N,N,N',N'-tetramethylethylenediamine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

23 September to 23 October 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was performed to determine the potential for Bulab 600 to produce toxicity from a single 1-hour inhalation exposure.

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethylethylenediamine

EC Number:

203-744-6

EC Name:

N,N,N',N'-tetramethylethylenediamine

Cas Number:

110-18-9

Molecular formula:

C6H16N2

IUPAC Name:

[2-(dimethylamino)ethyl]dimethylamine

Test material form:

liquid

Details on test material:

clear, colourless to pale yellow

Specific details on test material used for the study:

Bulab 600
Lot 0-5201

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Charles River Breeding Laboratories
Housing: Individually housed
Temperature controlled
Food: Purina rat chow, ad libitum except during exposure
Water: Madison city well water, ad libitum except during exposure
Age at experimental start: 8 weeks
Weight at experimental start: 158-240 g
Acclimatisation period: 7 days

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Remark on MMAD/GSD:

Particle size not measured.

Details on inhalation exposure:

The initial screen level was conducted at a nominal concentration of 69100 mg/m^3 of air for 1 hour and the second level at 17900 mg/m^3 of air for 1 hour. The time for equilibration (90% of desired concentration) was 14 minutes for 69.1 mg/L of air and 8 minutes for 17.9 mg/L of air thereby the exposure time was 74 and 68 minutes, respectively. Administration of the test material was during only the initial 60 minutes. The test exposures were conducted with samples of the test material in which each contained the same concentration of formulated ingredients. The test material was administered directly into the chamber using the Spraying Systems unit which was equilibrated prior to conducting the exposure by running the unit and calculating the dispersion rate several times. The unit was checked for variation in the rate of dispersion periodically during the exposure period. Exposures were conducted in an 842 L stainless steel semi-portable exposure chamber which was equipped with an exhaust port which was connected to an exhaust fan, providing an adjustable air flow through the chamber. Air flow was determined by a calibrated pressure gauge which measured the pressure drop across a defined inlet orifice. The test material was administered into the chamber near the junction for the air inlet pot, which allows the test material and incoming air to mix evenly within the chamber at the top before being drawn down over the animals.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

1 h

Remarks on duration:

Equilibration time was 14 minutes for high dose and 8 minutes for low dose

Concentrations:

17900 and 69100 mg/m^3 of air for 1 hour, equivalent to 17.9 and 69.1 mg/L of air

No. of animals per sex per dose:

Five

Control animals:

yes

Details on study design:

Animal observations were recorded periodically during exposure. Immediately following and up to 1 hour after exposure to the compound, the animals were observed for pharmacotoxic signs and mortality. Thereafter, the animals were observed daily for 14 days for pharmacotoxic effects and mortality. Body weights for all animals were taken just prior to compound exposure and again at 7 and 14 days post exposure for survivors. Animals were sacrificed at 14 days. They were subjected to a gross necropsy examination and abnormalities were recorded.

Statistics:

Not required.

Results and discussion

Preliminary study:

Not performed

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 17 900 - < 69 100 mg/m³ air

Based on:

test mat.

Exp. duration:

1 h

Mortality:

All animals died at 69100 mg/m3. No mortalities were observed at 17900 mg/m3 or for the control group.

Clinical signs:

other: In the control group, animals appeared normal through the exposure and post dose observation periods. In the low exposure concentration group (17.9 mg/L), shallow breathing, gasping, lacrimation, nasal discharge, oral discharge, red and irritated eyes we

Body weight:

Body weights were recorded, but body weight gain was not discussed in the report.

Gross pathology:

In the control group, the lungs of one female contained multiple (pinpoint to 2 mm) red foci, considered to be an incidental finding. There were no other gross lesions in the remaining nine animals. In the low dose group (17.9 mg/L), a focal (1-2mm) pale, opaque, firm, raised papule was observed on central corneas of each left eye of three males and one female and bilaterally in two females. The central corneas of another female contained a 4 mm, red and white, firm raised papule. Both kidneys of the fifth female contained moderate pelvic dilation which was considered to be incidental. In the high dose group (69 mg/L), there was darkening of the liver in two males and five females. Corneal opacity of the right eye of one male was observed. Mild hydrometra was observed in the uterus of one female, which was considered to be incidental. Two rats exhibited no significant gross lesions.

Any other information on results incl. tables

No futher information available.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The acute inhalation LC50 was between 17.9 and 69.1 mg/L for a 1-hour exposure. Using Haber's law (LC50 * 1h/4h), this equates to a 4-hour LC50 of between 4.5-17.3 mg/L. However there was no analytical verification of the achieved concentration and no measurement of particle size, therefore the actual exposure concentrations are unknown.

Executive summary:

In an acute inhalation toxicity study conducted with the substance TMEDA (Bulab 600), a group of Sprague Dawley rats (5/sex) was exposed to atmospheres containing nominal concentrations of 17900 or 69100 mg/m3 for 1 hour following equilibration. A control group was also tested. All animals exposed to 69100 mg/m3 died; however no mortalities were observed at 17900 mg/m3 or for the control group. In the low exposure group, shallow breathing, gasping, lacrimation, nasal discharge, oral discharge, red and irritated eyes were observed during the exposure period. During the 14-day observation period, the animals showed laboured breathing, nasal discharge, vasodilation and corneal changes. At necropsy, raised papules were observed on the corneas of seven animals. In the high exposure group (69 mg/L), laboured breathing, nasal discharge, convulsions and irritated eyes were observed prior to death. At necropsy, darkening of the liver was reported for two males and five females. Corneal opacity was observed in one animal. Two rats exhibited no significant gross lesions. The acute inhalation LC50 was between 17.9 and 69.1 mg/L for a 1-hour exposure.  Using Haber's law, this equates to a 4-hour LC50 of between 4.5-17.3 mg/L (LC50 * 1h/4h).  However there was no analytical verification of the achieved concentration and no measurement of particle size, therefore the actual exposure concentrations are unknown.