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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1993

Materials and methods

Principles of method if other than guideline:
Method: other: RD50 determination
GLP compliance:
not specified
Test type:
other: determination of airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50)

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1,3,3-tetramethylbutylamine
EC Number:
203-491-1
EC Name:
1,1,3,3-tetramethylbutylamine
Cas Number:
107-45-9
Molecular formula:
C8H19N
IUPAC Name:
2,4,4-trimethylpentan-2-amine

Test animals

Species:
mouse
Strain:
other: OF1
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: IFFA Credo, Domaine des Oncins, Saint-Germain sur l´Abresle, France
- Weight at study initiation: 20-25 g
- Housing: groups of 10
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: housed for 7 days under controlled environmental conditions, brought to laboratory at least 1 day before each experiment

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Exposures were conducted in a 200 L stainless steel chamber, adjustable air flow 10-30 m3/h. Vapour was generated by passing air through liquid amines and diluting with further air before entry into the exposure chamber.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
RP-HPLC following derivatisation to m-toluol derivatives
Duration of exposure:
60 - 120 min
Concentrations:
6, 8, 17 and 24 ppm
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
Upper airway irritation:
The breathing frequency was used as an index of upper respiratory tract irritation. Mice were restrained in a body plethysmograph while the head was enclosed in the inhalation chamber. Breath frequency measured with a pressure transducer before and during the 60 min exposure period. For each concentration the maximum decrease in respiratory rate occuring during the first 15 min was recorded. 4 concentrations were tested.

Pulmonary toxicity:
An intratracheal exposure was carried out in anaesthetised mice (pentobarbital, i.p.). Respiratory rate was measured in animals after recovery from anaesthesia for 75 min. Respiratory rate was monitored prior and during an 120 min exposure period.
Statistics:
Differences in the respiratory rates: student´s t-test for paired data (level of significance P<0.05);
RD50, RD50TC and RD50TC/RD50: analysis as a function of the partition coefficients of the corresponding amines with least-squares linear regression

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
other: RD50
Effect level:
80 ppm
Exp. duration:
60 min
Clinical signs:
other: In uncannulated mice: rapid onset of response maximum around 1 min. After the 60 min exposure period recovery was only partial for t-octylamin treated mice (30 min recovery time). In cannulated mice bradypnoea developed slower (15-60 min).

Any other information on results incl. tables

The more lipophilic the amine, the higher was the sensory irritation potential for upper and lower airways
(intratracheal exposure was conducted to study effects on the lower airways).

With inhalation exposure the RD50 was 80 ppm, with intratracheal exposure it amounted to 96 ppm.

Applicant's summary and conclusion

Conclusions:
In this pulmonary irritation study in the mouse a RD50 value of 80 ppm was found following exposure to vapours of the test item for 60 minutes.