reaction mass of diethyl (E)-2-methylbut-2-enedioate and diethyl (Z)-2-methylbut-2-enedioate

Endpoint summary

Description of key information

Acute toxicity: oral

The LD50 value of the test item was determined to be higher than 2000 mg/kg bw after single oral administration in female rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 September 2017 - 7 November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 weeks old
- Weight at study initiation: 162.8−182.5 g
- Fasting period before study: fasted overnight, approximately 16 hours prior to dosing
- Housing: Stainless wire mesh cage, 260W×350D×210H (mm), one animal/cage
- Diet: Pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C), ad libitum
- Water: public tap water, filtered and irradiated by ultraviolet light, ad libitum
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 23.0
- Humidity (%): 46.0 - 58.3
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 60 and 400 mg/mL
- Amount of vehicle: 5 mL/kg bw
- Justification for choice of vehicle: as a result of the vehicle review, due to solubility
- Lot/batch no.: MKCC0462 (SIGMA-ALDRICH)

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose level (300 mg/kg) for this study was selected because there was no available toxicity information on the test substance.

Doses:

Step 1 and Step 2: 300 mg/kg bw, Step 3 and Step 4: 2000 mg/kg bw

No. of animals per sex per dose:

3 females per step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: frequently during Day 0, daily thereafter; weighing: Day 0, 1, 3 and 7
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths of animals at 300 and 2000 mg/kg bw throughout the study.

Clinical signs:

No abnormalities of clinical signs were observed in any animal at 300 and 2000 mg/kg bw throughout the study.

Body weight:

A decrease in the body weight was observed in one animal at 300 mg/kg bwon Day 3. Then, normal body weight gain was observed in this animal from Day 7. It was not considered to be a test substance-related effect because there were no clinical signs or necropsy findings of morphologic abnormalities.
Normal body weight gain was observed in all animals at 2000 mg/kg bw throughout the study.

Gross pathology:

No grossly visible findings were observed in any animal at 300 and 2000 mg/kg bw.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of the test item was determined to be higher than 2000 mg/kg bw after single oral administration in female rats.

Executive summary:

The purpose of this study was to assess the potential toxicity of the test item following a single oral dose administration to female Sprague-Dawley rats. Four dose groups of three females were utilized. In Step 1 and Step 2 a dose of 300 mg/kg bw was administered and in Step 3 and Step 4 a dose of 2000 mg/kg bw. All animals were monitored for clinical signs and body weight changes during the 14-day observation period after administration. They were subjected to a gross necropsy at the end of the observation period.

There were no deaths of animals at 300 and 2000 mg/kg bw. No test substance-related effects were observed in clinical signs, body weight data or necropsy findings in any animal at 300 and 2000 mg/kg bw.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the The LD50 value of the test item was determined to be > 2000 mg/kg bw and the LD50cut off  was determined to be ≥ 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral

The purpose of this study was to assess the potential toxicity of the test item following a single oral dose administration to female Sprague-Dawley rats. Four dose groups of three females were utilized. In Step 1 and Step 2 a dose of 300 mg/kg bw was administered and in Step 3 and Step 4 a dose of 2000 mg/kg bw. All animals were monitored for clinical signs and body weight changes during the 14-day observation period after administration. They were subjected to a gross necropsy at the end of the observation period.

There were no deaths of animals at 300 and 2000 mg/kg bw. No test substance-related effects were observed in clinical signs, body weight data or necropsy findings in any animal at 300 and 2000 mg/kg bw.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, theThe LD50 value of the test item was determined to be > 2000 mg/kg bw and the LD50 cut off  was determined to be ≥ 5000 mg/kg bw.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on this data, the substance is not considered not to be classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.