N,N-bis(1-methylethyl)formamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 02, 2021to March 19, 2021

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

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:

N,N-bis(1-methylethyl)formamide

EC Number:

220-284-1

EC Name:

N,N-bis(1-methylethyl)formamide

Cas Number:

2700-30-3

Molecular formula:

C7H15NO

IUPAC Name:

N,N-Diisopropylformamide

Specific details on test material used for the study:

Batch No.: M-O303190723301F
Purity: 99.68%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: SPF(Beijing) Biotechnology Co., Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable)
- Age at study initiation: 51-60 days on arrival, in the range of 57-70 days at the commencement of each animal’s dosing.
- Weight at study initiation: The body weight range was 231-241 g at grouping
- Fasting period before study: overnight prior to dosing
- Housing: Animals were housed in Room D130 of the facility’s barrier system. Animals were raised in suspended, stainless steel cages. Animals were housed in groups during the adaption period. Animals were housed individually during the test.
- Historical data:
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
- Microbiological status when known
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3-22.2
- Humidity (%): 50%-68%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30, 5 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: because the test item has no solubility and hydrolysis information according to the MSDS provided by sponsor, to prevent its hydrolysis in water, corn oil was used as the vehicle.
- Lot/batch no. (if required): 20201204
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): For the purpose of 300 and 50 mg/kg b.w. dose level, the test item was freshly prepared with the vehicle. Calculated the theoretical amounts of test item and weighed it in a grinding jar. Put a small amount of vehicle into the grinding jar, and then stirred with a glass rod, and subsequently diluted the test item with vehicle to the scale mark. The prepared formulations were fully stirred and labeled for use.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: According to OECD Guideline for Testing of Chemicals “Acute Oral Toxicity-Acute Toxic Class Method” (TG 423, adopted 2001) and the dose level of 300 mg/kg b.w. is selected as the starting dose from one of four fixed dose levels (5, 50, 300, 2000 mg/kg)

Doses:

300 and 50 mg/kg b.w.

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Inspections were made twice daily, in the morning and afternoon, during normal working days (except that it was made once on the dosing and necropsy days), and once daily at weekends and public holiday. Clinical observations were performed once during the first 30 minutes and at 1, 2 and 4 hours after application approximately, and then once each day for up to 14 days. Individual weights of animals were determined within 24 hours after arrival, at the end of adaption period , at grouping (the day before each animal's dosing day), on Day 0 (day of dosing), Day 7 and Day 14. Dead animals were weighed during the test.
- Necropsy of survivors performed: Animals surviving to the end of the study were anesthetized by CO2 and bled by abdominal aorta to death. A gross necropsy was performed on all animals under test. The necropsy included carefully eye examinations of the abdominal, thoracic organs and their contents of all animals.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

Dose Level-The first dosing (300 mg/kg b.w.): All animals dead.
Dose Level-The second dosing (50 mg/kg b.w.): There were no deaths or moribund status of any of the animals during the test.
Dose Level-The third dosing (50 mg/kg b.w.): There were no deaths or moribund status of any of the animals during the test.

Clinical signs:

Dose Level-The first dosing (300 mg/kg b.w.): All animals showed jump, blood discharge of mouth, tachypnea and dead after administration.
Dose Level-The second dosing (50 mg/kg b.w.): All animals showed no abnormal symptoms during the test.
Dose Level-The third dosing (50 mg/kg b.w.): All animals showed no abnormal symptoms during the test.

Body weight:

All of the surviving animals gained body weights during the test.

Gross pathology:

All animals under test showed no abnormalities at necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 in rats for the test item was estimated to be between 300 and 50 mg/kg b.w. and the cut-off value of LD50 was estimated to be 200 mg/kg b.w.

Executive summary:

The study was performed to assess the acute oral toxicity of the test item in Sprague Dawley rats. The method was designed to meet the OECD Guideline 423 under GLP.

The acute oral LD50 in rats for the test item was estimated to be between 300 and 50 mg/kg b.w. and the cut-off value of LD50 was estimated to be 200 mg/kg b.w.