Trimethylamine

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Nasal Irritation and Pulmonary Toxicity of Aliphatic Amines in Mice.

Author:

Gagnaire.,F. Azim S., Bonnet P., Simon P., Guenier J.P.and de Ceaurriz J.

Year:

1989

Bibliographic source:

Journal of applied Toxicology, Vo.9(5), 301-304 (1989).

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Mice were exposed (nose-only) to TMA by inhalation to measure a decrease in respiratory rate (RD50)as well as to determine pulmonary toxicity. The breathing frequency was used as an index of upper respiratory tract irritation.

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

respiratory irritation

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:

- Name of test material (as cited in study report): trimethylamine
- Substance type:liquid or as a solution of the gaseous amine in water
- Analytical purity: high purity

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:IFFA CREDO, Domaine des Oncins, Saint Germain sur l'Arbresle
- Weight at study initiation: 20-25 g
- Diet (e.g. ad libitum): UAR-Alimentation, Villemoisson ad libitum
- Water (e.g. ad libitum): tab water ad libitum
- Acclimation period: 1 day
- Inhalationchamber: 200 L stainless-steel with adjustable airflow (10-30 m3/h), negative pressure to prevent leakage of test atmosphere
(additional airflow bubbled through the liquid amines and the vaporized compounds were diluted with air to the required concentration before entering the exposure chamber)

Administration / exposure

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Remarks:

exposed via tracheal cannulation

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

15 min

Frequency of treatment:

single exposure

Post exposure period:

not applicable
(75 min (in pulmonary toxicity test))

Doses / concentrations

Remarks:

Doses / Concentrations: 4 to 6 different exposure concentrations, range 17-70 ppm
Basis: nominal conc.

No. of animals per sex per dose:

6

Control animals:

no

Results and discussion

Details on results:

RD 50 = 61 ppm, 95 % confidence interval (ppm), tentative standard on the basis of 0.1 RD 50 < 5
No lethal effect at the highest test concentration (169 mg/m³).

Any other information on results incl. tables

For all amines, except for allylamine and diallylamine, the onset of action was very rapid, ca. 30 s to 1 min. For both of the amines previously mentioned, the effect became maximal after 10-15 min of exposure. At the end of a 15-min exposure period, the recovery of respiratory frequencies to the pre-exposure values was also rapid, ca. 1 min.

The effects were slower to develop than in non-cannulated mice, the maximal effects being obtained after 120 min of exposure. After the end of exposure there was incomplete, if any, recovery, especially for the highest concentrations.

Applicant's summary and conclusion

Conclusions:

Trimethylamine is iriitating to the respriatory tract. In concentrations of 61 ppm (= 147 mg/m³ air) a 50 % decrease of the respiratory rate in rats was found.

Executive summary:

Gagnaire et.al. performed a RD50 test, based on depression of respiratory rate in nose-only exposed mice (Gagnaire et al., 1989). 6 male mouse (Swiss OF1 (IFFA CREDO)) were exposed for 15 minutes to trimethylamine.

As result a RD50 of 147 mg/m3 air was reported. No lethal effect was observed at highest test concentration of 169 mg/m3.

Previous studies with several chemicals have shown that the RD50 (50% decrease in the respiratory rate) values can be used successfully to predict safe industrial exposure. At 0.1 RD50, humans would experience some slight discomfort and this should be the highest level permitted in industry. At 0.01 RD50 no sensory irritation is observed and a convenient threshold limit value (TLV) would be 0.3 RD50 the midpoint on a logarithmic scale between the. 0.1 and 0.01 RD50. The present data show that, for seven amines out of ten compounds for which TLVs exist, the current TLVs are always < 0.1 RD50 but higher than 0.01 RD50. For dimethylamine, trimethylamine and cyclohexylamine, a TLV of 10 ppm seems too high and should be divided by a factor of two.

The differences between RD50 and RD50TC (RD50 in tracheally cannulated mice) indicate that amines are essentially irritants for upper airways. While the respiratory rate responses of oronasally exposed mice indicative of nasal irritation set in rapidly and were reversible when exposure to the irritants ceased, the respiratory rate responses of cannulated mice were slower to develop than in oronasally exposed mice, and no, or incomplete, recovery was observed after the end of exposure, when mice were allowed to breath fresh air.