kg

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:

other: Not classified according to CLP based on OECD TG No.423 study

Conclusions:

The acute oral toxicity test showed an LD50 of greater than 2000 mg/kg bw

Executive summary:

Acute oral toxicity: In this study (conducted to OECD TG No.423), 3 rats (females) were administered the substance at dose level of 300 mg/kg bw and 2 groups of 3 rats (females) were administered the substance at dose level of 2000 mg/kg bw.

The rats at 300 mg/kg bw showed no mortality, no clinical signs, expected gains in body weight, no abnormalities at necropsy.

The rats at 2000 mg/kg bw showed no mortality, expected gains in body weight, no abnormalities at necropsy. Hunched posture and ataxia were noted in the first group of animals treated at a dose level of 2000 mg/kg. Other signs of systemic toxicity noted in one of these animals were decreased respiratory rate, prostration and increased salivation. All animals in this group appeared normal 1 day after dosing.

No signs of systemic toxicity were noted during the observation period in the second group of animals treated at a dose level of 2000 mg/kg

The calculated acute oral LD50 for females was estimated to be greater than 2000 mg/kg bw.