Trimethylamine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well-documented publication, which meets basic scientific principles

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Inhalation Toxicology of Trimethylamine

Author:

Kinney L.A., Burgess, B. A., Chen, H. C. and Kennedy, G. L.

Year:

1990

Bibliographic source:

Inhalation Toxicology, 2, 41-51, (1990)

Reference 2

Reference Type:

publication

Title:

No information

Author:

Kinney L.A. et al.

Year:

1984

Bibliographic source:

The Toxicologist 4, 68, (1984), Abstract

Materials and methods

Principles of method if other than guideline:

The need to more accurately determine both the qualitative and quantitative response to inhaled TMA prompted this investigation, in which they looked at the response of rats to inhaled TMA following both single and repeated exposures. No details on the principle of method used is given.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Trimethylamine

EC Number:

200-875-0

EC Name:

Trimethylamine

Cas Number:

75-50-3

Molecular formula:

C3H9N

IUPAC Name:

N,N-dimethylmethanamine

Details on test material:

Trimethylamine, purity 99.76 %

Specific details on test material used for the study:

Trimethylamine (TMA, CAS no. 75-50-3)

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

male Crl:CD(SD)BR rats

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS - male Crl:CD(SD)BR rats
- Source: Charles River Breeding Laboratory, Kingston, N.Y.
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Age at study initiation: 7-8 wk old
- Weight at study initiation: weighing between 234 and 293 g
- Fasting period before study: not specified
- Housing: in 8 x 14 x 8 in. suspended, steel-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow 5002 ab libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: quarantined for 1 wk prior to testing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%): 50 ± 10%
- Air changes (per hr): nto specified
- Photoperiod (hrs dark / hrs light): timer-controlled 12/12-h light/dark cycle.

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Remarks:

Animals were placed in cylindrical stainless-steel holders equipped with conical nose pieces. The restrainers were inserted into face plates on the exposure chambers such that the nose of each rat protruded into the chamber.

Vehicle:

air

Details on inhalation exposure:

Animals were placed in cylindrical stainless-steel holders equipped with conical nose pieces. The restrainers were inserted into face plates on the exposure chambers such that the nose of each rat protruded into the chamber.
Atmosphere Generation: Caseous atmospheres of TMA were generated by dilution of pure TMA with air. Polyethylene gas sample bags were filled with TMA, and the gases were subsequently metered into a three-neck mixing flask with FMI (Fluid Metering Inc., Oyster Bay, N.Y) metering pumps. The pumps were chosen with capacities sufficient to produce the design concentrations of 75, 250, and 750 ppm when mixed with 15 L/min of dilution air. The diluted gases were directed into 20-L cylindrical glass exposure chambers.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Analyical verification in 30-min intervals during the exposures, by pumping air continuously into Miran model 1A infrared spectrometers at a flow rate of 5 L/min and analysis at 3.3 µm and comparison freshly prepared TMA standards.

Duration of exposure:

4 h

Concentrations:

2000 ppm
3500 ppm

No. of animals per sex per dose:

6 males per group

Details on study design:

- Duration of observation period following administration: 14 days (The rats were observed and weighed daily for 14 d, at which time the surviving rats were sacrificed (without pathologic examination).
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

8.6 mg/L air

Exp. duration:

4 h

Remarks on result:

other: given in original study as 3500 ppm

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

3 500 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 3 of 6 rats exposed to 3500 ppm died during the exposure period

Remarks:

.

Effect levels 3

Sex:

male

Dose descriptor:

LC0

Effect level:

2 000 ppm

Remarks on result:

other: No death occurred following a 4-h exposure to 2000 ppm TMA

Remarks:

.

Mortality:

No deaths occurred following a 4-h exposure to 2000 ppm TMA;
3 of 6 rats exposed to 3500 ppm died during the exposure period

Clinical signs:

other: During exposure, all rats showed labored breathing, nasal and oral discharges, and neither moved nor responded to sound. Rats exposed to 3500 ppm also had dry red nasal and ocular discharge during the early stages of the postexposure period.

Body weight:

Surviving rats showed moderate to severe weight losses 1-2 d postexposure and lung noise from 1 to 9 d postexposure.

Gross pathology:

not performed

Any other information on results incl. tables

Acute Toxicity Study

In the acute experiment, no deaths occurred following a 4-h exposure to 2000 ppm TMA whereas 3 of 6 rats exposed to 3500 ppm died during the exposure period. During exposure, all rats showed laboured breathing, nasal and oral discharges, and neither moved nor responded to sound. Surviving rats showed moderate to severe weight losses 1-2 d postexposure and lung noise from 1 to 9 d postexposure. Rats exposed to 3500 ppm also had dry red nasal and ocular discharge during the early stages of the postexposure period.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

A LC50 (4 hours) of ca. 8.6 mg/L was determined (equivalent to 3500 ppm).

Executive summary:

Trimethylamine (TMA) is a pungent gas that occurs in nature and has many industrial applications, including use as an intermediate in the manufacture of many chemicals. The lowest lethal concentration following a single 4-h inhalation exposure was determined to be 3500 ppm. Croups of 10 male rats each were then exposed by nose-only inhalation 6 h/d, 5 d/wk for 2 wk to either 0 (control), 75, 250, or 750 ppm TMA. Rats were sacrificed either immediately following exposure or following a 14-d recovery period. Parameters investigated included in-life observations and body weights, clinical pathology, and histopathology with organ weights. Exposure to 750 ppm produced a decreased rate of weight gain in rats. Evidence of mild, reversible, polycytnemia was also seen in these rats. Effects of TMA were present in the nose, trachea, and lungs. Degenerative changes in the nose were reversible at 75 ppm, but not at 250 or 750 ppm. Mild emphysematous alveoli were seen in lungs of rats exposed to 750 ppm immediately following the exposures, but not after a recovery period. A no-observed-effect level for TMA under these test conditions was not determined, although the nasal effects seen at 75 nnm were minimal.