(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Jun 2017 - 25 July 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

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

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:

(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

EC Number:

807-159-2

Cas Number:

69701-99-1

Molecular formula:

C10H16O4

IUPAC Name:

(2-ethyl-2-methyl-1,3-dioxolan-4-yl)methyl prop-2-enoate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch: 09892701
- Purity: 99.9%
- Physical state/ Appearance: clear colourless liquid
- Expiry Date: 06 March 2018
- 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: Envigo RMS (UK) Limited
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Fasting period before study:
- Housing: in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum, with the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing
- Water: ad libitum, with the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing
- Acclimation period: at leat 5 days

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

For the purpose of the study the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in arachis oil BP. For the purpose of the 2000 mg/kg dose level the test item was used as supplied

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.
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 mortality at a dose level of 2000 mg/kg, an additional group of 4 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.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

1 in the 300 mg/kg dose
5 n the 2000 mg/kg dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days.
- Frequency of individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes . 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

Preliminary study:

A sighting test has been conducted at dose levels of 300 mg/kg and 2000 mg/kg.

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:

other: Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were ataxia, hunched posture and lethargy. There were no signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg.

Gross pathology:

Abnormalities noted at necropsy of one animal treated at a dose level of 2000 mg/kg were ulcerated gastric mucosa, stomach adhered to the wall of the abdomen and thickened non-glandular epithelium of the stomach. No abnormalities were noted at necropsy
of the remaining animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD5o) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Executive summary:

Introduction
The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.
Methods
Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test item at a dose level of 2000 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. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were ataxia, hunched posture and lethargy. There were no signs of systemic toxicity noted in the animal treated at a dose level of 300 mg/kg.
Body Weight. Animals showed expected gains in body weight except for one animal treated at a dose level of 2000 mg/kg which showed body weight loss during the first week with expected gain in body weight during the second week.
Necropsy. Abnormalities noted at necropsy of one animal treated at a dose level of
2000 mg/kg were ulcerated gastric mucosa, stomach adhered to the wall of the abdomen and thickened non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of the remaining animals that were killed at the end of the study.
Conclusion
The acute oral median lethal dose (LDso) 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 - Category 5).