Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from NTRL.

Data source

Reference
Reference Type:
secondary source
Title:
Initial submission: Letter from Eastman Kodak Co to USEPA Regarding Basictoxicity of 3-methylaminopropylamine with Attachments and Cover Letter dated 9/4/92.
Author:
NTRL
Year:
1992
Bibliographic source:
OTS0555335, NTRL, dated 9/4/92

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: As mention beow
Principles of method if other than guideline:
To evaluate the toxic potential of 3-methylaminopropylamine in rats by inhalation for 13 days, 6 hour /day.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material : (3-aminopropyl)(methyl)amine; 3-Amino-1-methylaminopropane
- Molecular formula : C4H12N2
- Molecular weight : 88.1528 g/mol
- Smiles notation : N(CCCN)C
- InChl : 1S/C4H12N2/c1-6-4-2-3-5/h6H,2-5H2,1H3
- Substance type: Organic
- Physical state: Liquid
Specific details on test material used for the study:
- Name of test material : (3-aminopropyl)(methyl)amine; 3-Amino-1-methylaminopropane
- Molecular formula : C4H12N2
- Molecular weight : 88.1528 g/mol
- Smiles notation : N(CCCN)C
- InChl : 1S/C4H12N2/c1-6-4-2-3-5/h6H,2-5H2,1H3
- Substance type: Organic
- Physical state: Liquid

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
7.2 µm
Geometric standard deviation (GSD):
1.41
Details on inhalation exposure:
Details on inhalation exposure
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Animals were exposed in stainless steel and glass inhalation chambers having an effective animal exposure volume of 420 liters. Atmospheres were produced by passing air over the surface of the liquid contained in a three necked flask maintained at 35° C tor 61 mg/m and 50° C for 189.3, mg/m3 . Vapor laden air exiting the flask vas diluted at a T at which point a chemical or physical reaction occurred resulting in the production of an aerosol. Particle size analysis was done by using a Royco Analyzer over the course or exposure resulted
in a stable distribution with an aerodynamic mass median diameter of 7.2µm and geometric standard deviation of 1.41.
TEST ATMOSPHERE
- Brief description of analytical method used: Approximately82% of the particles was less than 10 um in diameter. Chamber concentrations were determined every 0.5 hour by gas chromatography of sample collected in midget impingers.
- Samples taken from breathing zone: yes
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
using gas chromatography
Duration of treatment / exposure:
13 days
Frequency of treatment:
Single exposure for 6 hour/day
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/m³ air
Dose / conc.:
61 mg/m³ air
Dose / conc.:
189.3 mg/m³ air
No. of animals per sex per dose:
Total 12 animals
0.0 mg/m3- four rats
61.0 mg/m3 - four rats
189.3mg/m3- four rats
Control animals:
yes, concurrent vehicle
Details on study design:
Details on study design
Dose were selected from preliminary study

Examinations

Observations and examinations performed and frequency:
Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT:

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified

- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified


OPHTHALMOSCOPIC EXAMINATION: Not specified


HAEMATOLOGY: Not specified


CLINICAL CHEMISTRY: Not specified


URINALYSIS: Not specified


NEUROBEHAVIOURAL EXAMINATION: Not specified


OTHER:
Sacrifice and pathology:
Sacrifice and pathology
GROSS PATHOLOGY: Yes, macroscopic examination for nasal passages, trachea and lung were observed.
HISTOPATHOLOGY: Yes, microscopic examination for nasal passages, trachea and lung were observed.
Statistics:
Not specified.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No significant change were observed at dose level of 61.0 and 189.3mg/m3 in treated group compare to control.
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant change were observed at dose level of 61.0 and 189.3mg/m3 in treated group compare to control.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No significant change were observed at dose level of 61.0 and 189.3mg/m3 in treated group compare to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
As though nasal irrttion was observ ed but no significant change were observed at dose level of 61.0 and 189.3mg/m3 in treated group compare to control.
Histopathological findings: neoplastic:
not specified
Details on results:
The substance is a severe irritant.

Effect levels

Dose descriptor:
NOAEL
Effect level:
189.3 mg/m³ air
Based on:
test mat.
Sex:
not specified
Basis for effect level:
clinical signs
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No significant change were observed at dose level of 61.0 and 189.3mg/m3 in treated group compare to control.

Target system / organ toxicity

Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 189.3mg/m3 for 3-methylaminopropylamine in rats by inhalation for subacute study.
Executive summary:

In a Repeated inhalation study for 3-methylaminopropylamine in rats by inhalation was observed. The animals were exposed to test material at the concentration of 0.0 , 61.0 and 189.3mg/m3for 13 days by single exposure for 6 hour/day. As no statically significant effects were observed on the clinical sign, gross pathology and histopathology of the treated animal’s other then nasal irritation. This nasal irritation is due to irritant nature of the substance .Therefore NOAEL was considered to be 189.3mg/m3 for3-methylaminopropylamine in rats by inhalation.