2-ethoxy-2-oxoethyl ethyl methylenemalonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 03/08/2018 to 08/11/2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

1-(2-ethoxy-2-oxoethyl) 3-ethyl 2-methylidenepropanedioate

EC Number:

817-217-9

Cas Number:

116280-23-0

Molecular formula:

C10H14O6

IUPAC Name:

1-(2-ethoxy-2-oxoethyl) 3-ethyl 2-methylidenepropanedioate

Test material form:

liquid

Details on test material:

- Purity: 98%
- Batch: MM212_S4
- Fabrication date: 18/07/2018
- Stabilizers:
7 ppm Methanesulfonic acid;
2000-3000 ppm 2,3,5-trimetilhidroquinona / Hydroquinone;
15 ppm Sulphuric acid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source (supplier): Envigo RMS Spain S.L.
- Age at study initiation: 8 weeks old
- Weight at study initiation: Mean: 221.6g
- Fasting period: Overnight before administration and approx. 3-4h afterwards
- Diet (food): Teklad global 14% protein rodent maintenance diets 2914C (irradiated).
- Food availability: Ad libitum except for an overnight fast prior to dosing and approx. 3-4h afterwards.
- Water: Tap water
- Water availability: Ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3ºC
- Humidity (%): 30-70%
- Light cycle: 12:12

IN-LIFE DATES: At the end of the 15-day observation period, all surviving animals were euthanized in a CO2 atmosphere.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

300 (starting dose) and 2000 mg/kg

No. of animals per sex per dose:

6 animals per dose 300 mg/kg (in two dose steps: Group A (3 animals) and Group B (3 animals))
6 animals per dose 2000 mg/kg (in two dose steps: Group C (3 animals) and Group D (3 animals))
Therefore:
Total number of animals: 12 animals to perform 4 dose steps (A, B, C and D)

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observahhtions: 30min, 2h and 4h post-administration and once daily thereafter during the 15-day observation period.
- Frequency of weighing: once during the acclimatisation period, immediately before administration for dosing purposes (from 3-4h fasted animals), weekly thereafter and prior to sacrifice.
- Necropsy of survivors performed: yes
Any visible clinical signs, discomfort and mortality were recorded.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Group A - (Step 1) 300 mg/kg: No mortality ocurred.
Group B - (Step 2) 300 mg/kg: No mortality ocurred.
Group C - (Step 3) 2000 mg/kg: No mortality ocurred.
Group D - (Step 4) 2000 mg/kg: No mortality ocurred.

Clinical signs:

other: Group A - (Step 1) 300 mg/kg: No abnormalities detected. Group B - (Step 2) 300 mg/kg: No abnormalities detected. Group C - (Step 3) 2000 mg/kg: No abnormalities detected. Group D - (Step 4) 2000 mg/kg: No abnormalities detected.

Gross pathology:

All animals killed at the end of the 15-day observation period.
Gross pathology observations: none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

At 2000mg/kg no mortality ocurred. Therefore, the oral median lethal dose (LD50) will be >2000 mg/kg (female rats).
Based on these results and according to the EU classification criteria outlined in Regulation 1272/2008 (CLP) the compound does not need to be classified.

Executive summary:

The objective of this study is to evaluate the acute oral toxicity of the test item in female Sprague-Dawley rats by the Acute Toxic Class Method (OECD guideline Nº 423).

6 female Sprague-Dawley rats were treated with test item by oral gavage administration at 300 mg/kg bw (starting dose) and other 6 at 2000 mg/kg bw. The rats were observed for 15 days.

At 300 and 2000 mg/kg bw, no mortality ocurred and no abnormalities were detected. Therefore, the oral median lethal dose (LD50) will be >2000 mg/kg (female rats).

Based on these results and according to the EU classification criteria outlined in Regulation 1272/2008 (CLP) the compound does not need to be classified.