[2-[(2-methyl-1-oxoallyl)oxy]ethyl] hydrogen succinate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October - November 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[2-[(2-methyl-1-oxoallyl)oxy]ethyl] hydrogen succinate

EC Number:

244-096-4

EC Name:

[2-[(2-methyl-1-oxoallyl)oxy]ethyl] hydrogen succinate

Cas Number:

20882-04-6

Molecular formula:

C10H14O6

IUPAC Name:

4-{2-[(2-methylprop-2-enoyl)oxy]ethoxy}-4-oxobutanoic acid

impurity 1

Reference substance name:

2-hydroxyethyl methacrylate

EC Number:

212-782-2

EC Name:

2-hydroxyethyl methacrylate

Cas Number:

868-77-9

Molecular formula:

C6H10O3

IUPAC Name:

2-hydroxyethyl methacrylate

impurity 2

Reference substance name:

Succinic acid

EC Number:

203-740-4

EC Name:

Succinic acid

Cas Number:

110-15-6

Molecular formula:

C4H6O4

IUPAC Name:

succinic acid

Test material form:

liquid

Details on test material:

- Name as cited in the report: Methacryloyloxyethyl succinate
- EC-name: [2-[(2-methyl-1-oxoallyl)oxy]ethyl] hydrogen succinate
- CAS: 20882-04-6
- EC-No.: 244-096-4
- Batch No.: 3903/64
- Storage: 4-8°C, protected from heat and sunlight
- Description: yellowish liquid
- Density: 1.1884 g/kg
- Molecular weight: approx. 230 g/mol
- Formula: C10H14O6
- Purity: 84% (NMR)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

ANIMALS

- Species/strain: WISTAR rats Crl: WI(Han)
- Source: Charles River, 97633 Sulzfeld, Germany
- Sex: female (non-pregnant and nulliparous)
- Number of an im als: 3 per step
- Age at the beginning of the study: 8-9 weeks old
- Body weight on the day of administration: step 1: 155 - 161 g; step 2: 143 -164 g

The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.

HOUSING & FEEDING

- Full barrier in an air-conditioned room
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0631)
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control , microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 02102150820)
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.

Doses:

The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.

No. of animals per sex per dose:

3 per step

Control animals:

no

Details on study design:

It is the principle of the acute toxic class method that, based on a stepwise procedure with the use of a minimum number of animals per step, sufficient information is obtained on the acute toxicity of the test item to enable its classification . The item is tested using a stepwise procedure with up to four fixed doses. Absence or presence of compound-related mortality of the animals dosed at one step will determine the next step.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

none

Body weight:

None of the animals showed weight loss during the observation period.

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

Other findings:

none

Any other information on results incl. tables

CLINICAL SIGNS PER STEP

Step 1: 3 females (1 -3) / 2000 mg/kg bw	no specific findings during the whole observation period
Step 2: 3 females (4 -6) / 2000 mg/kg bw	no specific findings during the whole observation period

PATHOLOGY

Step 1: 3 females (1 -3) / 2000 mg/kg bw	no specific findings
Step 2: 3 females (4 -6) / 2000 mg/kg bw	no specific findings

LD50 CUT-OFF

Dose [mg/kg bw]	No. of animals	No. of intercurrent deaths	LD50 Cut-Off
2000	6	0	not classified

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, a single oral application of the test item Methacryloyloxyethyl succinate to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.
The median lethal dose of Methacryloyloxyethyl succinate after a single oral administration to female rats, observed over aperiod of 14 days is:
LD50 cut-off (rat): unclassified
According to Annex I of Regulation (EC) 1272/2008 the test item Methacryloyloxyethyl succinate has no obligatory labelling requirement for toxicity and is not classified .
According to GHS (Globally Harmonized Classification System) the test item Methacryloyloxyethyl succinate has no obligatory labelling requirement for toxicity and is not classified.

Executive summary:

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was dissolved in the vehicle PEG 400 at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

- Step 1: Female 1 -3 / dose 2000 mg/kg bw / no intercurrent deaths

- Step 2: Female 4 -6 / dose 2000 mg/kg bw / no intercurrent deaths

All animals survived until the end of the study without showing any test-item related signs of toxicity.

Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain.

At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

On the basis of the test results and in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008, the substance should be: not classified.

On the basis of the test results and in conformity with the criteria given in GHS (Globally Harmonized System of Classification and Labelling of Chemicals), the substance should be: not classified.

Conclusion

Under the conditions of the present study, a single oral application of the test item Methacryloyloxyethyl succinate to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.

The median lethal dose of Methacryloyloxyethyl succinate after a single oral administration to female rats, observed over aperiod of 14 days is:

LD50 cut-off (rat): unclassified

According to Annex I of Regulation (EC) 1272/2008 the test item Methacryloyloxyethyl succinate has no obligatory labelling requirement for toxicity and is not classified .

According to GHS (Globally Harmonized Classification System) the test item Methacryloyloxyethyl succinate has no obligatory labelling requirement for toxicity and is not classified.