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Administrative data

Description of key information

Repeated oral

Subacute toxicity study was performed by NTRL (Source: OTS0555335, 1992) to determine the oral toxic nature of 3-methylaminopropylamine IUPAC name; 3-Amino-1-methylaminopropane (6291-84-5). In a Repeated dose study for3-methylaminopropylamine in rats by oral gavages. The animals were exposed to 12 dosage daily at the concentration of 0,10 and 50 mg/kg bw/day for 16 days. As no statically significant effects were observed on the clinical sign, food intake, body weight, Haematology, clinical chemistry, gross pathology and histopathology of the treated male and female rats compare to control. Therefore NOAEL was considered to be 50 mg/kg/day for3-methylaminopropylamine in rats by oral gavage for 16 days study.

Repeated inhalation

Subacute toxicity study was performed by NTRL (Source: OTS0555335, 1992) to determine the inhalation toxic nature of3-methylaminopropylamine IUPAC name; 3-Amino-1-methylaminopropane (6291-84-5). 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/m3 for 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 NOAEC was considered to be 189.3mg/m3 for3-methylaminopropylamine in rats by inhalation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from NTRL
Qualifier:
according to
Guideline:
other: As mention below
Principles of method if other than guideline:
To evaluate the toxic potential of 3-methylaminopropylamine in rats by oral gavage for 16 days.
GLP compliance:
not specified
Limit test:
no
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
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Not specified.
Route of administration:
oral: gavage
Details on route of administration:
Not specified.
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 and 50 mg/kg/day
Duration of treatment / exposure:
16 days
Frequency of treatment:
12 exposure
Dose / conc.:
0 other: mg/kg bw/day
Dose / conc.:
10 other: mg/kg bw/day
Dose / conc.:
50 other: mg/kg bw/day
No. of animals per sex per dose:
Total no 15
0 mg/kg/day bw;5 rats
10 mg/kg/day bw;5 rats
50mg/kg/day bw;5 rats
Control animals:
yes, concurrent vehicle
Details on study design:
Not specified.
Observations and examinations performed and frequency:
Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

Mortality: not specified

BODY WEIGHT: Yes


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: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available.

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: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available

OPHTHALMOSCOPIC EXAMINATION: No data available

HAEMATOLOGY: Yes
- Parameters checked in table [No.?] were examined.- Haemoglobin , haematocrits and White blood cell
Counts (neutrophil and monocyte) were observed.

CLINICAL CHEMISTRY: Yes
- Parameters checked in table [No.?] were examined. - Glutamic oxaloacetic transaminase, lactic dehydrogenase, urea nitrogen, alkaline phosphatase, glucose and glutamic pyruvic transaminase were observed.

URINALYSIS: No data available.

NEUROBEHAVIOURAL EXAMINATION: No data available.

Other; Absolute and relative liver and kidney weight were observed.
Sacrifice and pathology:
Sacrifice and pathology
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Statistics:
Yes,Mean± Standard deviation was observed.
Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
No statically significant effects were observed at dose level of 10 and 50 mg/kg bw/day in treated group compare to control.
Mortality:
not specified
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
As though there was slight decrease in the body weight but no statically significant effects were observed at dose level of 10 and 50 mg/kg bw/day in treated group compare to control.
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Description (incidence and severity):
As though there was slight decrease in the food intake but no statically significant effects were observed at dose level of 10 and 50 mg/kg bw/day in treated group compare to control.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
No statically significant effects were observed at dose level of 10 and 50 mg/kg bw/day in treated group compare to control.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
No statically significant effects were observed at dose level of 10 and 50 mg/kg bw/day in treated group compare to control.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
No statically significant effects were observed at dose level of 10 and 50 mg/kg bw/day in treated group compare to control.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
No statically significant effects were observed at dose level of 10 and 50 mg/kg bw/day in treated group compare to control.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, non-treatment-related
Description (incidence and severity):
No statically significant effects were observed at dose level of 10 and 50 mg/kg bw/day in treated group compare to control.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Dose descriptor:
NOAEL
Effect level:
50 other: mg/kg/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
body weight and weight gain
food consumption and compound intake
haematology
clinical biochemistry
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No significant effects were observed on the clinical sign, food intake, body weight, Haematology, clinical chemistry, gross pathology and histopathology.
Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Organ weight

Dose

50 mg/kg/day

Organ

liver

kidney

Absolute

N

N

Relative

N

N

Dose

10 mg/kg/day

Absolute

N

N

Relative

N

N

Conclusions:
NOAEL was considered to be 50 mg/kg/day for 3-methylaminopropylamine in rats by oral gavage for 16 days study.
Executive summary:

In a Repeated dose study for 3-methylaminopropylamine in rats by oral gavage. The animals were exposed to 12 dosage daily at the concentration of 0,10 and 50 mg/kg bw/day for 16 days. As no statically significant effects were observed on the clinical sign, food intake, body weight, Haematology, clinical chemistry, gross pathology and histopathology of the treated male and female rats compare to control. Therefore NOAEL was considered to be 50 mg/kg/day for3-methylaminopropylamine in rats by oral gavage for 16 days study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Data is from NTRL

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
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.
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
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
Species:
rat
Strain:
not specified
Sex:
not specified
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
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
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.
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.
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.
Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
189.3 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
Data is from NTRL

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose oral toxicity:

