Butanedioic acid, 1-[2-[(1-oxo-2-propen-1-yl)oxy]ethyl] ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 16 May 2006 and 15 June 2006.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of Inspection: 30th August 2005 Date of signature: 21 November 2005

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

478-130-6

EC Name:

-

Cas Number:

50940-49-3

Molecular formula:

C9H12O6

IUPAC Name:

2-(acryloyloxy)ethyl hydrogen succinate

Details on test material:

Sponsor's identification : MAES :
Description : colourless turbid liquid
Batch number : J417708-A
Date received : 29 March 2006
Storage conditions : room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Female Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant.
After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).

The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK) was allowed throughout the study.
The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

Procedure
Using available information on the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (mg/ml) (ml/kg) Female
300 30 10 3
2000 - 1.63 3
300 30 10 3

- = not applicable

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 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.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. 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.

Doses:

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

No. of animals per sex per dose:

3 animals per dose, 3 dose groups.

Control animals:

no

Details on study design:

- Duration of observation period following administration:
The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2, and 4 hours after dosing and subsequently once daily for up to fourteen days.

- Frequency of observations and weighing:
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.

- 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:

ca. 775 mg/kg bw

Based on:

test mat.

95% CL:

> 300 - < 2 000

Mortality:

All animals treated at a dose level of 2000 mg/kg were found dead two, four hours or one day after dosing. There were no deaths noted in animals treated at a dose level of 300 mg/kg.

Clinical signs:

other: Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, lethargy, ataxia, pilo-erection and decreased respiratory rate. There were no signs of systemic toxicity noted in animals treated at a dose level of 30

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic or abnormally red lungs, dark liver, dark kidneys, gaseous stomach and haemorrhage, ulceration and epithelial sloughing of the gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was approximately 775 mg/kg bw (Globally Harmonised Classification System Category 4 >300 and <2000 mg/kg bw).

Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

- OECD Guidelines for the Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 17 December 2001).

- Method B1 tris Acute Toxicity (Oral) of Commission Directive 2004/73/EC

Method. A group of three fasted females was treated with the test material at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at dose levels of 2000 and 300 mg/kg bodyweight. Dosing was performed sequentially. The test material was administered orally as a solution in arachis oil BP for the 300 mg/kg dose level and orally undiluted for the 2000 mg/kg dose level. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths noted in animals treated at a dose level of 300 mg/kg. All animals treated at a dose level of 2000 mg/kg were found dead two, four hours or one day after dosing.

Clinical Observations. There were no signs of systemic toxicity noted in animals treated at a dose level of 300 mg/kg. Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were hunched posture, lethargy, ataxia, pilo-erection and decreased respiratory rate.

Bodyweight. The surviving animals showed expected gains in bodyweight over the study period.

Necropsy. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic or abnormally red lungs, dark liver, dark kidneys, gaseous stomach and haemorrhage, ulceration and epithelial sloughing of the gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Conclusion. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was approximately 775 mg/kg bodyweight (Globally Harmonised Classification System Category 4 >300 and < 2000 mg/kg bw).