3-aminopropylmethylamine

Endpoint summary

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

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 or test system 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

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.