3-aminopropylmethylamine

Endpoint summary

Description of key information

Acute oral toxicity:

 LD50 was estimated to be 982 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with (3-aminopropyl)(methyl)amine.

Acute inhalation toxicity:

LC50 was estimated to be 11.1 mg/L when Sprague-Dawley male and female rats were exposed with (3-aminopropyl)(methyl)amine.

Acute dermal toxicity:

LD50 was estimated to be 2293.5 mg/kg bw when New Zealand White male and female rabbits were exposed with (3-aminopropyl)(methyl)amine.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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

Test type:

other: 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:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

not specified

Doses:

982 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

982 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
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 ( not "m") )  )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and "t" )  and "u" )  and ("v" and "w" )  )

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 OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-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 Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters 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 Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aliphatic azo and azoxy (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity OR Substituted n-alkylcarboxylic acids (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens OR Metalloids by Groups of elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary AND Aliphatic Amine, secondary by Organic Functional groups ONLY

Domain logical expression index: "t"

Similarity boundary:Target: CNCCCN
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Similarity boundary:Target: CNCCCN
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.66

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.352

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 was estimated to be 982 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with (3-aminopropyl)(methyl)amine.

Executive summary:

In a 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 LD50 was estimated to be 982 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with (3-aminopropyl)(methyl)amine.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

982 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: 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:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

head only

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

not specified

Concentrations:

11.1 mg/L

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

11.1 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters 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 No alert found by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "l"

Similarity boundary:Target: CNCCCN
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.15

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.79

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LC50 was estimated to be 11.1 mg/L when Sprague-Dawley male and female rats were exposed with (3-aminopropyl)(methyl)amine.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for (3-aminopropyl)(methyl)amine. The LC50 was estimated to be 11.1 mg/L when Sprague-Dawley male and female rats were exposed with (3-aminopropyl)(methyl)amine.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

11 100 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: 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:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

2293.5 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 293.5 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
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 ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and ("r" and "s" )  )

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 Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR 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 >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters 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 Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base 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 Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "j"

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 Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group CNS Surface Tension > 62 mN/m OR Exclusion rules not met OR Group All log Kow < -3.1 OR Group All Melting Point > 200 C OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Vapour Pressure < 0.001 Pa OR Group CNS log Kow < 0.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Primary and secondary aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "p"

Similarity boundary:Target: CNCCCN
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Similarity boundary:Target: CNCCCN
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.88

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.42

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2293.5 mg/kg bw when New Zealand White male and female rabbits were exposed with (3-aminopropyl)(methyl)amine.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for (3-aminopropyl)(methyl)amine. The LD50 was estimated to be 2293.5 mg/kg bw when New Zealand White male and female rabbits were exposed with (3-aminopropyl)(methyl)amine.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 293.5 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Additional information

Acute oral toxicity:

In different studies, (3-aminopropyl)(methyl)amine has been investigated for acute oral 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)aminealong with the study available on structurally similar read across substance Dimethylamine (CAS no 124-40-3) and 1,6-Hexanediamine (CAS no 124-09-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a 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 LD50 was estimated to be 982 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with (3-aminopropyl)(methyl)amine.

In another experimental study given by NTRL (OTS0555335, NTRL, dated 9/4/92), rat and mice were treated with (3-aminopropyl)(methyl)amine in the concentration of 951 mg/kg bw and 282 mg/kg bw orally. 50% mortality was observed in treated rat at 951 mg/kg bw and in mice at 282 mg/kg bw. Hematuria and blood in urine was observed in treated rats, probably resulting from the ulcerative effect of the compound. Therefore, LD50 was considered to be 951 mg/kg bw (677-1336) for rat and 282 mg/kg bw (149-536) for mice when treated with (3-aminopropyl)(methyl)amine orally.

