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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-07-12 to 2006-11-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study under GLP - however, only 1 dose level was tested.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Only 1 dose level

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

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): Bis-(2-Dimethylaminoethyl)ether; BDMAEE
- Physical state: Liquid
- Stability under test conditions: Stable under proper storage conditions
- Storage condition of test material: The test item was stored protected from sunlight, at room temperature (accepted range of 15-25 degrees C).
- Analytical purity: >97%
- Lot/batch No.: Batch Number H53261MIA
- Expiration date of the lot/batch: February 2008

Test animals

Species:

rat

Strain:

other: HanRcc:WIST(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Laboratory Animal Services, CH-4414 Fullinsdorf, Switzerland
- Age at study initiation: Males- 8 weeks; Females- 9 weeks
- Housing: Animals of the same sex were housed in groups of up to 5 in Makrolon type-IV cages with wire mesh tops and standard softwood bedding.
- Diet (e.g. ad libitum): Pelleted standard Kliba-Nafag 3433 rat maintenance diet, Batch No. 23/06 ad libitum except during the period when they were restrained in exposure tubes.
- Water (e.g. ad libitum): Community tap water from Fullinsdorf (chlorinated to approximately 0.5 ppm) ad libitum except during the period when they were restrained in exposure tubes.
- Acclimation period: 12 to 16 JUL 2006 under laboratory conditions, after clinical health examination


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours artificial fluorescent light.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only, flow-past exposure
- Exposure chamber volume: 2 liters
- Method of holding animals in test chamber: Restraint tubes positioned radially around the exposure chamber
- Source and rate of air: generated in ambient conditions using a Hospitak nebulizer at 12L/minute; airflow rate of test atmosphere as it arrived at the animal ports was 1.0 L/min/animal port.
- Temperature, humidity, pressure in air chamber: 20.9 degrees C, 1.7% relative humidity

TEST ATMOSPHERE
- Brief description of analytical method used: Samples collected 4 times during exposure and analyzed by gas chromatography with FID detection using the test item as reference.

CLASS METHOD
- Rationale for the selection of the starting concentration: Starting concentration was determined in agreement with the Sponsor based on previous studies which gave conflicting results at a EU classification cut off.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

2.242 mg/L (nominal); 2.204 mg/L (analytical mean)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality was checked once daily during acclimatization; once before exposure on the day of exposure; once per hour during exposure; once after exposure on the day of exposure; and twice daily during the observation period. A clinical examination was performed once per hour during exposure, once after exposure on the day of exposure, and once daily thereafter. Body weights were taken on test days 1 (before exposure), 4, 8, and 15 (the day of necropsy).
- Necropsy of survivors performed: yes
- Other examinations performed: mortality, clinical signs (changes in behavior, somatomotor activity, body position, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, e.g. tremors or convulsions, reactivity to handling or sensory stimuli, altered strength, alteration of the skin, fur, nose, eyes and mucous membranes), body weight

Statistics:

The LOGIT-Model was not used as only one group was exposed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.204 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

Due to poor health, male number 3 was sent to be sacrificed and necropsied on test day 5. The animal was in moribund condition and died in the pathology unit prior to sacrifice. All other animals were sacrificed as planned.

Clinical signs:

other: During and/or after the inhalation exposure the following findings were recorded in all animals: salivation, decreased spontaneous activity, breath sounds [rales], labored respiration, ruffled fur, and scabbed wound (nose). All these signs were observed u

Body weight:

Transient body weight loss was evident in all animals over the first three days following the inhalation exposure (test days 1 to 4), and was attributed to the treatment with the test item. All surviving animals of both genders showed body weight gain within the normal range during the rest of the observation period. Body weight of the animal dying prematurely was not recorded at necropsy.

Gross pathology:

No findings noted

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LC50 of the test substance for acute inhalation exposure (approximately 4 hours) in male and female rats observed for a period of 15 days obtained in this study was estimated to be greater than 2.204 mg/L.
Based on the results and according to the CLP Regulation, the test substance is classified as acute inhalation toxicant category 4.