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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEL was estimated to be 160 mg/kg bw when Wistar male and female rats were orally exposed with (3-aminopropyl)(methyl)amine.

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
Data is predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
- Name of test material: (3-aminopropyl)(methyl)amine
- 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:
Wistar
Details on species / strain selection:
not specifiednot specified
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Remarks on MMAD:
not specified
Vehicle:
water
Details on exposure:
not specified
Details on mating procedure:
not specified
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Male: 30 days
Female : 49 days
Frequency of treatment:
Daily
Details on study schedule:
not specified
Dose / conc.:
160 mg/kg bw/day
No. of animals per sex per dose:
10 animals
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified
Parental animals: Observations and examinations:
not specified
Oestrous cyclicity (parental animals):
not specified
Sperm parameters (parental animals):
not specified
Litter observations:
not specified
Postmortem examinations (parental animals):
not specified
Postmortem examinations (offspring):
not specified
Statistics:
not specified
Reproductive indices:
not specified
Offspring viability indices:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
not specified
Dose descriptor:
NOAEL
Effect level:
160 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive function (oestrous cycle)
reproductive function (sperm measures)
Remarks on result:
other: No effect observed
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
not specified
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Primary amines AND Secondary amines by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Narcotic Amine by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, NH2 group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group All Aqueous Solubility < 0.00002 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Similarity boundary:Target: CNCCCN
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.46

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.18

Conclusions:
NOAEL was estimated to be 160 mg/kg bw when Wistar male and female rats were orally exposed with (3-aminopropyl)(methyl)amine.
Executive summary:

In an prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for (3-aminopropyl)(methyl)amine. The NOAEL was estimated to be 160 mg/kg bw when Wistar male and female rats were orally exposed with (3-aminopropyl)(methyl)amine.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
160 mg/kg bw/day
Study duration:
subchronic
Species:
cat
Quality of whole database:
Data is klimisch 2 and from OECD QSAR toolbox 3.3
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Reproductive toxicity:

In different studies, (3-aminopropyl)(methyl)amine has been investigated for Reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for (3-aminopropyl)(methyl)amine along with the study available on structurally similar read across substance 2-Butanone oxime/Ethyl methyl ketone oxime (CAS no 96-29-7) and 2-Methylaminoethanol (CAS no 109-83-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In an prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for (3-aminopropyl)(methyl)amine. The NOAEL was estimated to be 160 mg/kg bw when Wistar male and female rats were orally exposed with (3-aminopropyl)(methyl)amine.

In another experimental study conducted by Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation (J-CHECK, 2010) on structurally similar read across 2-Butanone oxime/Ethyl methyl ketone oxime (CAS no 96-29-7), Crj:CD(SD) male and female rats were treated with 2-Butanone oxime/Ethyl methyl ketone oxime in the concentration of 0, 10, 30 and 100 mg/kg bw orally by gavage. No adverse effects on survival, general condition, and body weight or food consumption throughout the administration period were observed in P and F1 generation treated rats as compared to control. Similarly, No effect on reproductive performance of treated P male rats were observed as compared to control. But, significant decrease in delivery index of P female rats were observed at 100 mg/kg bw as compared to control. Significant increase in liver weights in males and heart weights in females were observed at 100 mg/kg bw as compared to control. Significant increase spleen weights of male and female rats were observed at 30 and 100 mg/kg bw as compared to control. In addition, Black and enlargement of spleen were observed in male and female rats at 30 and 100 mg/kg as compared to control. In histopathological examination, Congestion, deposition of pigment and extramedullary hematopoiesis in the spleen, deposition of glycogen, deposition of pigment in Kupffer cells and extramedullary hematopoiesis in the liver and deposition of brown pigment in the kidney were observed in male and female rats at 10, 30 and 100 mg/kg. No effects on clinical sign and body weight were observed in treated offspring. Therefore, NOAEL was considered to be 100 mg/kg bw for male rat and 30 mg/kg bw for female rats and 100 mg/kg bw for F1 generation when Crj:CD(SD) male and female rats were treated with 2-Butanone oxime/Ethyl methyl ketone oxime orally by gavage.

This is further supported by experimental study conducted by Nelson et al (Environmental Health Perspectives, Vol. 57, pp. 261-271, 1984) on structurally similar read across 2-Methylaminoethanol (CAS no 109-83-1), Sprague-Dawley female rats were exposed with 2-Methylaminoethanol in t he concentration of 0 and 150 mg/L vaporized for 7 hr/day for 28 days. No effect on clinical signs, body weight and food consumption of treated female rats were observed as compared to control. Similarly, No reproductive effect were observed such as chenage in Number pregnant/number mated, Number of Implants, Resorptions and total live fetuses were observed at 150 mg/L as compared to control. In addition, o effect on number of live fetuses, fetal weights and visceral or skeletal effect were observed in treated fetuses at 150 mg/L as compared to control. Therefore, NOAEC was considered to be 150 mg/L P and F1 generation when Sprague-Dawley female rats were exposed with 2-Methylaminoethanol by inhalation for 28 days.

 

Thus, based on the above studies and predictions on (3-aminopropyl)(methyl)amine and its read across substances, it can be concluded that NOAEL value is 160 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (3-aminopropyl)(methyl)amine can be classified as Not Classified of reproductive toxicity.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the above studies and predictions on (3-aminopropyl)(methyl)amine and its read across substances, it can be concluded that NOAEL value is 160 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (3-aminopropyl)(methyl)amine can be classified as Not Classified of reproductive toxicity.