Trimethylamine, N-oxide

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:

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

Data source

Reference

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)

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test:
2 groups of 6 male Crl:CD(SD)BR rats were exposed for single, 4h periods. The rats were observed and weighed daily for 14 d, at which time the surviving rats were sacrificed (without pathologic examination).

GLP compliance:

not specified

Test type:

fixed concentration procedure

Limit test:

no

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

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: supplied by the Chemicals and Pigments Department, E. I. du Pont de Nemours and Company, Inc., Belle, W.V.
- Impurities: 0.06% dimethylamine, 0.01 % monomethylamine, and 0.17% water
- Expiration date of the lot/batch: no data
- Purity test date: no data

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratory, Kingston, N.Y.
- Age at study initiation: 7-8 wk old
- Weight at study initiation: between 234 and 293 g
- Fasting period before study: not specified
- Housing: in 8 x 14 x 8 in. suspended, steel-mesh cages
- Diet: Purina Certified Rodent Chow 5002 ad libitum
- Water: ad libitum
- Acclimation period: quarantined for 1 wk prior to testing

ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 2°C
- Humidity: 50 ± 10%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): timer-controlled 12/12-h light/dark cycle.

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
no additional information

TEST ATMOSPHERE
no analysis

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

2000 ppm and 3500 ppm

No. of animals per sex per dose:

six males per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no

Statistics:

not applicable

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC0

Effect level:

2 000 ppm

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 3 500 ppm

Based on:

test mat.

Exp. duration:

4 h

Mortality:

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.
Surviving rats showed 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 post exposure period.

Clinical signs:

other: During exposure, all rats showed labored breathing, nasal and oral discharges, and neither moved nor responded to sound.

Body weight:

Surviving rats showed moderate to severe weight losses 1-2 d post exposure.

Gross pathology:

not examined

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

A 4-hour LC50 (gas) of ca. 8.58 mg/L was determined (equivalent to 3500 ppm).

Executive summary:

In an acute inhalation study, 2 groups of 6 male Crl:CD(SD)BR rats were exposed for single, 4h periods. The tested concentrations were 2000 ppm and 3500 ppm The rats were observed and weighed daily for 14 d, at which time the surviving rats were sacrificed (without pathologic examination).

No deaths occurred following a 4h exposure to 2000 ppm TMA whereas 3 of 6 rats exposed to 3500 ppm died during the exposure period. During exposure, all rats showed labored 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.