Various experimental studies were reviewed to determine the toxic nature of 3-Amino-1-methylaminopropane Other name; 3-methylaminopropylamine (6291-84-5) upon repeated exposure by oral route. The studies are as mentioned below:

Subacute toxicity study was performed by NTRL (Source: OTS0555335, 1992) to determine the oral toxic nature of 3-methylaminopropylamine IUPAC name; 3-Amino-1-methylaminopropane (6291-84-5). In a Repeated dose study for3-methylaminopropylamine in rats by oral gavages. The animals were exposed to 12 dosage daily at the concentration of 0,10 and 50 mg/kg bw/day for 16 days. As no statically significant effects were observed on the clinical sign, food intake, body weight, Haematology, clinical chemistry, gross pathology and histopathology of the treated male and female rats compare to control. Therefore NOAEL was considered to be 50 mg/kg/day for3-methylaminopropylamine in rats by oral gavage for 16 days study.

Another Subacute toxicity study was performed by NTRL (Source: OTS0555335, 1992) to determine the oral toxic nature of3-methylaminopropylamine IUPAC name; 3-Amino-1-methylaminopropane Other name (6291-84-5). In a Repeated dose study for3-methylaminopropylamine in rats by oral gavage.

In a Repeated dose study for3-methylaminopropylamine in rats by oral gavage. The animals were exposed to 13 dosage daily at the concentration of 0,100 and 500 mg/kg bw/day for 17 days.One animal out of five died at the dose level of 100 mg/kg/day in treated animal compare to control. The animal which died on day seven, survived all 13 exposure.One animal produced labored breathing at the dose level of 500 mg/kg/day in treated group compare to control.Statically significant decrease in the food intake and body weight weight was observed at the dose group of 100 and 500 mg/kg/day in treated group compare to control.The absolute liver and kidney weights were moderately reduced at both dose levels. In the 500 mg/kg/day group, glutamic oxaloacetic Transaminase, lactic dehydrogenase, urea nitrogen, and glucose were slightly elevated while alkaline phosphatase and glutamic pyruvic transaminase were normal compare to control. In the 500 mg/kg/day group, glutamic oxaloacetic Transaminase, lactic dehydrogenase, urea nitrogen, and glucose were slightly elevated while alkaline phosphatase and glutamic pyruvic transaminase were normal compare to control.Microscopic examination revealed significant changes at both dose level .Due to the corrosive activity, no site of toxic action could be identified. Therefore LOAEL was considered to be 100 mg/kg/day for 3-methylaminopropylamine in rats by oral gavage for 17 days study.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by U. S. National Library of Medicine (Pubmed.Food Chem Toxicol. 1997 Mar-Apr;35(3-4):337-48, 2017)to determine the mutagenic nature of Putrescine (110-60-1). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance.

A repeated dose toxicity study for Putrescine (110-60-1) was conducted in Wistar male and female rats for six week.The test material was exposed by oral feed at the concentration of 0,20,180and 500 mg/kg/day. The animals were observed forclinical sign, body weight, Food and water consumption, Hematology, clinical chemistry, gross pathology and hitopathology. Significant changes were observed at the highest dose (500 mg/kg/day). Therefore NOAEL was considered to be 180 mg/kg/day inWistar male and female rats by oral feed for 6weeks study.

 

The data available for the target chemical 3-Amino-1-methylaminopropane Other name; 3-methylaminopropylamine (6291-84-5) and its read across as well as applying weight of evidence is insufficient to classify the chemical as toxic. Also the NOAEL value range can be close to 50 mg/kg bw/day in males and females. Based on the observations made3-Amino-1-methylaminopropane does not exhibit toxicity upon repeated exposure by oral route. Hence the test chemical is not likely to classify as a toxicant upon repeated exposure by oral route. Further testing is required to clearly judge the test chemical as toxic upon repeated exposure.

Repeated inhalation study:

Experimental studies were reviewed to determine the toxic nature of 3-Amino-1-methylaminopropane Other name; 3-methylaminopropylamine (6291-84-5) upon repeated exposure by inhalation route. The studies are as mentioned below:

Subacute toxicity study was performed by NTRL (Source: OTS0555335, 1992) to determine the inhalation toxic nature of3-methylaminopropylamine IUPAC name; 3-Amino-1-methylaminopropane (6291-84-5). In a Repeated inhalation study for3-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 NOAEC was considered to be 189.3mg/m3 for3-methylaminopropylamine in rats by inhalation.

The data available for the target chemical 3-Amino-1-methylaminopropane ;Other name; 3-methylaminopropylamine (6291-84-5) is insufficient to classify the chemical as toxic. Also the NOAEL value range can be close to 189.3mg/m3 in males and females. Based on the observations made3-Amino-1-methylaminopropane does not exhibit toxicity upon repeated exposure by inhalation route. Hence the test chemical is not likely to classify as a toxicant upon repeated exposure by inhalation route. Further testing is required to clearly judge the test chemical as toxic upon repeated exposure.

Repeated dermal study

The study need not be conducted because the substance is classified as corrosive to the skin .The experimental pH of (3-aminopropyl)(methyl)amine (CAS No: 6291-84-5) is 13.5. Hence the end point was taken as waiver.

 

 

 

 

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, 3-Amino-1-methylaminopropane Other name; 3-methylaminopropylamine (6291-84-5) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.