2-Propenoic acid, 2-[2-(ethenyloxy)ethoxy]ethyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between: 10th September 2003 and 07th November 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

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)

Remarks:

Date of inspection: November 2002 Date of Signature: March 2003

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

451-690-9

EC Name:

-

Cas Number:

86273-46-3

Molecular formula:

C9H14O4

IUPAC Name:

2-[2-(ethenyloxy)ethoxy]ethyl prop-2-enoate

Test material form:

other: liquid

Details on test material:

The following information was provided by the sponsor:

Identification: 2-(2'-Vinyloxy ethoxy) ethyl acrylate
Description: Colourless liquid
Lot number: 2C02-3323-A2
Purity: 99.6%
physical state: liquid
Stability of test item: Stable under storage conditions
Expiry date: 31-JAN-2004
Stability of test item dilution: Unknown in PEG 300; is excluded from the statement of compliance.
Storage conditions: in the refrigerator (range of 5 ± 3 °C), protected from light.
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:

rat

Strain:

other: HanBrl: Wist (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:RCC Ltd, Laboratory Animal Services, CH-4414 Fullinsdorf, Switzerland

- Age at study initiation: 12 weeks

- Fasting period before study: Approximately between 17 and 18 hours.

- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz,Switzerland).

- Diet (e.g. ad libitum):Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch No. 4/03 and 54/03 (Provimi Kliba AG. CH-4303, Kaiseraugst, Switzerland, ad libitum

- Water (e.g. ad libitum): Community tap water from Fullinsdorf in Switzerland ad libitum.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 19 deg C to 25 deg C.

- Humidity (%): Set to achieve limits of 30 to 70%.

- Air changes (per hr): The rate of air exchanges was 10 to 15 changes per hour.

- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark.

IN-LIFE DATES: From: Day 0 To: end of study

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test item was diluted in vehicle (PEG 300) at concentrations of 0.2 g/mL and 0.03 g/ml, respectively and administered at a volume dosage of 10 mL/kg.

- Amount of vehicle (if gavage): 10ml/kg

- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This trial formulation is excluded from the GLP statement of compliance. PEG 300 was found to be a suitable vehicle.

- Lot/batch no. (if required): 448174/1 21203148

MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg

The test material was administered orally undiluted at a dose level of 2000 mg/kg, and as a solution in arachis oil BP at a dose level of 300 mg/kg.

Dosing was performed sequentially.

DOSAGE PREPARATION (if unusual):
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group and each dose level to confirm the survival of the previously dosed animals.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose levels are in terms of the test item as supplied by the sponsor. In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

Doses:

300 (with vehicle) and 2000 (undiluted) mg/kg.

No. of animals per sex per dose:

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

Control animals:

no

Details on study design:

- Duration of observation period following administration: 18 days


- Frequency of observations and weighing: Observations were monitored during acclimitisation and at approximately 1, 2, 3 and 5 hours after dosing and daily from day 2 to 18.


- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, necropsy.

Statistics:

None recorded.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All 2000 mg/kg treated animals were found dead 5 hours after treatment.

Clinical signs:

other: Slightly ruffled fur with hunched posture was noted in all 2000 mg/kg treated animals 3 hours after administration, No clinical signs were observed in the 300 mg/kg treated animals during the course of the study.

Gross pathology:

All animals which died spontaneously during the observation period were necropsied as soon as they were found dead. All surviving animals were killed at the end of the observation period by an intraperitoneal injection of Vetanarcol at a dose of at least 2.0 mUkg body weight (equivalent to at least 324 mg sodium pentobarbitone/kg body weight) and discarded after macroscopic examinations were performed. No organs or tissues were retained. No macroscopic findings were recorded at necropsy.

Other findings:

- Organ weights: not retained

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The median lethal dose of 2-(2'-Vinyloxy ethoxy) ethyl acrylate after single oral administration to female rats, observed over a period of 14 days is:
300 mg/kg body weight < LD50 (female rat) < 2000 mg/kg body weight.

Executive summary:

Three groups, each of three female HanBrl: WIST (SPF) rats were treated with 2-(2'Vinyloxy ethoxy) ethyl acrylate by oral gavage administration at a dosage of 2000 mg/kg or 300 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at concentrations of 0.2 g/mL and 0.03 g/ml, respectively and administered at a volume dosage of 10 mL/kg. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded twice daily during test days 1-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. The following females were treated and percentage of mortality was observed: 2000 mg/kg: 100% and 300 mg/kg: 0%.

All 2000 mg/kg treated animals were found dead 5 hours after treatment. Slightly ruffled fur with hunched posture was noted in all 2000 mg/kg treated animals 3 hours after administration. No clinical signs were observed in the 300 mg/kg treated animals during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.