Further supported by experimental study conducted by GmbHet al(The MAK Collection for Occupational Health and Safety, 31 JAN 2012) on structurally similar read across substance Dimethylamine (CAS no 124-40-3), rat and mice were treated with Dimethylamine in the basic concentration of 689 mg/kg bw and 316 mg/kg bw orally. 50% mortality was observed in treated rats at 689 mg/kg bw and in mice at 316 mg/kg bw. Therefore, LD50 was considered to be 689 mg/kg bw for rat and 316 mg/kg bw for mice when treated with Dimethylamine orally.

Again supported by experimental study given by U.S. Environmental Protection Agency (Robust Summary & Test Plans: Amine Heads Category: Robust Summary, U.S. Environmental Protection Agency, 201-14400B, April 8, 2003.) on structurally similar read across substance 1,6-Hexanediamine (CAS no 124-09-4), Crl:CD® male rats were treated with 1,6-Hexanediamine in the concentration of500, 700, 800, and 1000 mg/kg orally by gavage in corn oil and observed for 14 to 16 days. No mortality was observed at 500 mg/kg, 2 rats were died at 700 mg/kg, All deaths occurred within 1 day after dosing. 7 rats were died at 800 mg/kg, All deaths occurred within 2 days after dosing and 8 rats were died at 1000 mg/kg, All deaths occurred within 1 day after dosing. Weakness, stained and wet perineal area, stained face and congestion were observed at 500 mg/kg bw, Weakness, stained and wet perineal area, stained face, diarrhea, congestion and alopecia were observed at 700 mg/kg bw, Weakness, lacrimation, stained and/or wet perineal area, stained face, pallor, diarrhea and chromodacryorrhea were observed at 800 mg/kg bw and Weakness, stained and/or wet perineal area and stained face were observed at 1000 mg/kg bw. Slight weight loss were observed in treated male rat at 500 and 700 mg/kg bw, slight to moderate weight loss were observed in treated male rat at 800 mg/kg bw and moderate weight loss were observed in treated male rat at 1000 mg/kg bw. Therefore, LD50 was considered to be 792 mg/kg bw (704-896) when Crl:CD® male rat were treated with1,6-Hexanediamine orally by gavage.

Thus, based on the above studies and predictions on (3-aminopropyl)(methyl)amine and its read across substances, it can be concluded that LD50 value is less than 982 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (3-aminopropyl)(methyl)amine can be classified a Classified in Category IV of acute oral toxicity.

Acute inhalation toxicity:

In different studies, (3-aminopropyl)(methyl)amine has been investigated for acute inhalation 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 Dimethylamine (CAS no 124-40-3) and n-Butylamine (CAS no 109-73-9. The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for (3-aminopropyl)(methyl)amine. The LC50 was estimated to be 11.1 mg/L when Sprague-Dawley male and female rats were exposed with (3-aminopropyl)(methyl)amine.

In another experimental study given by NTRL (OTS0555335, NTRL, dated 9/4/92), rat were exposed with 3-aminopropylmethylamine in the concentration of 0.0, 0.61 and 189.3 mg/m3by Whole body inhalation for 6 hours.No mortality observed at189.3 mg/m3. Therefore, LC50 was considered to be > 189.3 mg/m3when rat was exposed with3-aminopropylmethylamineby Whole body inhalation for 6 hours.

Further supported by experimental study given by U.S. National Library of Medicine (ChemIDplus, A TOXNET DATABASE, Lite Browse Advanced, 2017) and U.S. environmental protection agency (EPA/ 600/8-90/038F, September 1990) on structurally similar read across substance Dimethylamine (CAS no 124-40-3), Fischer 344 male rat were exposed with Dimethylamine in the concentration of 400, 600, 1000, 2500 to 6000 and 6119 mg/L by head only inhalation for 6 hours and observed for 48 hours. 50 % mortality observed at 4540 mg/L. Eye irritation, gasping and secretion of bloody mucus from nose, sever nasal congestion at 4000 mg/L and corneal edema at 1000 mg/L were observed in treated male rats. Ulcerative rhinitis and necrosis of turbinates at 4000 mg/L, emphysema, bronchial hyperplasia and pneumonitis at 1000 mg/L, mild emplhysema in peripheral areas of lung at 600 mg/L and fatty degeneration and focal necrosis of liver and corneal ulceration, keratitis, edema, and loss of descemets membrane at 2500 to 6000 mg/L were observed in treated male rats. Therefore, LC50 was considered to be 4540 mg/L (4208-4899) when Fischer 344 male rat was exposed with Dimethylamine by inhalation for 6 hours.

