N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-01-31 to 1997-02-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

This experiment was performed in accordance with OECD 401 without deviations. A few minor details were not described in the report (randomization of animals and assignment to treatment group, weight variation among animals at study initiation, etc.) but all report elements required by the guideline were present. Further, a dose response relationship was established via this experiment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

EC Number:

221-220-5

EC Name:

N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Cas Number:

3033-62-3

Molecular formula:

C8H20N2O

IUPAC Name:

{2-[2-(dimethylamino)ethoxy]ethyl}dimethylamine

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): A-99
- Physical state: Liquid
- Analytical purity: 99.2%
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: N/A
- Isomers composition: N/A
- Purity test date: 1997-03-12
- Expiration date of the lot/batch: No data
- Storage condition of test material: Original container at room temperature
- Other: A sufficient amount of test material was transferred from the original container to a labeled storage vessel. A stir bar was added, and the test material was maintained on a magnetic stir plate throughout the dosing procedures.
- Lot/batch No.: T208121896

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, MI
- Age at study initiation: N/A (Young adult)
- Weight at study initiation: 206 to 259 grams at initiation of dosing
- Fasting period before study: Approximately 18-20 hours prior to dosing
- Housing: Individual wire mesh cages
- Diet (e.g. ad libitum): PMI Feeds, Inc. Certified Rodent LabDiet 5002 was provided ad libitum
- Water (e.g. ad libitum): Municipal water was provided ad libitum
- Acclimation period: Minimum of 7 days prior to initiation of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.06 to 22.84
- Humidity (%): 35.9 to 46.7
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Substance used neat
- Amount of vehicle (if gavage): Substance used neat
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 1.22 mL/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Dose range-finding studies

Doses:

500, 720 and 1037 mg/kg (0.59, 0.85 and 1.22 mL/kg, respectively)

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality at approximately 1.0, 3.0 and 4.0 hours post dosing on day 0 and twice daily (morning and afternoon) thereafter for 14 days; clinical observations at approximately 1.0, 3.0 and 4.0 hours post dosing on day 0 and once daily thereafter for 14 days; Body weights at days -1, 0 (initiation), 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: None

Statistics:

Litchfield and Wilcoxon

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

708 mg/kg bw

Based on:

test mat.

95% CL:

652 - 769

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

603 mg/kg bw

Based on:

test mat.

95% CL:

527 - 689

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

677 mg/kg bw

Based on:

test mat.

95% CL:

636 - 722

Mortality:

At the 500 mg/kg dose level, 0/5 males and 0/5 females died. At the 720 mg/kg dose level, 3/5 males and 5/5 females died. At the 1037 mg/kg dose level, 5/5 males and 5/5 females died. The majority of deaths (17/18) occurred between days 0-2. One male in the 720 mg/kg group died on day 8.

Clinical signs:

other: Clinical findings were noted in all dose groups. Wet and/or dried red, yellow and/or clear staining/matting/material (around the nose, mouth, eye(s), forepaw(s) and/or urogenital area) was noted for 23 rats. Nineteen animals were hypoactive. Rales and

Gross pathology:

Of the animals found dead, 17/18 animals had gastrointestinal abnormalities (a distended stomach, red fluid and/or dark red contents, reddened mucosa, dark red area(s) in the intestine and/or stomach). Small seminal vesicles, a hemorrhagic thymus gland and dilated renal pelvis were noted for one male rat each. Seven animals had various external matting (yellow, red and/or brown matting around the eyes, nose, mouth, urogenital and/or anogenital area). There were no other gross necropsy findings for all other animals found dead. There were no findings for animals which survived to the scheduled necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test substance was found to be 677 mg/kg with 95% confidence limits of 636-722 mg/kg when administered once orally via gastric intubation to fasted male and female albino rats. Based on these results and according to the CLP Regulation, the test substance is to be classified as acute oral toxicant category 4.