Dibutylamine

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:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dibutylamine

EC Number:

203-921-8

EC Name:

Dibutylamine

Cas Number:

111-92-2

Molecular formula:

C8H19N

IUPAC Name:

N-butylbutan-1-amine

Details on test material:

Di-n-butylamine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Margate, Kent, England
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 200g
- Fasting period before study: no except during exposure
- Housing: 5 animals of the same sex per cage
- Diet (e.g. ad libitum): ad libitum (Labsure LAD1)
- Water (e.g. ad libitum): ad libitum tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-43

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The test substance was supplied to an atomiser in the generator from a syringe driven at a constant rate by a syringe pump.
The compressed air supply to the generator was dried, filtered and oil-free.

The chamber was made of Perspex and had an internal volume of approx. 130l.
The chamber was divided by wire mesh partitions to provide 10 separate animal compartments.

A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 0.03-0.06 ml/min. An in-line flow meter was used to monitor airflow throughout the exposure.

A syringe filled with dibutylamine was fitted to the syringe pump and connected to the generator with PTFE tubing. The flow rate was set at 0.18ml/min.

After 4 hours exposure, the supply of the test substance was discontinued and the exposure chamber was allowed to clear before rats were removed for examination.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Five air samples were taken from the chamber during the exposure to determine to concentration of dibutylamine in gas chromatography.

Duration of exposure:

4 h

Concentrations:

0.76, 1.08, 1.18, 1.39, 3.91 mg/l

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily until 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:
clinical signs: continuously during exposure and twice daily until the observation period
body weight: daily
organ weights: lungs

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

218 ppm

Exp. duration:

4 h

Remarks on result:

other: equivalent to 1,15 mg/l

Mortality:

Deaths occurred during exposure to the test substance at 1.39 mg/l or at 3.91 mg/l (see table 1).

Clinical signs:

other: During exposure The signs seen in rats exposed to the test substance were considered to be due to the irritant nature of the vapour. The signs evident in exposed rats included closing or partial closing of the eyes, reduced respiratory rate, abnormal resp

Body weight:

The rats surviving exposure to the test substance lost weight or had a reduced rate of bodyweight gain for up to 2 days following exposure. Subsequently, the rate of bodyweight gain was similar to control rats.

Gross pathology:

Lungs of rats that died were congested. A viscous fluid was found in the trachea of 2 deceased rats in group 1.18 mg/l.

Other findings:

The lung weights of the majority of the rats that died following exposure were higher than normal.
The lung weights for rats that survived were within normal limits.

Any other information on results incl. tables

Table 1: Mortality after test substance treatment

	Mortality (Nb dead/Nb exposed)
Concentration in air (mg/l)	Male	Female	Total
Control	0/5	0/5	0/10
Control	0/5	0/5	0/10
3,91	5/5	5/5	10/10
1,39	5/5	5/5	10/10
1,18	3/5	1/5	4/10
1,08	0/5	0/5	0/10
0,76	2/5	0/5	2/10

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The LC50 value of the test substance after vapour inhalation for 4h was found to be 218 ppm (equivalent to 1,15 mg/l) in rats.

Executive summary:

In an acute toxicity inhalation study, male and female rats (Sprague-Dawley) were treated with the vapour of the test substance for 4h. 5 animals per sex per concentration (0.76, 1.08, 1.18, 1.39, 3.91 mg/l)

and no vehicle were used.

Deaths occurred during exposure to the test substance at 1.39 mg/l or at 3.91 mg/l. The signs seen in rats exposed to the test substance were considered to be due to the irritant nature of the vapour. The signs evident in exposed rats included closing or partial closing of the eyes, reduced respiratory rate, abnormal respiratory movements and adoption of an anormal body posture. Gasping, exessive salivation, lacrimation, and convulsions were observed less frequently.

After the removal from the test chamber, rats exposed to the test substance showed abnormal breathing, lethargy, ataxia, prone posture and intermittent convulsions.

Clinical signs evident for 2 days following exposure included abnormal breathing, rales, brown staining or yellow staining in the urogenital area and sneezing.

With the exception of 1 female rat with damaged tail all rats surviving exposure to the test substance were of normal appearance and behaviour by day 3 of the observation period.

 The rats surviving exposure to the test substance lost weight or had a reduced rate of bodyweight gain for up to 2 days following exposure. Subsequently, the rat of bodyweight gain was similar to control rats.

 Lungs of rats that died were congested. A viscous fluid was found in the trachea of 2 deceased rats in group 1.18 mg/l. The lung weights of the majority of the rats that died following exposure were higher than normal. The lung weights for rats that survived were within normal limits.

The LC50 value of the test substance was found to be 218 ppm (equivalent to 1,15 mg/l) in rats.