Again this is supported by experimental study given by European Commission (European Commission – European Chemicals Bureau, 18–FEB–2000) on structurally similar read across substance n-Butylamine (CAS no 109-73-9), rat were exposed with n-Butylamine in the concentration of 4.2 mg/l by inhalation for 4 hours. 50 % mortality observed at 4.2 mg/l. Therefore, LC50 was considered to be 4.2 mg/l when rat was exposed with n-Butylamine by inhalation for 4 hours.

Thus, based on the above studies and predictions on (3-aminopropyl)(methyl)amine and its read across substances, it can be concluded that LC50 value is less than 20000 mg/m³. Thus, comparing this value with the criteria of CLP regulation, (3-aminopropyl)(methyl)amine can be classified a Classified in Category IV of acute inhalation toxicity.

Acute dermal toxicity:

In different studies, (3-aminopropyl)(methyl)amine has been investigated for acute dermal 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 rabbits and rats for (3-aminopropyl)(methyl)amine along with the study available on structurally similar read across substance2–methylaminoethanol (CAs no 109-83-1) and Diisopropanolamine (CAS no 110-97-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for (3-aminopropyl)(methyl)amine. The LD50 was estimated to be 2293.5 mg/kg bw when New Zealand White male and female rabbits were exposed with (3-aminopropyl)(methyl)amine.

In another experimental study given by NTRL (OTS0555335, NTRL, dated 9/4/92), Guinea pigs were exposed with 3-aminopropylmethylamine in the concentration of84.4 to 844 mg/kg on Clipped backs of abdomen by occlusive wrapping for 24 hours. Two animals were died after 24 hours. Necroses and hemorrhage were observed in treated Guinea pigs. Severe erythema was observed in treated Guinea pigs. No skin sensitization was observed in treated Guinea pigs.Therefore, LD50 was considered to be>844 mg/kg when Guinea pigs were exposed with3-aminopropylmethylamineonClipped backs of abdomen by occlusive wrapping for 24 hours.

Further supported by experimental study given by European Commission (European Commission – European Chemicals Bureau, 18–FEB–2000) on structurally similar read across substance2–methylaminoethanol (CAs no 109-83-1),rat were exposed with 2–methylaminoethanol in the concentration of 2000 mg/kg dermaly. No mortality observed at 2000 mg/kg. Therefore, LD50 was considered to be>2000 mg/kg when rat were exposed with 2–methylaminoethanol dermally.

Again this is supported by experimental study given by OECD SIDS (US/ICCA, SIAM 29, 20-22 October 2009 ) on structurally similar read across substanceDiisopropanolamine (CAS no 110-97-4), rabbits were exposed with Diisopropanolamine in the concentration of 8000 mg/kg dermaly for 24 hours. 50 % mortality observed at 8000 mg/kg. Therefore, LD50 was considered to be 8000 mg/kg when rabbits were exposed with Diisopropanolamine dermaly for 24 hours.

Thus, based on the above studies and predictions on (3-aminopropyl)(methyl)amine and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/Kg bw. Thus, comparing this value with the criteria of CLP regulation, (3-aminopropyl)(methyl)amine can be classified a Classified in Category V of acute dermal toxicity.

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 (3-aminopropyl)(methyl)amine. is toxic by oral and inhaltion and non toxic by dermal route. Thus, comparing this with the criteria of CLP regulation, (3-aminopropyl)(methyl)amine can be classified a Classified in Category IV of acute oral and inhalation and no Classifed for dermal toxicity.