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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

between 22nd February 2006 and 11th April 2006

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:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: April to May 2005 Date of signature: November 2005

Test type:

fixed dose procedure

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:

- Name of test material (as cited in study report): 2-(2-Vinyloxyethoxy)ethyl acrylate
- Substance type: Colourless liquid
- Physical state: liquid
- Analytical purity: > 99.7 %
- Lot/batch No.: 4V15-3101
- Expiration date of the lot/batch: 31st of July 2006
- Stability of test item: stable under storage conditions.
- Stability under test conditions: Unknown in PEG 300
- Storage condition of test material: In the refrigerator (range of 5 ± 3 °C), light protected.
- Other: Safety precautions: routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:

rat

Strain:

other: HanRcc:WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation:
Males: 9 - 10 weeks
Females: 12 - 13 weeks
- Weight at study initiation: The body weight of the animals was within the range commonly recorded for this strain and
age.

- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 63/05
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 deg C
- Humidity (%): between 30 and 70%
- Air changes (per hr): 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): light cycle of 12 hours light and 12 hours dark, music during the daytime light period.


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

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: not stated
- % coverage: approximately 10 %
- Type of wrap if used: covered with a semi-occlusive dressing. he dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL
- Concentration (if solution): 2000 mg/kg


VEHICLE:

The following information was provided by RCC Ltd:

Identification: Polyethylene glycol 300 (PEG 300)
Description: Colorless viscous liquid
Lot number: 11577905 1105271
Source: FLUKA Chemie GmbH, CH-9471 Buchs
Stability of vehicle: Stable under storage conditions;
expiration date: 19-JUL-2006
Storage conditions: At room temperature (range of 20 ± 5 °C), light protected.
Safety precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This formulation trial is excluded from the GLP statement of compliance.

The test item was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered at a volume dosage of 4 mL/kg. The application period was 24 hours.

Duration of exposure:

24 hours

Doses:

On test day 1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing.

No. of animals per sex per dose:

5 Males and 5 Females were treated with 2-(2-Vinyloxyethoxy)ethyl acrylate at 2000 mg/kg by dermal application.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:
Mortality / Viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (along with the clinical signs) and twice daily during days 2-15.

Body weights: On test days 1 (prior to administration), 8 and 15.

Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on te
st day 1. Once daily during days 2-15. All abnormalities were recorded.

Local signs: Once daily during days 2-15. All abnormalities were recorded.

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic signs of toxicity were observed during the study period. Vocaliation was noted in all animals during removal of the dressing on test day 2. Four males animals also vocalized during the examination of the skin on test day 2 and 3. The same was

Gross pathology:

All animals were killed at the end of the observation period by Carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained. No macroscopic findings were observed at necropsy

Other findings:

- Organ weights: No organs or tissues were retained.
- Other observations: None

Any other information on results incl. tables

Please see attachment 1 for the individual findings and the bodyweight tables.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of 2-(2-Vinyloxyethoxy)ethyl acrylate after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight

Executive summary:

Method:

The following guidelines were followed during this study:

OECD Guidelines for Testing of Chemicals, Section 4, Number 402 "Acute Dermal Toxicity", adopted February 24, 1987. Directive 92/69/EEC, B.3. "Acute Toxicity-Dermal", July 31, 1992.

Procedure:

Five male and five female HanRcc:WIST (SPF) rats were treated with 2-(2- Vinyloxyethoxy)ethyl acrylate at 2000 mg/kg by dermal application. The test item was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered at a volume dosage of 4 mL/kg. The application period was 24 hours.

Results:

No deaths occurred during the study. The body weight of the animals was within the range commonly recorded for this strain and age and no macroscopic findings were observed at necropsy.

Conclusion:

The median lethal dose of 2-(2-Vinyloxyethoxy)ethyl acrylate after single dermal administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat): greater than 2000 mg/kg body weight